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2023 Male Fertility Studies

FertileFacts lists all of the 2023 Male Fertility studies to date. We update this list frequently, so check back soon!
PMIDTitleAbstractPublication DateAuthorsURL
38639588[Protective effect of vitrification and controlled slow freezing on immature testicular tissue].To explore and compare the current mainstream testicular tissue freezing methods, namely vitrification and controlled slow freezing, and optimize the best testicular tissue freezing methods.2023Ma MH, Su WL, Lü LY, Chen HC, Fang C, Sun P, Liu GH
38620126Seminal fluid changes in the COVID-19 era: During infection and Post-vaccination.Coronavirus disease 2019 (COVID-19) predilection for angiotensin-converting enzyme 2 (ACE2) receptors allows its entrance and replication; however, they are not biochemically required for viral fusion into the cell membrane. Testicular tissue has abundant ACE2 receptors, making it a target for the COVID-19 virus. Seminal fluid parameters are measures of male fertility. Changes in semen parameters have been caused by coronavirus disease and vaccines. Some attribute that effect to direct hematogenic spread to the testis; others propose that the excessive immunological response triggered by the infection causes a deleterious effect. An unsubstantiated claim questioned whether the SARS-CoV-2 vaccine could trigger an unintentional immunological response that would impair male fertility once receiving the vaccine. Extensive research confirms the transient nature of those changes that affect sperm motility and count with full recovery post-COVID-19 infection and after vaccination. The vaccine’s safety was reaffirmed; however, there are currently no recommendations for screening sperm donors. Research is warranted to guarantee the safety of couples undergoing assisted reproduction.2023Nori W, Akeel Salman D
38619413[Effects of urogenital mycoplasma and chlamydial infections on male fertility].ObjectiveÔºö This study aimed to assess the impact of urogenital ureaplasma urealyticum (Uu), Mycoplasma hominis (Mh), and Chlamydia trachomatis (Ct) infections on semen quality in men.MethodsÔºö In this study, 1022 males were enrolled at the Department of Reproductive Medicine, Rizhao People’s Hospital, Shandong Province from October 2014 to January 2023. The participants included 393 in the infertility group, 139 in the recurrent miscarriage group, and 490 in the control group. Based on age, 852 cases were < 36 years old, and 170 cases were ‚â• 36 years old. All patients underwent routine semen analysis and tests for Uu, Mh, and Ct, with results statistically analyzed for their impact on semen quality and compared among different age groups. Results: Among the 1022 patients, 344 (33.6%) were Uu-positive, 49 (4.7%) were Mh-positive, and 31 (3.0%) were Ct positive. The sperm concentration, total sperm count, forward sperm motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate of Uu Mh and/or Ct-positive patients were significantly lower than those of the negative group, and the overall difference between the two groups was statistically significant (P<0.05). The positive rate of Uu infection was 41.7% in the infertility group, 30.2% in the recurrent miscarriage group and 28.2% in the control group, and the overall positive rate of the three groups was statistically significant(P<0.05). The positive rate of Mh infection was 6.9% in the infertility group, 8.6% in the recurrent miscarriage group and 2.0% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positive rate of Ct infection was 6.1% in the infertility group, 2.9% in the recurrent miscarriage group and 0.6% in the control group, and the overall positive rate of the three groups was statistically significant (P<0.001). The positivity rate of Uu infection was 35.8% at the age of <36 years and 22.9% at the age ‚â• 36 years, and there was a statistically significant difference in the positivity rate between the two groups (P<0.05). Conclusion: The prevalence of Uu infection in the male urogenital tract is significantly higher than that of Mh and Ct, which is the main pathogen of urogenital tract infection in men. Uu, Mh and Ct infections have adverse effects on sperm concentration, total sperm count, sperm forward motility rate (PR), sperm motility rate (PR+NP) and normal sperm morphology rate, which will lead to a decrease in semen quality and affect male fertility. Genital tract infections are closely related to age, and the prevalence of Uu infection is higher in the younger age group.2023Li M, Hu CX, Lu XL, Yu LH, Xu XM, Wang XF, Tan SN, Gong XL, Xing SC
38602764[Research progress on the correlation between gut microbiota and male infertility].Male infertility is one of the serious problems currently affecting human reproduction and health. Healthy gut microbiota is involved in the development of the immune system and protection against pathogen invasion, and it maintain normal metabolism and improve reproductive potential by secreting a variety of substances. The imbalance of gut microbiota can promote the local and systemic immune inflammatory response, induce chronic metabolic diseases, affect the synthesis of sex hormones, cause abnormal spermatogenesis, maturation or activation, and it is closely related to the decline of male fertility. By exploring the correlation between gut microbiota and male infertility, this paper aims to provide new clues and directions for the clinical diagnosis and treatment of male infertility.2023Sun X, Cheng P, Zang GH
38515820Preservation of male fertility in patients undergoing pelvic irradiation.As the number of cancer survivors increases, so does the demand for preserving male fertility after radiation. It is important for healthcare providers to understand the pathophysiology of radiation-induced testicular injury, the techniques of fertility preservation both before and during radiation, and their role in counseling patients on the risks to their fertility and the means of mitigating these risks. Impaired spermatogenesis is a known testicular toxicity of radiation in both the acute and the late settings, as rapidly dividing spermatogonial germ cells are exquisitely sensitive to irradiation. The threshold for spermatogonial injury and subsequent impairment in spermatogenesis is ~ 0.1 Gy and the severity of gonadal injury is highly dose-dependent. Total doses < 4 Gy may allow for recovery of spermatogenesis and fertility potential, but with larger doses, recovery may be protracted or impossible. All patients undergoing gonadotoxic radiation therapy should be counseled on the possibility of future infertility, offered the opportunity for semen cryopreservation, and offered referral to a fertility specialist. In addition to this, every effort should be made to shield the testes (if not expected to contain tumor) during therapy.2023Ramirez-Fort MK, Kardoust-Parizi M, Flannigan R, Bach P, Koch N, Gilman C, Suarez P, Fort DV, McClelland S, Lange CS, Mulhall JP, Fort M, Schlegel PN
38496251Characterization of genomic regions escaping epigenetic reprogramming in sheep.The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the pre-implantation embryo after fertilization. These events involve the erasure and re-establishment of DNA methylation marks. However, imprinted genes and transposable elements (TEs) maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species. Therefore, the objective of this study was to examine the characteristics and locations of genomic regions that evade epigenetic reprogramming in sheep, as well as to explore the biological functions of the genes within these regions. In a previous study, we identified 107 transgenerationally inherited differentially methylated cytosines (DMCs) in the F1 and F2 generations in response to a paternal methionine-supplemented diet. These DMCs were found in TEs, non-repetitive regions, and imprinted and non-imprinted genes. Our findings suggest that genomic regions, rather than TEs and imprinted genes, have the propensity to escape reprogramming and serve as potential candidates for transgenerational epigenetic inheritance. Notably, 34 transgenerational methylated genes influenced by paternal nutrition escaped reprogramming, impacting growth, development, male fertility, cardiac disorders, and neurodevelopment. Intriguingly, among these genes, 21 have been associated with neural development and brain disorders, such as autism, schizophrenia, bipolar disease, and intellectual disability. This suggests a potential genetic overlap between brain and infertility disorders. Overall, our study supports the concept of transgenerational epigenetic inheritance of environmentally induced marks in mammals.2024Braz CU, Passamonti MM, Khatib H
38481407Sixth edition of the World Health Organization laboratory manual of semen analysis: Updates and essential take away for busy clinicians.Semen analysis is the cornerstone for male fertility evaluation. In 2021, the World Health Organization (WHO) released its 62024Chung E, Atmoko W, Saleh R, Shah R, Agarwal A
38469506Dichotomous sperm in Lepidopteran insects: a biorational target for pest management.Lepidoptera are unusual in possessing two distinct kinds of sperm, regular nucleated (eupyrene) sperm and anucleate (apyrene) sperm (‘parasperm’). Sperm of both types are transferred to the female and are required for male fertility. Apyrene sperm play ‘helper’ roles, assisting eupyrene sperm to gain access to unfertilized eggs and influencing the reproductive behavior of mated female moths. Sperm development and behavior are promising targets for environmentally safer, target-specific biorational control strategies in lepidopteran pest insects. Sperm dimorphism provides a wide window in which to manipulate sperm functionality and dynamics, thereby impairing the reproductive fitness of pest species. Opportunities to interfere with spermatozoa are available not only while sperm are still in the male (before copulation), but also in the female (after copulation, when sperm are still in the male-provided spermatophore, or during storage in the female’s spermatheca). Biomolecular technologies like RNAi, miRNAs and CRISPR-Cas9 are promising strategies to achieve lepidopteran pest control by targeting genes directly or indirectly involved in dichotomous sperm production, function, or persistence.2023Seth RK, Yadav P, Reynolds SE
38370539Heat stress reveals a fertility debt owing to postcopulatory sexual selection.Climates are changing rapidly, demanding equally rapid adaptation of natural populations. Whether sexual selection can aid such adaptation is under debate; while sexual selection should promote adaptation when individuals with high mating success are also best adapted to their local surroundings, the expression of sexually selected traits can incur costs. Here we asked what the demographic consequences of such costs may be once climates change to become harsher and the strength of natural selection increases. We first adopted a classic life history theory framework, incorporating a trade-off between reproduction and maintenance, and applied it to the male germline to generate formalized predictions for how an evolutionary history of strong postcopulatory sexual selection (sperm competition) may affect male fertility under acute adult heat stress. We then tested these predictions by assessing the thermal sensitivity of fertility (TSF) in replicated lineages of seed beetles maintained for 68 generations under three alternative mating regimes manipulating the opportunity for sexual and natural selection. In line with the theoretical predictions, we find that males evolving under strong sexual selection suffer from increased TSF. Interestingly, females from the regime under strong sexual selection, who experienced relaxed selection on their own reproductive effort, had high fertility in benign settings but suffered increased TSF, like their brothers. This implies that female fertility and TSF evolved through genetic correlation with reproductive traits sexually selected in males. Paternal but not maternal heat stress reduced offspring fertility with no evidence for adaptive transgenerational plasticity among heat-exposed offspring, indicating that the observed effects may compound over generations. Our results suggest that trade-offs between fertility and traits increasing success in postcopulatory sexual selection can be revealed in harsh environments. This can put polyandrous species under immediate risk during extreme heat waves expected under future climate change.2024Baur J, Zwoinska M, Koppik M, Snook RR, Berger D
38322636Use of Anabolic-Androgenic Steroids and Male Fertility: A Systematic Review and Meta-analysis.Anabolic-androgenic steroids (AASs) are often used by men for bodybuilding and to improve sports performance. The use is not limited to professional competitive athletes, but many amateur men.2023Mulawkar PM, Maheshwari PN, Gauhar V, Agrawal SG, Mohammed TO, Singh AG, Tak GR, Shah US, Shukla DP, Mamankar D
38322633Explaining the Unexplained: Examining the Predictive Value of Semen Parameters, Sperm DNA Fragmentation and Metal Levels in Unexplained Infertility.There is ongoing research to find an optimum modality to predict male fertility potential.2023Ghuman NK, Shukla KK, Nandagopal S, Raikar S, Kumar S, Kathuria P, Choudhary D, Elhence P, Singh P
38303979Bioactive compounds as potential alternative treatments to prevent cancer therapy-induced male infertility.About 8-12% of couples experience infertility, with male infertility being the cause in 50% of cases. Several congenital and acquired conditions, including chronic diseases and their treatments, can contribute to male infertility. Prostate cancer incidence increases annually by roughly 3%, leading to an increment in cancer treatments that have adverse effects on male fertility. To preserve male fertility post-cancer survival, conventional cancer treatments use sperm cryopreservation and hormone stimulation. However, these techniques are invasive, expensive, and unsuitable in prepubertal patients lacking mature sperm cells. Alternatively, nutritional therapies enriched with bioactive compounds are highlighted as non-invasive approaches to prevent male infertility that are easily implementable and cost-effective. In fact, curcumin and resveratrol are two examples of bioactive compounds with chemo-preventive effects at the testicular level. In this article, we summarize and discuss the literature regarding bioactive compounds and their mechanisms in preventing cancer treatment-induced male infertility. This information may lead to novel opportunities for future interventions.2023Simón L, Mariotti-Celis MS
38303402Exposure to particulate matter may affect semen quality via trace metals: Evidence from a retrospective cohort study on fertile males.Particulate matter (PM) exposure may be associated with male semen quality. Besides, PM exposure induces up and down levels of trace metals in tissues or organs. The levels of trace metals in semen are critical for adverse male semen quality. This study aims to evaluate the concentrations of seminal-level trace metals in fertile men and assess its associations with PM exposure and to explore the mediation role of trace metals in seminal plasma plays in the relationship between PM exposure and semen quality. Total 1225 fertile men who participated in a cohort study from 2014 to 2016 were finally recruited. Multivariate linear regression was applied to explore associations between each two of PM exposure, trace metals and semen parameters. 1-year PM2024Cheng Y, Zhu J, Tang Q, Wang J, Feng J, Zhou Y, Li J, Pan F, Han X, Lu C, Wang X, Langston ME, Chung BI, Wu W, Xia Y
38283528Uncovering the Association Between Complete AZFc Microduplications and Spermatogenic Ability: The First Reported Series.Purpose This article aims to report the first series of men with complete2023Asanad K, Greenfeld E, Scherer SW, Yuen R, Marshall CR, Lo K, Mullen B, Lau S, Jarvi KA, Samplaski MK
38276265Bridging the Gap: Animal Models in Next-Generation Reproductive Technologies for Male Fertility Preservation.This review aims to explore advanced reproductive technologies for male fertility preservation, underscoring the essential role that animal models have played in shaping these techniques through historical contexts and into modern applications. Rising infertility concerns have become more prevalent in human populations recently. The surge in male fertility issues has prompted advanced reproductive technologies, with animal models playing a pivotal role in their evolution. Historically, animal models have aided our understanding in the field, from early reproductive basic research to developing techniques like artificial insemination, multiple ovulation, and in vitro fertilization. The contemporary landscape of male fertility preservation encompasses techniques such as sperm cryopreservation, testicular sperm extraction, and intracytoplasmic sperm injection, among others. The relevance of animal models will undoubtedly bridge the gap between traditional methods and revolutionary next-generation reproductive techniques, fortifying our collective efforts in enhancing male fertility preservation strategies. While we possess extensive knowledge about spermatogenesis and its regulation, largely thanks to insights from animal models that paved the way for human infertility treatments, a pressing need remains to further understand specific infertility issues unique to humans. The primary aim of this review is to provide a comprehensive analysis of how animal models have influenced the development and refinement of advanced reproductive technologies for male fertility preservation, and to assess their future potential in bridging the gap between current practices and cutting-edge fertility techniques, particularly in addressing unique human male factor infertility.2023Aponte PM, Gutierrez-Reinoso MA, Garcia-Herreros M
38274996Human-specific epigenomic states in spermatogenesis.Infertility is becoming increasingly common, affecting one in six people globally. Half of these cases can be attributed to male factors, many driven by abnormalities in the process of sperm development. Emerging evidence from genome-wide association studies, genetic screening of patient cohorts, and animal models highlights an important genetic contribution to spermatogenic defects, but comprehensive identification and characterization of the genes critical for male fertility remain lacking. High divergence of gene regulation in spermatogenic cells across species poses challenges for delineating the genetic pathways required for human spermatogenesis using common model organisms. In this study, we leveraged post-translational histone modification and gene transcription data for 15,491 genes in four mammalian species (human, rhesus macaque, mouse, and opossum), to identify human-specific patterns of gene regulation during spermatogenesis. We combined H3K27me3 ChIP-seq, H3K4me3 ChIP-seq, and RNA-seq data to define epigenetic states for each gene at two stages of spermatogenesis, pachytene spermatocytes and round spermatids, in each species. We identified 239 genes that are uniquely active, poised, or dynamically regulated in human spermatogenic cells distinct from the other three species. While some of these genes have been implicated in reproductive functions, many more have not yet been associated with human infertility and may be candidates for further molecular and epidemiologic studies. Our analysis offers an example of the opportunities provided by evolutionary and epigenomic data for broadly screening candidate genes implicated in reproduction, which might lead to discoveries of novel genetic targets for diagnosis and management of male infertility and male contraception.2024Liao C, Walters BW, DiStasio M, Lesch BJ
38264086Nomograms for Predicting Postoperative Sperm Improvements in Varicocele Patients.Varicocele is a condition that seriously affects male fertility. It can cause pathological changes in the testicles and affect their spermatogenesis and endocrine function.2024Maimaitiming A, Muhemaiti A, Mulati Y, Li X
38260159Exploring the evolving function of soluble intercellular adhesion molecule-1 in junction dynamics during spermatogenesis.Intercellular adhesion molecule-1 (ICAM-1) is a transmembrane glycoprotein expressed on immune, endothelial, and epithelial cells. Its ectodomain can be proteolytically cleaved to release a circulating soluble form called sICAM-1. Clinical studies demonstrate sICAM-1 is upregulated in various diseases and associated with disease severity. Research has identified sICAM-1 as a regulator of the blood-testis barrier (BTB) and spermatogenesis. Overexpression of sICAM-1 weakened the BTB2023Xiao X, Han Y, Li Q, Zheng D, Cheng CY, Ni Y
38260147Impact of stress on male fertility: role of gonadotropin inhibitory hormone.Studies have implicated oxidative stress-sensitive signaling in the pathogenesis of stress-induced male infertility. However, apart from oxidative stress, gonadotropin inhibitory hormone (GnIH) plays a major role. The present study provides a detailed review of the role of GnIH in stress-induced male infertility. Available evidence-based data revealed that GnIH enhances the release of corticosteroids by activating the hypothalamic-pituitary-adrenal axis. GnIH also mediates the inhibition of the conversion of thyroxine (T4) to triiodothyronine (T3) by suppressing the hypothalamic-pituitary-thyroidal axis. In addition, GnIH inhibits gonadotropin-releasing hormone (GnRH), thus suppressing the hypothalamic-pituitary-testicular axis, and by extension testosterone biosynthesis. More so, GnIH inhibits kisspeptin release. These events distort testicular histoarchitecture, impair testicular and adrenal steroidogenesis, lower spermatogenesis, and deteriorate sperm quality and function. In conclusion, GnIH, via multiple mechanisms, plays a key role in stress-induced male infertility. Suppression of GnIH under stressful conditions may thus be a beneficial prophylactic and/or therapeutic strategy.2023Odetayo AF, Akhigbe RE, Bassey GE, Hamed MA, Olayaki LA
38256311Impact of GLP-1 Agonists on Male Reproductive Health-A Narrative Review.2023Varnum AA, Pozzi E, Deebel NA, Evans A, Eid N, Sadeghi-Nejad H, Ramasamy R
38250327Steroid hormone signaling: multifaceted support of testicular function.Embryonic development and adult physiology are dependent on the action of steroid hormones. In particular, the reproductive system is reliant on hormonal signaling to promote gonadal function and to ensure fertility. Here we will describe hormone receptor functions and their impacts on testicular function, focusing on a specific group of essential hormones: androgens, estrogens, progesterone, cortisol, and aldosterone. In addition to focusing on hormone receptor function and localization within the testis, we will highlight the effects of altered receptor signaling, including the consequences of reduced and excess signaling activity. These hormones act through various cellular pathways and receptor types, emphasizing the need for a multifaceted research approach to understand their critical roles in testicular function. Hormones exhibit intricate interactions with each other, as evidenced, for example, by the antagonistic effects of progesterone on mineralocorticoid receptors and cortisol’s impact on androgens. In light of research findings in the field demonstrating an intricate interplay between hormones, a systems biology approach is crucial for a nuanced understanding of this complex hormonal network. This review can serve as a resource for further investigation into hormonal support of male reproductive health.2023Matsuyama S, DeFalco T
38247463Impact of Chromium Picolinate on Leydig Cell Steroidogenesis and Antioxidant Balance Using an In Vitro Insulin Resistance Model.Leydig cells (LCs) play a pivotal role in male fertility, producing testosterone. Chromium (III) picolinate (CrPic2023Moreira R, Martins AD, Ferreira R, Alves MG, Pereira ML, Oliveira PF
38234819PNLDC1 catalysis and postnatal germline function are required for piRNA trimming, LINE1 silencing, and spermatogenesis in mice.PIWI-interacting RNAs (piRNAs) play critical and conserved roles in transposon silencing and gene regulation in the animal germline. Two distinct piRNA populations are present during mouse spermatogenesis: pre-pachytene piRNAs in fetal/neonatal testes and pachytene piRNAs in adult testes. PNLDC1 is required for both pre-pachytene piRNA and pachytene piRNA 3′ end maturation in multiple species. However, whether PNLDC1 is the bona fide piRNA trimmer and the physiological role of 3′ trimming of two distinct piRNA populations in spermatogenesis remain unclear. Here, by inactivating2023Wei C, Yan X, Mann JM, Geng R, Xie H, Demireva EY, Sun L, Ding D, Chen C
38203631The Role of microRNA in Spermatogenesis: Is There a Place for Fertility Preservation Innovation?Oncological treatments have dramatically improved over the last decade, and as a result, survival rates for cancer patients have also improved. Quality of life, including concerns about fertility, has become a major focus for both oncologists and patients. While oncologic treatments are often highly effective at suppressing neoplastic growth, they are frequently associated with severe gonadotoxicity, leading to infertility. For male patients, the therapeutic option to preserve fertility is semen cryopreservation. In prepubertal patients, immature testicular tissue can be sampled and stored to allow post-cure transplantation of the tissue, immature germ cells, or in vitro spermatogenesis. However, experimental techniques have not yet been proven effective for restoring sperm production for these patients. MicroRNAs (miRNAs) have emerged as promising molecular markers and therapeutic tools in various diseases. These small regulatory RNAs possess the unique characteristic of having multiple gene targets. MiRNA-based therapeutics can, therefore, be used to modulate the expression of different genes involved in signaling pathways dysregulated by changes in the physiological environment (disease, temperature, ex vivo culture, pharmacological agents). This review discusses the possible role of miRNA as an innovative treatment option in male fertility preservation-restoration strategies and describes the diverse applications where these new therapeutic tools could serve as fertility protection agents.2023Klees C, Alexandri C, Demeestere I, Lybaert P
38203468Lipidomic Profile of Human Sperm Membrane Identifies a Clustering of Lipids Associated with Semen Quality and Function.Reduced sperm motility and/or count are among the major causes of reduced fertility in men, and sperm membranes play an important role in the spermatogenesis and fertilization processes. However, the impact of sperm lipid composition on male fertility remains under-investigated. The aim of the present study was to perform a lipidomic analysis of human sperm membranes: we performed an untargeted analysis of membrane lipid composition in fertile (N = 33) and infertile subjects (N = 29). In parallel, we evaluated their serum lipid levels. Twenty-one lipids were identified by their mass/charge ratio and post-source decay spectra. Sulfogalactosylglycerolipid (SGG, seminolipid) was the most abundant lipid component in the membranes. In addition, we observed a significant proportion of PUFAs. Important differences have emerged between the fertile and infertile groups, leading to the identification of a lipid cluster that was associated with semen parameters. Among these, cholesterol sulfate, SGG, and PUFAs represented the most important predictors of semen quality. No association was found between the serum and sperm lipids. Dietary PUFAs and SGG have acknowledged antioxidant functions and could, therefore, represent sensitive markers of sperm quality and testicular function. Altogether, these results underline the important role of sperm membrane lipids, which act independently of serum lipids levels and may rather represent an independent marker of reproductive function.2023Di Nisio A, De Toni L, Sabovic I, Vignoli A, Tenori L, Dall’Acqua S, Sut S, La Vignera S, Condorelli RA, Giacone F, Ferlin A, Foresta C, Garolla A
38202747Mechanistic Insights into Peptide Binding and Deactivation of an Adhesion G Protein-Coupled Receptor.Adhesion G protein-coupled receptors (ADGRGs) play critical roles in the reproductive, neurological, cardiovascular, and endocrine systems. In particular, ADGRG2 plays a significant role in Ewing sarcoma cell proliferation, parathyroid cell function, and male fertility. In 2022, a cryo-EM structure was reported for the active ADGRG2 bound by an optimized peptide agonist IP15 and the Gs protein. The IP15 peptide agonist was also modified to antagonists 4PH-E and 4PH-D with mutations of the 4PH residue to Glu and Asp, respectively. However, experimental structures of inactive antagonist-bound ADGRs remain to be resolved, and the activation mechanism of ADGRs such as ADGRG2 is poorly understood. Here, we applied Gaussian accelerated molecular dynamics (GaMD) simulations to probe conformational dynamics of the agonist- and antagonist-bound ADGRG2. By performing GaMD simulations, we were able to identify important low-energy conformations of ADGRG2 in the active, intermediate, and inactive states, as well as explore the binding conformations of each peptide. Moreover, our simulations revealed critical peptide-receptor residue interactions during the deactivation of ADGRG2. In conclusion, through GaMD simulations, we uncovered mechanistic insights into peptide (agonist and antagonist) binding and deactivation of the ADGRG2. These findings will potentially facilitate rational design of new peptide modulators of ADGRG2 and other ADGRs.2023Adediwura VA, Miao Y
38198791Obesity and Male Infertility: True, True, and Unrelated?While the prevalence of obesity has rapidly increased worldwide, there has also been a notable decline in semen parameters over the last several decades. While obesity can negatively impact reproductive hormones, many studies have sought a link between rising obesity and decreased male fertility potential. Nonetheless, few data support a direct link between the two. The focus on obesity as a causative factor in male infertility can potentially result in patient harm through delayed fertility treatment and missed diagnoses. This review investigates the associations between obesity and male infertility and why a potential direct link has been elusive and may not exist. Additionally, indirect mechanisms that may link the two will be reviewed and treatment options for obese infertile men presenting for evaluation will briefly be discussed.2023Ceraolo C, Rubano A, Gabrielsen JS
38185017Predictive characteristics of male fertility in alpacas with special reference to seminal NGF.Recent studies document the LH-releasing pathway of nerve growth factor (NGF) in male camelids and that the LH response to seminal NGF is associated with elevated plasma testosterone concentration. Results provide rationale for the hypothesis that NGF in semen is associated with male fertility. In Experiment 1, the association between the amount of NGF in the ejaculate and characteristics of the male reproductive system was examined in alpacas. The concentration of NGF was measured by radioimmunoassay in semen samples collected from male alpacas (n = 47) and correlated with sperm morphology and motility, and measurements of the male reproductive anatomy. Most ejaculates had NGF concentrations that, based on previous studies, triggered ovulation in female camelids, however, we only found a positive correlation between NGF concentration with sperm concentration, thread formation and total NGF, and a negative correlation with pH. In Experiment 2, a retrospective analysis was carried out to determine if breeding performance during the previous season was related to recent concentrations of seminal NGF in male alpacas (n = 22). Birth rates tended to be correlated with sperm concentration and total amount of NGF in the ejaculate (P = 0.09). Experiment 3 was a prospective study to determine the relationship between seminal NGF (n = 8 male alpacas) and ovulation and pregnancy rates in a breeding trial. No association was detected between seminal NGF concentration and ovulation rate, pregnancy rate, or LH response in the female. We conclude that among the breeding males used in our study, the abundance of seminal NGF was correlated with sperm concentration and thread formation, however, it was not predictive of male fertility in alpacas. Examination of males not previously selected as breeding stock may be expected to include a broader range of seminal NGF and provide a more comprehensive understanding of the relationship between seminal NGF and male fertility.2024Carrasco RA, Bogle OA, Ratto MH, Ulloa-Leal C, Mamani-Cato RH, Adams GP
38178948Vitamin D supplementation for improving sperm parameters in infertile men: A systematic review and meta-analysis of randomized clinical trials.Vitamin D has been hypothesized to have a potential role in altering sperm motility and metabolism. However, experimental studies have demonstrated inconsistent results between vitamin D and sperm parameters. This study aims to investigate the role of vitamin D supplementation to improve sperm parameters in infertile men.2023Tania C, Tobing ERPL, Tansol C, Prasetiyo PD, Wallad CK, Hariyanto TI
38149356Ultrastructural study:Mouse testicular tissue is composed of seminiferous tubules and interstitial tissue. Mammalian spermatogenesis is divided into three stages: spermatocytogenesis (mitotic divisions) in which spermatogonial stem cells (SSCs) turn into spermatocytes, followed by two consecutive meiotic divisions in which spermatocytes form spermatids. Spermatids differentiate into spermatozoa during spermiogenesis. Various factors affect the process of spermatogenesis and the organization of cells in the testis. Any disorder in different stages of spermatogenesis will have negative effects on male fertility. The aim of the current study was to compare the2024Bashiri Z, Movahedin M, Pirhajati V, Asgari H, Koruji M
38142451[Fertility preservation of adult and prepubertal male cancer patients].No Abstract2023Vesztergom D, Takács T, Bíró K, Polgár C, Krádi A, Varga S, Novák Z, Kopa Z
38138881Semen Cryopreservation to Expand Male Fertility in Cancer Patients: Intracase Evaluation of Semen Quality.To preserve male fertility after diagnosis of any kind of cancer, a prompt assessment of the semen quality and an appropriate semen cryopreservation must be performed before radio-chemotherapy starts. The present work aims to evaluate the semen parameters at diagnosis of different cancer patients before cryopreservation and after thawing. Testicular tumors and lymphomas are among the most common cancers in younger patients, and while chemotherapy significantly increases patients’ survival, it can epigenetically alter the semen fluid, resulting in temporary or permanent infertility. We analyzed data from the database of the Gamete Cryopreservation Center (Annunziata Hospital, CS; Italy) in the period of 2011-2020 from a cohort of 254 cancer patients aged 18-56 years. The evaluation was performed in a blind manner and anonymously recovered; the main parameters referring to semen quality were assessed in accordance with the WHO guidelines and decision limits (6th edition; 2021). The cancer types were as follows: testis cancers (TC;2023Peluso G, Tisato V, Singh AV, Gemmati D, Scarpellini F
38136796A Single-Step Genome-Wide Association Study for Semen Traits of Egyptian Buffalo Bulls.The present study aimed to contribute to the limited research on buffalo (2023El Nagar AG, Salem MMI, Amin AMS, Khalil MH, Ashour AF, Hegazy MM, Abdel-Shafy H
38126735The seminal odorant binding protein Obp56g is required for mating plug formation and male fertility inIn2023Brown NC, Gordon B, McDonough-Goldstein CE, Misra S, Findlay GD, Clark AG, Wolfner MF
38123054Fluorene-9-bisphenol exposure damages the testis in mice through a novel mechanism of ferroptosis.Fluorene-9-bisphenol (BHPF) is an emerging global endocrine-disrupting chemical found in numerous household products as a substitute of bisphenol A. Many studies have reported various toxicities associated with BHPF. However, the effect of BHPF on male reproduction, particularly on the structural integrity of the blood testis barrier (BTB) in mice, has not yet been extensively studied. Ferroptosis, a newly identified form of cell death, occurs in the testicular tissue following exposure to BPA, affecting male fertility. We investigated whether ferroptosis plays a role in BHPF-induced testicular damage. The findings indicated that BHPF exposure led decreases in serum testosterone (T) concentration and sperm concentration and motility in mice. Furthermore, BHPF disrupted the BTB by interfering with key BTB-related proteins, including Cx43, β-catenin, and ZO-1. Moreover, BHPF induced ferroptosis through the induction of lipid peroxidation, iron overload, oxidative stress, and mitochondrial dysfunction in the testicular tissue. Inhibition of ferroptosis using Fer-1 mitigated the BHPF-induced damage to the BTB and ferroptosis in TM4 cells. Overall, our findings indicated the detrimental effects of BHPF on male reproductive function in mice, suggesting ferroptosis as a mechanism underlying testicular damage.2024Feng Q, Liu Y, Zou L, Lei M, Zhu C, Xia W
38116206Development of a biomolecular approach to identify sperm functions and fertility using sperm RNAs.Infertility affects a significant percentage of couples worldwide, and male factors contribute significantly to this problem. Traditional assessments of male fertility rely primarily on parameters such as sperm motility, morphology, viability, and concentration. However, these metrics often do not provide a comprehensive understanding of sperm function, which is critical not only for fertilization but also for successful embryo development. Herein, we used porcine spermatozoa as a model to investigate the potential of sperm RNA markers in assessing various aspects of sperm function from motility to fertility. Using artificial insemination, we evaluated male fertility based on the litter size of sows inseminated with sperm from 20 boars. In addition, we measured parameters such as weaning rate, death births, live births, and mummy births. Sperm functional parameters, including motility and kinematics, were assessed before and after2023Pang WK, Park YJ, Pang MG
38114777The Role of Chlorella vulgaris in Attenuating Infertility Induced by Cadmium Chloride via Suppressing Oxidative Stress and Modulating Spermatogenesis and Steroidogenesis in Male Rats.Cadmium (Cd) is an environmental pollutant known as endocrine disruptor . Cd has been reported to induce perturbations of the testicular functions and the subsequent decline of the male fertility of both animals and humans. Chlorella vulgaris (ChV) a species of green microalga has been reported to have multiple beneficial activities such as anti-inflammatory, antioxidant, and antiapoptotic effects. Thus, this work was conducted to declare the benefits of Chlorella vulgaris (ChV) (500 mg/kg doses) against cadmium chloride CdCl2024Farag MR, El-Naseery NI, El Behery EI, Nouh DS, El-Mleeh A, Mostafa IMA, Alagawany M, Di Cerbo A, Azzam MM, Mawed SA
38114454Gss deficiency causes age-related fertility impairment via ROS-triggered ferroptosis in the testes of mice.Glutathione synthetase (GSS) catalyzes the final step in the synthesis of glutathione (GSH), a well-established antioxidant. Research on the specific roles of the Gss gene during spermatogenesis remains limited due to the intricate structure of testis. In this study, we identified pachytene spermatocytes as the primary site of GSS expression and generated a mouse model with postnatal deletion of Gss using Stra8-Cre (S8) to investigate the role of GSS in germ cells. The impact of Gss knockout on reducing male fertility is age-dependent and caused by ferroptosis in the testis. The 2-month-old S8/Gss2023Zhu H, Cheng Y, Wang X, Yang X, Liu M, Liu J, Liu S, Wang H, Zhang A, Li R, Ye C, Zhang J, Gao J, Fu X, Wu B
38111663 Thousands of genes are expressed in the testis of mice. However, the details about their roles during spermatogenesis have not been well-clarified for most genes. The purpose of this study was to examine the effect of2023Meng Z, Qiao Y, Xue J, Wu T, Gao W, Huang X, Lv J, Liu M, Shen C
38101758Enhanced clearance of C. muridarum infection using azithromycin-loaded liposomes.Chlamydia trachomatis is an intracellular bacterium which infects around 129 million people annually. Despite similar infection rates between sexes, most research investigating the effects of chlamydial infection on fertility has focused on females. There is now emerging evidence of a potential link between Chlamydia and impaired male fertility. The only treatments for chlamydial infection are antibiotics, with azithromycin (AZI) being one of the commonly used drugs. However, recent studies have suggested that optimizing the treatment regime is necessary, as higher concentrations of AZI may be required to effectively clear the infection in certain cell types, particularly testicular macrophages. To address this challenge, we have prepared liposomes consisting of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) loaded with AZI for clearing Chlamydia. These liposomes exhibited stability over time and were readily taken up by both macrophages and epithelial cells. Moreover, they demonstrated significant enhancement of chlamydial clearance in both cell types. In a mouse model, the drug-loaded liposomes cleared Chlamydia within the penile urethra more efficiently than the same dose of unencapsulated drug. Furthermore, the liposome-drug treatment showed significant protective effects on sperm motility and morphology, suggesting potential benefits in reducing sperm damage caused by the infection.2024Arasu Y, Bryan E, Russell FA, Huettner N, Carey AJ, Boyd BJ, Beagley KW, Dargaville TR
38101699Food, nutrition, and fertility: from soil to fork.Food and nutrition-related factors, including foods and nutrients consumed, dietary patterns, use of dietary supplements, adiposity, and exposure to food-related environmental contaminants, have the potential to impact semen quality and male and female fertility; obstetric, fetal, and birth outcomes; and the health of future generations, but gaps in evidence remain. On 9 November 2022, Tufts University’s Friedman School of Nutrition Science and Policy and the school’s Food and Nutrition Innovation Institute hosted a 1-d meeting to explore the evidence and evidence gaps regarding the relationships between food, nutrition, and fertility. Topics addressed included male fertility, female fertility and gestation, and intergenerational effects. This meeting report summarizes the presentations and deliberations from the meeting. Regarding male fertility, a positive association exists with a healthy dietary pattern, with high-quality evidence for semen quality and lower quality evidence for clinical outcomes. Folic acid and zinc supplementation have been found to not impact male fertility. In females, body weight status and other nutrition-related factors are linked to nearly half of all ovulation disorders, a leading cause of female infertility. Females with obesity have worse fertility treatment, pregnancy-related, and birth outcomes. Environmental contaminants found in food, water, or its packaging, including lead, perfluorinated alkyl substances, phthalates, and phenols, adversely impact female reproductive outcomes. Epigenetic research has found that maternal and paternal dietary-related factors can impact outcomes for future generations. Priority evidence gaps identified by meeting participants relate to the effects of nutrition and dietary patterns on fertility, gaps in communication regarding fertility optimization through changes in nutritional and environmental exposures, and interventions impacting germ cell mechanisms through dietary effects. Participants developed research proposals to address the priority evidence gaps. The workshop findings serve as a foundation for future prioritization of scientific research to address evidence gaps related to food, nutrition, and fertility.2024Maitin-Shepard M, Werner EF, Feig LA, Chavarro JE, Mumford SL, Wylie B, Rando OJ, Gaskins AJ, Sakkas D, Arora M, Kudesia R, Lujan ME, Braun J, Mozaffarian D
38100996Sperm-borne tsRNAs and miRNAs analysis in relation to dairy cattle fertility.Sperm small non-coding RNAs (sncRNAs), such as microRNAs (miRNAs) and tRNA-derived small RNAs (tsRNAs), have been found to have implications for male fertility and play a role in the intergenerational transmission of specific phenotypes by influencing the early embryo’s physiological processes in various animal species. This study postulates that there exists a correlation between sperm small non-coding RNAs (sncRNAs) and bull fertility, which in turn can influence the fertility of offspring through the modulation of early embryo development. To investigate this hypothesis, we generated comparative libraries of sperm sncRNAs from sires exhibiting high (n¬†=¬†3) versus low bull fertility (n¬†=¬†3), as well as high (n¬†=¬†3) versus low daughter fertility (n¬†=¬†3), as determined by the industry-standard Bull fertility index and Daughter fertility index. In total, 12 tsRNAs carried by sperm (11 down-regulated and 1 up-regulated) were found to be associated with bull fertility, while 19 tsRNAs (11 down-regulated and 8 up-regulated) were found to be associated with daughter fertility (q¬†<¬†0.05, Log2foldchange>¬±1.5, base mean¬†>¬†50). Notably, tRX-Glu-NNN-3811 exhibited potential as a biomarker for predicting fertility in both male and female dairy cattle. Moreover, a total of six miRNAs sperm-borne (two up-regulated and four down-regulated) and 35 miRNAs (27 up-regulated and eight down-regulated) exhibited a significant correlation with both bull fertility and daughter fertility individually (p¬†<¬†0.05, base mean¬†>¬†50, log2foldchange>¬±1.5), two microRNAs, namely miR-2385-5p (down-regulated) and miR-98 (up-regulated), exhibit a significant association (p¬†<¬†0.05, base mean¬†>¬†50, log2foldchange>¬±1.5) with the fertility of both bulls and daughter. The targets of these two microRNAs were subsequently identified and integrated with the transcriptomic database of the embryonic cells at the two-cell stage, which is known to be indicative of embryonic competence. The KEGG analysis revealed a potential correlation between these targets and choline metabolism, a crucial factor in embryonic epigenetic programming. In summary, the findings of this study indicate that sperm-borne small non-coding RNAs (sncRNAs) hold promise as biomarkers for predicting and enhancing fertility in dairy cattle. Furthermore, it is plausible that these sncRNAs may exert their effects on daughter fertility by targeting genes in the early embryo.2024Zhang Y, Labrecque R, Tremblay P, Plessis C, Dufour P, Martin H, Sirard MA
38097889Revealing the role of CCoAOMT1: fine-tuning bHLH transcription factors for optimal anther development.The tapetum, a crucial innermost layer encompassing male reproductive cells within the anther wall, plays a pivotal role in normal pollen development. The transcription factors (TFs) bHLH010/089/091 redundantly facilitate the rapid nuclear accumulation of DYSFUNCTIONAL TAPETUM 1, a gatekeeper TF in the tapetum. Nevertheless, the regulatory mechanisms governing the activity of bHLH010/089/091 remain unknown. In this study, we reveal that caffeoyl coenzyme A O-methyltransferase 1 (CCoAOMT1) is a negative regulator affecting the nuclear localization and function of bHLH010 and bHLH089, probably through their K259 site. Our findings underscore that CCoAOMT1 promotes the nuclear export and degradation of bHLH010 and bHLH089. Intriguingly, elevated CCoAOMT1 expression resulted in defective pollen development, mirroring the phenotype observed in bhlh010 bhlh089 mutants. Moreover, our investigation revealed that the K259A mutation in the bHLH089 protein disrupted its translocation from the nucleus to the cytosol and impeded its degradation induced by CCoAOMT1. Importantly, transgenic plants with the probHLH089::bHLH0892024Lai Z, Wang J, Fu Y, Wang M, Ma H, Peng S, Chang F
38094287The Ameliorative Impact of2023Fakher S, Karbalay-Doust S, Noorafshan A, Seghatoleslam A
38092793Identification of hub genes and their expression profiling for predicting buffalo (Bubalus bubalis) semen quality and fertility.Sperm transcriptomics provide insights into subtle differences in sperm fertilization competence. For predicting the success of complex traits like male fertility, identification of hub genes involved in various sperm functions are essential. The bulls from the transcriptome profiled samples (n = 21), were grouped into good and poor progressive motility (PM), acrosome integrity (AI), functional membrane integrity (FMI) and fertility rate (FR) groups. The up-regulated genes identified in each group were 87, 470, 1715 and 36, respectively. Gene networks were constructed using up- and down-regulated genes from each group. The top clusters from the upregulated gene networks of the PM, AI, FMI and FR groups were involved in tyrosine kinase (FDR = 1.61E-11), apoptosis (FDR = 1.65E-8), translation (FDR = 2.2E-16) and ribosomal pathway (FDR = 1.98E-21), respectively. From the clusters, the hub genes were identified and validated in a fresh set of semen samples (n = 12) using RT-qPCR. Importantly, the genes (fold change) RPL36AL (14.99) in AI, EIF5A (54.32) in FMI, and RPLP0 (8.55) and RPS28 (13.42) in FR were significantly (p < 0.05) up-regulated. The study suggests that the expression levels of MAPK3 (PM), RPL36AL + RPS27A or RPL36AL + EXT2 (AI), RPL36AL or RPS27A (FMI) and RPS18 + RPS28 (FR) are potential markers for diagnosing the semen quality and fertility status of bulls which can be used for the breeding program.2023Swathi D, Ramya L, Archana SS, Krishnappa B, Binsila BK, Selvaraju S
38092034Unraveling the Impact of Sperm DNA Fragmentation on Reproductive Outcomes.In recent years, there has been a growing interest in identifying subcellular causes of male infertility, and sperm DNA fragmentation (SDF) research has been at the forefront of this focus. DNA damage can occur during spermatogenesis due to faulty chromatin compaction or excessive abortive apoptosis. It can also happen as sperm transit through the genital tract, often induced by oxidative stress. There are several methods for SDF testing, with the sperm chromatin structure assay, terminal deoxynucleotidyl transferase d-UTI nick end labeling (TUNEL) assay, comet assay, and sperm chromatin dispersion test being the most commonly used. Numerous studies strongly support the negative impact of SDF on male fertility potential. DNA damage has been linked to various morphological and functional sperm abnormalities, ultimately affecting natural conception and assisted reproductive technology outcomes. This evidence-based review aims to explore how SDF influences male reproduction and provide insights into available therapeutic options to minimize its detrimental impact.2023Nielsen JLM, Majzoub A, Esteves S, Humaidan P
38089935 Activity-regulated cytoskeleton associated protein (Arc1), which is required for synaptic plasticity and metabolism in2023Gordon K, Gonzales P, Lee C, Marcin J, Takashima Y, Lazzaro B, Wolfner M
38084666CRISPR/Cas9-mediated genome editing reveals seven testis-enriched transmembrane glycoproteins dispensable for male fertility in mice.Mammalian fertilization is mediated by multiple sperm acrosomal proteins, many of which are testis-enriched transmembrane glycoproteins expressed during spermiogenesis (e.g., Izumo sperm-egg fusion 1, Sperm acrosome associated 6, and Transmembrane protein 95).2023Ogawa Y, Lu Y, Kiyozumi D, Chang HY, Ikawa M
38082221Efficient pathway for men fertility preservation in testicular cancer or lymphoma: a cross-sectional study of national 2018 data.In 15-49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15-49 years-old men diagnosed with TC or L in 2018. We designed a¬†national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15-49 years-old men diagnosed with TC or L who banked sperm.2023Prades S, Jos SL, Sa√Øas-Magnan J, Bujan L, Eustache F, Blagosklonov O, Lechevallier E, Brugnon F, Loup-Cabaniols V, Bosquet D, Prades M, Ducrocq B, Chalas C, Giscard-d’Estaing S, Mayeur A, Koscinsky I, Schmitt F, Papaxanthos-Roche A, Teletin M, Thibault E, Beauvillard D, Mirallie S, Delepine B, Benhaim A, May-Panloup P, Veau S, Frapsauce C, Fauque P, Costello R, Rives N, Metzler-Guillemain C, Perrin J
38081819Phase-separated CCER1 coordinates the histone-to-protamine transition and male fertility.Idiopathic fertility disorders are associated with mutations in various genes. Here, we report that coiled-coil glutamate-rich protein 1 (CCER1), a germline-specific and intrinsically disordered protein (IDP), mediates postmeiotic spermatid differentiation. In contrast, CCER1 deficiency results in defective sperm chromatin compaction and infertility in mice. CCER1 increases transition protein (Tnp1/2) and protamine (Prm1/2) transcription and mediates multiple histone epigenetic modifications during the histone-to-protamine (HTP) transition. Immiscible with heterochromatin in the nucleus, CCER1 self-assembles into a polymer droplet and forms a liquid-liquid phase-separated condensate in the nucleus. Notably, we identified loss-of-function (LoF) variants of human CCER1 (hCCER1) in five patients with nonobstructive azoospermia (NOA) that were absent in 2713 fertile controls. The mutants led to premature termination or frameshift in CCER1 translation, and disrupted condensates in vitro. In conclusion, we propose that nuclear CCER1 is a phase-separated condensate that links histone epigenetic modifications, HTP transitions, chromatin condensation, and male fertility.2023Qin D, Gu Y, Zhang Y, Wang S, Jiang T, Wang Y, Wang C, Chen C, Zhang T, Xu W, Wang H, Zhang K, Hu L, Li L, Xie W, Wu X, Hu Z
38077491Establishment of new convenient two-line system for hybrid production by targeting mutation ofThe two-line pollination control system, which usually depends on the utilization of thermosensitive or photoperiod genic male-sterile lines, has been widely used in various crops. However, this system is susceptible to instability issues caused by uncontrollable weather fluctuations. A stable and handy two-line pollination control system is highly desirable in many crop species for heterosis exploitation.2023Cheng H, Hao M, Sang S, Wen Y, Cai Y, Wang H, Wang W, Mei D, Hu Q
38077147The hypoxia-inducible factor EPAS1 is required for spermatogonial stem cell function in regenerative conditions.In this study we explored the role of hypoxia and the hypoxia-inducible transcription factor EPAS1 in regulating spermatogonial stem cell (SSC) function in the mouse testis. We have demonstrated that SSCs reside in hypoxic microenvironments in the testis through utilization of the oxygen-sensing probe pimonidazole, and by confirming the stable presence of EPAS1, which is degraded at >5% O2023Bernstein IR, Nixon B, Lyons JM, Damyanova KB, De Oliveira CS, Mabotuwana NS, Stanger SJ, Kaiko GE, Ying TH, Oatley JM, Skillen NM, Lochrin AJ, Peters JL, Lord T
38077127Age-related decline in spermatogenic activity accompanied with endothelial cell senescence in male mice.Male fertility decreases with aging, with spermatogenic decline being one of its causes. Altered testis environment is suggested as a cause of the phenotype; however, the associated mechanisms remain unclear. Herein, we investigated the age-related changes in testicular somatic cells on spermatogenic activity. The number and proliferation of spermatogonia significantly reduced with aging in mice. Interestingly, senescence-associated β-galactosidase-positive cells appeared in testicular endothelial cell (EC) populations, but not in germ cell populations, with aging. Transcriptome analysis of ECs indicated that senescence occurred in the ECs of aged mice. Furthermore, the support capacity of ECs for spermatogonial proliferation significantly decreased with aging; however, the senolytic-induced removal of senescent cells from aged ECs restored their supporting capacity to a comparable level as that of young ECs. Our results suggest that the accumulation of senescent ECs in the testis is a potential factor contributing to the age-related decline in spermatogenic activity.2023Ozawa M, Mori H, Endo T, Ishikawa-Yamauchi Y, Motooka D, Emori C, Ikawa M
38073308A P-type pentatricopeptide repeat protein ZmRF5 promotes 5′ region partial cleavages of atp6c transcripts to restore the fertility of CMS-C maize by recruiting a splicing factor.A fast evolution within mitochondria genome(s) often generates discords between nuclear and mitochondria, which is manifested as cytoplasmic male sterility (CMS) and fertility restoration (Rf) system. The maize CMS-C trait is regulated by the chimeric mitochondrial gene, atp6c, and can be recovered by the restorer gene ZmRf5. Through positional cloning in this study, we identified the nuclear restorer gene, ZmRf5, which encodes a P-type pentatricopeptide repeat (PPR) family protein. The over-expression of ZmRf5 brought back the fertility to CMS-C plants, whereas its genomic editing by CRISPR/Cas9 induced abortive pollens in the restorer line. ZmRF5 is sorted to mitochondria, and recruited RS31A, a splicing factor, through MORF8 to form a cleaving/restoring complex, which promoted the cleaving of the CMS-associated transcripts atp6c by shifting the major cleavage site from 480th nt to 344 th nt for fast degradation, and preserved just right amount of atp6c RNA for protein translation, providing adequate ATP6C to assembly complex V, thus restoring male fertility. Interestingly, ATP6C in the sterile line CMo17A, with similar cytology and physiology changes to YU87-1A, was accumulated much less than it in NMo17B, exhibiting a contrary trend in the YU87-1 nuclear genome previously reported, and was restored to normal level in the presence of ZmRF5. Collectively these findings unveil a new molecular mechanism underlying fertility restoration by which ZmRF5 cooperates with MORF8 and RS31A to restore CMS-C fertility in maize, complemented and perfected the sterility mechanism, and enrich the perspectives on communications between nucleus and mitochondria.2024Lin Y, Yang H, Liu H, Lu X, Cao H, Li B, Chang Y, Guo Z, Ding D, Hu Y, Xue Y, Liu Z, Tang J
38072394Calcium and vitamin D homoeostasis in male fertility.Calcium and vitamin D have well-established roles in maintaining calcium balance and bone health. Decades of research in human subjects and animals have revealed that calcium and vitamin D also have effects on many other organs including male reproductive organs. The presence of calcium-sensing receptor, vitamin D receptor, vitamin D activating and inactivating enzymes and calcium channels in the testes, male reproductive tract and human spermatozoa suggests that vitamin D and calcium may modify male reproductive function. Functional animal models have shown that vitamin D deficiency in male rodents leads to a decrease in successful mating and fewer pregnancies, often caused by impaired sperm motility and poor sperm morphology. Human studies have to a lesser extent validated these findings; however, newer studies suggest a positive effect of vitamin D supplementation on semen quality in cases with vitamin D deficiency, which highlights the need for initiatives to prevent vitamin D deficiency. Calcium channels in male reproductive organs and spermatozoa contribute to the regulation of sperm motility and capacitation, both essential for successful fertilisation, which supports a need to avoid calcium deficiency. Studies have demonstrated that vitamin D, as a regulator of calcium homoeostasis, influences calcium influx in the testis and spermatozoa. Emerging evidence suggests a potential link between vitamin D deficiency and male infertility, although further investigation is needed to establish a definitive causal relationship. Understanding the interplay between vitamin D, calcium and male reproductive health may open new avenues for improving fertility outcomes in men.2024Yahyavi SK, Boisen IM, Cui Z, Jorsal MJ, Kooij I, Holt R, Juul A, Blomberg Jensen M
38070704Development of small-molecule inhibitors that target PI3Kβ.Phosphatidylinositol-3 kinase (PI3K) β, a subtype of class I PI3Ks, has an essential role in PTEN-deficient tumors and links to thrombosis, male fertility, and Fragile X syndrome. PI3Kβ-specific targeting therapy could be an efficacious treatment for diseases highly dependent on PI3Kβ, while mitigating the severe toxicity of pan-PI3K inhibitors. Achieving selectivity can be accomplished through three primary strategies, namely, binding to the induced lipophilic pocket, targeting the unique amino acid residue of PI3Kβ, or using atropisomerism to lock conformation. In this review, we focus on advances in the development of these β-isoform-selective PI3K inhibitors, providing potential guidance for the further development of novel clinical candidates.2024Yu Y, Gu D, Cai L, Yang H, Sheng R
38070681An assessment of alterations to human sperm methylation patterns in coronavirus disease 2019 infected and healthy control males.To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects male reproductive health, considering the many potential factors that contribute to declines in male fertility on a semiglobal scale.2024Stirland I, Soares MR, Furtado CLM, Dos Reis RM, Aston KI, Smith RP, Jenkins TG
38069021Regulatory Effects of theKisspeptin, a neuropeptide encoded by the2023Shi H, Yan Z, Du H, Tang Y, Song K, Yang Q, Huang X, Wang P, Gao X, Yang J, Gun S
38068847Observational Cross-Sectional Study on Mediterranean Diet and Sperm Parameters.Infertility, affecting 15 to 25% of couples in the most developed countries, is recognized by the World Health Organization as a public health issue at a global level. Different causes are acknowledged to reduce fertility in both sexes. In particular, about 40-50% of cases recognize a male factor. Dietary habits and lifestyle are acknowledged to influence sperm quality and are therefore important modifiable factors in male reproductive health. Conditions such as overweight/obesity, impaired glucose metabolism and determinants of metabolic syndrome, together with unhealthy lifestyle behavior, i.e., smoking cigarettes and physical inactivity, are suggested to have a negative impact on male fertility. While individual elements and characteristics of the Western diet and habits are considered risk factors for male infertility, the Mediterranean diet (MD) seems to promote reproductive potential for improving sperm quality. It is also interesting to note that previous observational studies reported a positive correlation between the consumption of the single food classes of the MD pattern (i.e., vegetables and fruits, poultry, fish and seafood, whole grains, low-fat dairy products) and the quality of several sperm parameters. To evaluate the relationship between sperm parameters and MD adherence, we performed a cross-sectional study on the seminal data of 300 males (mean age 34.6 ± 9.1 years) who spontaneously referred to our center of reproductive medicine. The evaluation of adherence to MD was performed with a validated 14-point Mediterranean Diet Adherence Screener (MEDAS) questionnaire. Our findings showed that sperm parameters such as sperm count, motility, viability and normal morphology are significantly and positively correlated with MEDAS, independently of BMI and age. In addition, the application of an ROC curve on MEDAS value vs. seminal alterations identified 6.25 as the score threshold value below which altered sperm parameters were more likely to occur [AUC = 0.096 (CI: 0.059-0.133;2023Petre GC, Francini-Pesenti F, Di Nisio A, De Toni L, Grande G, Mingardi A, Cusmano A, Spinella P, Ferlin A, Garolla A
38065885Restoration of reproductive capacity in a male patient with congenital adrenal hyperplasia and bilateral testicular adrenal rest tumors (TARTs) after six months of glucocorticoid intensification: A case report.Congenital adrenal hyperplasia (CAH) is considered one of the most common inherited disorders. In about more than 95% of all CAH cases, the deficient enzyme is 21-hydroxylase. Infertility is an important complication of this disease, and although this topic has been studied more frequently in females, cases, and literature reviews of the causes of infertility in male patients are constantly increasing.2023Ahmad J, Ahmad A, Hadid L
38054786Role of Eruca sativa L. seeds in boosting the reproductive performance of male Japanese quails (Coturnix c. japonica).Herein we attempt to shed light on the potential improving effect of Eruca sativa seeds (ESS) on the reproductive aspects of male Japanese quails. To accomplish this objective, two groups of quails were supplemented with ESS powder at doses of 5 and 10‚Äâg/kg feed from 7 days to 140 days of age, in addition to the control group, which did not receive treatment. Forty males were reared singly in cages to evaluate sperm characters and 32 males were raised with 64 females to evaluate fertility and sperm penetrability. Sixty-six phytochemical compounds were found according to gas chromatography-mass spectrometry analysis of ESS. The most plentiful ones are 13-docosenoic acid methyl ester, 9-octadecenoic acid methyl ester, and linoleic acid methyl ester. Both 5‚Äâg/kg and 10‚Äâg/kg doses of ESS showed similar effectiveness in enhancing various reproductive parameters, including gonadal index, sperm characteristics, fertility, libido, and cloacal gland attributes. However, some aspects like sperm concentration and testosterone levels exhibited a dose-dependent response. There is no significant change in mortality rate of supplemented groups compared to the control one. ESS also caused a reduction in feed intake and an enhancement in feed conversion ratio without affecting final body weight and body weight gain. This suggests potential nutritional benefits beyond reproductive health. The low-dose-fed group showed a significant reduction in total cholesterol and malondialdehyde compared to the high-dose-fed and unfed groups. The higher dose notably increased total antioxidant capacity compared to the lower dose and control group. Despite the positive effects on male reproductive parameters, there wasn’t a significant impact on hatchability percentage, indicating that while male fertility improved, it might not have directly affected the viability of the eggs. Overall, the study suggests that ESS could be a safe and promising addition to the diet of male Japanese quails to enhance their reproductive capabilities without adverse effects. The findings could have implications for poultry farming by potentially improving breeding efficiency and health outcomes in quails.2024Waly HSA, Abdelfattah MG, Abou Khalil NS, Ragab SMM
38052218Sulforaphane attenuates irradiation induced testis injury in mice.The testis is vulnerable to ionizing radiation, sexual dysfunction and male infertility are common problems after local radiation or whole-body exposure. Currently, there are no approved drugs for the prevention or treatment of radiation testicular injury. Sulforaphane (SFN) is an indirect antioxidant that induces phase II detoxification enzymes and antioxidant genes. Herein, we investigated the radiation protective effect of SFN on testicular injury in mice and its potential mechanism.2023Ran Y, Duan N, Gao Z, Liu Y, Liu X, Xue B
38048348SPSL1 is essential for spermatophore formation and sperm activation in Spodoptera frugiperda.The reproductive process in various species has undergone evolutionary adaptations at both the physiological and molecular levels, playing a significant role in maintaining their populations. In lepidopteran insects, the spermatophore is a unique structure formed in the female reproductive system, in which sperm storage and activation take place. It is known that the formation of the spermatophore is regulated by seminal fluid proteins derived from males. However, studies investigating the genetic mechanisms behind spermatophore formation in lepidopterans have been limited. In this study, our focus was on SPSL1, a gene that encodes a trypsin-type seminal fluid protein in Spodoptera frugiperda, a pest species with global invasive tendencies. Our findings revealed that SPSL1 expression was predominantly observed in the male reproductive tracts, and the disruption of this gene resulted in male sterility. Surprisingly, fluorescence analysis indicated that the absence of SPSL1 did not affect spermatogenesis or sperm migration within the male reproductive system. However, when females mated with SPSL1-mutant males, several defects were observed. These included disruptions in spermatophore formation, sperm activation in the copulatory bursae, and sperm migration into the spermathecae. Additionally, mass spectrometry analysis highlighted reduced levels of energy-related metabolites, suggesting that SPSL1 plays an essential role in promoting hydrolysis reactions during copulation. Consequently, our study demonstrates that SPSL1 is crucial for male fertility due to its functions in spermatophore formation and sperm activation. This research provides valuable insights into the genetic factors underlying reproductive processes in lepidopteran insects and sheds light on potential strategies for controlling invasive pest populations.2023Qian L, Yang X, Xu X, Yang D, Zhu C, Yi M, Bi H, Wang Y, Huang Y
38044573Single-cell transcriptome characteristics of testicular terminal epithelium lineages during aging in the Drosophila.Aging is a complex biological process leading to impaired functions, with a variety of hallmarks. In the testis of Drosophila, the terminal epithelium region is involved in spermatid release and maturation, while its functional diversity and regulatory mechanism remain poorly understood. In this study, we performed single-cell RNA-sequencing analysis (scRNA-seq) to characterize the transcriptomes of terminal epithelium in Drosophila testes at 2-, 10 and 40-Days. Terminal epithelium populations were defined with Metallothionein A (MtnA) and subdivided into six novel sub-cell clusters (EP0-EP5), and a series of marker genes were identified based on their expressions. The data revealed the functional characteristics of terminal epithelium populations, such as tight junction, focal adhesion, bacterial invasion, oxidative stress, mitochondrial function, proteasome, apoptosis and metabolism. Interestingly, we also found that disrupting genes for several relevant pathways in terminal epithelium led to male fertility disorders. Moreover, we also discovered a series of age-biased genes and pseudotime trajectory mediated state-biased genes during terminal epithelium aging. Differentially expressed genes during terminal epithelium aging were mainly participated in the regulation of several common signatures, e.g. mitochondria-related events, protein synthesis and degradation, and metabolic processes. We further explored the Drosophila divergence and selection in the functional constraints of age-biased genes during aging, revealing that age-biased genes in epithelial cells of 2‚ÄâDays group evolved rapidly and were endowed with greater evolutionary advantages. scRNA-seq analysis revealed the diversity of testicular terminal epithelium populations, providing a gene target resource for further systematic research of their functions during aging.2024Chen X, Qi Y, Huang Q, Sun C, Zheng Y, Ji L, Shi Y, Cheng X, Li Z, Zheng S, Cao Y, Gu Z, Yu J
38042436Adverse effects of exposure to petrol-generator exhaust fumes on the reproductive hormones, testis and spermatozoa in male dogs.There is evidence that sperm count has progressively declined in men over the recent decades. Exposure to air pollutants including petrol and diesel exhaust have been reported to impair male reproduction although there is little experimental evidence. This study investigated the effects of petrol-generator exhaust fumes (PGEF) on semen, sperm, gonadal structure and hormonal status in the dog. Sixteen adult male Basenji dogs were randomly assigned four to each of 4 groups as follows: an unexposed (Control) group and three groups exposed to graded levels of PGEF for 1, 2 or 3 h per day (hpd), respectively, for 90 days. Serum concentrations of testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured on days 0 (baseline), 30, 60 and 90 of the study. At day 90, semen samples were collected for semen and sperm analysis. Testicular and epididymal tissues were subjected to gross, histopathological and histomorphometric evaluation. Graded exposure to PGEF resulted in increased serum concentration of T and decreased concentrations of FSH and LH, increased seminal plasma lipid peroxidation, seminiferous and epididymal tubular degeneration, germ cell depletion, lowered sperm concentration, decreased sperm motility and vitality, and increased sperm abnormal morphology. The close proximity between dogs and humans in exposed environments underscores the importance of these findings to human reproductive health and fertility. The findings suggest that with prolonged exposure, the impairment of reproductive functions will likely play significant roles in the decline in male fertility.2024Oguejiofor CF, Eze UU, Eke IG, Eze AA, Onyejekwe OB, Anene BM
38038747CCDC146 is required for sperm flagellum biogenesis and male fertility in mice.Multiple morphological abnormalities of the flagella (MMAF) is a severe disease of male infertility, while the pathogenetic mechanisms of MMAF are still incompletely understood. Previously, we found that the deficiency of Ccdc38 might be associated with MMAF. To understand the underlying mechanism of this disease, we identified the potential partner of this protein and found that the coiled-coil domain containing 146 (CCDC146) can interact with CCDC38. It is predominantly expressed in the testes, and the knockout of this gene resulted in complete infertility in male mice but not in females. The knockout of Ccdc146 impaired spermiogenesis, mainly due to flagellum and manchette organization defects, finally led to MMAF-like phenotype. Furthermore, we demonstrated that CCDC146 could interact with both CCDC38 and CCDC42. It also interacts with intraflagellar transport (IFT) complexes IFT88 and IFT20. The knockout of this gene led to the decrease of ODF2, IFT88, and IFT20 protein levels, but did not affect CCDC38, CCDC42, or ODF1 expression. Additionally, we predicted and validated the detailed interactions between CCDC146 and CCDC38 or CCDC42, and built the interaction models at the atomic level. Our results suggest that the testis predominantly expressed gene Ccdc146 is essential for sperm flagellum biogenesis and male fertility, and its mutations might be associated with MMAF in some patients.2023Ma Y, Wu B, Chen Y, Ma S, Wang L, Han T, Lin X, Yang F, Liu C, Zhao J, Li W
38035773Lipocalin 2-A bone-derived anorexigenic and Œ≤-cell promoting signal: From mice to humans.The skeleton is traditionally known for its structural support, organ protection, movement, and maintenance of mineral homeostasis. Over the last 10‚Äâyears, bone has emerged as an endocrine organ with diverse physiological functions. The two key molecules in this context are fibroblast growth factor 23 (FGF23), secreted by osteocytes, and osteocalcin, a hormone produced by osteoblasts. FGF23 affects mineral homeostasis through its actions on the kidneys, and osteocalcin has beneficial effects in improving glucose homeostasis, muscle function, brain development, cognition, and male fertility. In addition, another osteoblast-derived hormone, lipocalin 2 (LCN2) has emerged into the researchers’ field of vision. In this review, we mainly focus on LCN2’s role in appetite regulation and glucose metabolism and also briefly introduce its effects in other pathophysiological conditions, such as nonalcoholic fatty liver disease, sarcopenic obesity, and cancer-induced cachexia.2024Yang Y, Liu J, Kousteni S
38030992Sperm chromatin structure assay (SCSASperm DNA integrity is increasingly seen as a critical characteristic determining reproductive success, both in natural reproduction and in assisted reproductive technologies (ART). Despite this awareness, sperm DNA and nuclear integrity tests are still not part of routine examinations for either infertile men or fertile men wishing to assess their reproductive capacity. This is not due to the unavailability of DNA and sperm nuclear integrity tests. On the contrary, several relevant but distinct tests are available and have been used in many clinical trials, which has led to conflicting results and confusion. The reasons for this are mainly the lack of standardization between different clinics and between the tests themselves. In addition, the small number of samples analyzed in these trials has often weakened the value of the analyses performed. In the present work, we used a large cohort of semen samples, covering a wide age range, which were simultaneously evaluated for sperm DNA fragmentation (SDF) using two of the most frequently used SDF assays, namely the TUNEL assay and the sperm chromatin structure assay (SCSA®). At the same time, as standard seminal parameters (sperm motility, sperm morphology, sperm count) were available for these samples, correlations between age, SDF and conventional seminal parameters were analyzed.2023Behdarvandian P, Nasr-Esfahani A, Tavalaee M, Pashaei K, Naderi N, Darmishonnejad Z, Hallak J, Aitken RJ, Gharagozloo P, Drevet JR, Nasr-Esfahani MH
38029492Gym lifestyle factors and male reproductive health: a study into young adult usage and perceptions.What level of awareness do young adults have regarding the potential impacts of gym lifestyle factors and supplementation on male infertility?2024Newman-Sanders A, Kirkman-Brown JC, Gallagher MT
38028760Semen proteomics reveals alterations in fertility-related proteins post-recovery from COVID-19.2023Dash A, Salkar A, Nissa MU, Makwana P, Athalye A, Parikh S, Srivastava S, Parikh F
38027181A short-term high-fat diet alters rat testicular activity and blood-testis barrier integrity through the SIRT1/NRF2/MAPKs signaling pathways.Overweight/obesity are metabolic disorder resulting from behavioral, environmental, and heritable causes. WHO estimates that 50% of adults and 30% of children and adolescents are overweight or obese, and, in parallel, an ongoing decline in sperm quality and male fertility has been described. Numerous studies demonstrated the intimate association between overweight/obesity and reproductive dysfunction due to a highly intricate network of causes not yet completely understood. This study expands the knowledge on the impact of a short-term high-fat diet (st-HFD) on rat testicular activity, specifically on steroidogenesis and spermatogenesis, focusing on the involved molecular mechanisms related to mitochondrial dynamics, blood-testis barrier (BTB) integrity, and SIRT1/NRF2/MAPKs pathways.2023Falvo S, Minucci S, Santillo A, Senese R, Chieffi Baccari G, Venditti M
38026720Evaluation of the Effect of Vitamin E on Reproductive Parameters in Morphine-Treated Male Mice.Morphine is a narcotic pain reliever that is prescribed to reduce postoperative pain and can produce reactive oxygen species (ROS). Therefore, it can have negative effects on spermatogenesis and male fertility. Vitamin E is an effective antioxidant which plays an important role in membrane lipid peroxidation due to increased ROS. The present study aimed to evaluate the effects of vitamin E and morphine on sperm parameters, level of malondialdehyde (MDA), and diameter of seminiferous tubules in morphine-treated mice.2023Arjmand K, Daneshi E, Pourmasumi S, Fathi F, Nasseri S, Sabeti P
38026028Proteomic differences in seminal fluid of social insects whose sperm differ in heat tolerance.In the coming years, climate change is likely to increase the frequency and intensity of heatwaves. In many organisms, heat stress provokes physiological perturbations and can lead to decreased male fertility. Bumblebees are endo-heterothermic but display interspecific differences in thermotolerance that could have conservation implications. For the species of concern2023Martinet B, Przybyla K, Decroo C, Wattiez R, Aron S
38024496Using a Decision Tree Algorithm Predictive Model for Sperm Count Assessment and Risk Factors in Health Screening Population.Approximately 20% of couples face infertility challenges and struggle to conceive naturally. Despite advances in artificial reproduction, its success hinges on sperm quality. Our previous study used five machine learning (ML) algorithms, random forest, stochastic gradient boosting, least absolute shrinkage and selection operator regression, ridge regression, and extreme gradient boosting, to model health data from 1375 Taiwanese males and identified ten risk factors affecting sperm count.2023Huang HH, Lu CJ, Jhou MJ, Liu TC, Yang CT, Hsieh SJ, Yang WJ, Chang HC, Chen MS
38023802The association between oral inflammatory load and semen and sperm functional analysis: A cross-sectional study.Studies have suggested a correlation between periodontitis and reduced male fertility. Inflammation has been described as the link between these ailments. Oral inflammatory load (OIL) can be measured through oral polymorphonuclear neutrophil (oPMN) count, which is associated with periodontal diseases. This cross-sectional study assessed the possible correlation between OIL and the functional parameters of sperm cells.2023Pourabbas R, Farajzadeh S, Babaloo A, Pazhohan A, Sadighi M, Hajebrahimi S, Pourabbas S, Tenenbaum HC
38021376Bisphenol-A disturbs hormonal levels and testis mitochondrial activity, reducing male fertility.How does bisphenol-A (BPA) influence male fertility, and which mechanisms are activated following BPA exposure?2023Ryu DY, Pang WK, Adegoke EO, Rahman MS, Park YJ, Pang MG
38020911A comparative analysis of fruit fly and human glutamate dehydrogenases inGlutamate dehydrogenases are enzymes that take part in both amino acid and energy metabolism. Their role is clear in many biological processes, from neuronal function to cancer development. The putative testis-specific2023Vedelek V, Vedelek B, Lőrincz P, Juhász G, Sinka R
38014244AXDND1 is required to balance spermatogonial commitment and for sperm tail formation in mice and humans.Dynein complexes are large, multi-unit assemblies involved in many biological processes including male fertility via their critical roles in protein transport and axoneme motility. Previously we identified a pathogenic variant in the dynein gene2023Houston BJ, Nguyen J, Merriner DJ, O’Connor AE, Lopes AM, Nagirnaja L, Friedrich C, Kliesch S, T√ºttelmann F, Aston KI, Conrad DF, Hobbs RM, Dunleavy JE, O’Bryan MK
38013430Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human.Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (2023Schneider S, Kovacevic A, Mayer M, Dicke AK, Arévalo L, Koser SA, Hansen JN, Young S, Brenker C, Kliesch S, Wachten D, Kirfel G, Strünker T, Tüttelmann F, Schorle H
38012911[Surgery to improve male fertility].At a time when increasing attention is being paid to the limitations and risks of in vitro fertilisation techniques, surgeries to improve male fertility are attracting growing interest.2023Huyghe E, Faix A, Methorst C
38012910[Medical treatments for male infertility].Treatments to stimulate spermatogenesis and antioxidant food supplements are often offered to infertile patients either before sperm extraction surgery to improve results, or as part of medically assisted reproduction or spontaneous fertility to increase the likelihood of a live birth.2023Methorst C, Faix A, Huyghe E
38012909[Infections and male infertility].The role of urogenital infections in male infertility has long been the subject of debate.2023Saint F, Huyghe E, Methorst C, Priam A, Seizilles de Mazancourt E, Bruyère F, Faix A
38012718Different mechanisms of X-ray irradiation-induced male and female sterility in Aedes aegypti.Aedes aegypti (Ae. aegypti) is the major vector that transmits many diseases including dengue, Zika, and filariasis in tropical and subtropical regions. Due to the growing resistance to chemical-based insecticides, biological control methods have become an emerging direction to control mosquito populations. The sterile insect technique (SIT) deploys high doses of ionizing radiation to sterilize male mosquitoes before the release. The Wolbachia-based population suppression method of the incompatible insect technique (IIT) involves the release of Wolbachia-infected males to sterilize uninfected field females. Due to the lack of perfect sex separation tools, a low percentage of female contamination is detected in the male population. To prevent the unintentional release of these Wolbachia-infected females which might result in population replacement, a low dose of X-ray irradiation is deployed to sterilize any female escapees. However, it remains unclear whether these irradiation-induced male and female sterilizations share common mechanisms.2023Zhang H, Trueman E, Hou X, Chew X, Deng L, Liew J, Chia T, Xi Z, Tan CH, Cai Y
38012716The construction of a testis transcriptional cell atlas from embryo to adult reveals various somatic cells and their molecular roles.The testis is a complex organ that undergoes extensive developmental changes from the embryonic stage to adulthood. The development of germ cells, which give rise to spermatozoa, is tightly regulated by the surrounding somatic cells.2023Salehi N, Totonchi M
38012524Clinical Utility of Sperm Function Tests in Predicting Male Fertility: A Systematic Review.Routine semen analysis provides considerable information regarding sperm parameters; however, it is not solely adequate to predict male fertility potential. In the past two decades, several advance sperm function tests have been developed. The present systematic review intends to assess the clinical utility of available advance sperm function tests in predicting the male fertility potential. A systematic literature search was conducted as per PRISMA guidelines using PubMed, MEDLINE, Google Scholar, and Cochrane Library. Different keywords either singly or in combination were used to retrieve the relevant articles related to sperm function tests, male fertility, and pregnancy outcomes. A total of 5169 articles were obtained, out of which 110 meeting the selection criteria were included in this review. The majorly investigated sperm function tests are hypo-osmotic swelling test, acrosome reaction test, sperm capacitation test, hemizona binding assay, sperm DNA fragmentation test, seminal reactive oxygen species test, mitochondrial dysfunction tests, antisperm antibody test, nuclear chromatin de-condensation (NCD) test, etc. The different advance sperm function tests analyse different aspects of sperm function. Hence, any one test may not be helpful to appropriately predict the male fertility potential. Currently, the unavailability of high-quality clinical data, robust thresholds, complex protocols, high cost, etc., are the limiting factors and prohibiting current sperm function tests to reach the clinics. Further multi-centric research efforts are required to fulfil the existing lacunas and pave the way for these tests to be introduced into the clinics.2024Sanyal D, Arya D, Nishi K, Balasinor N, Singh D
38009398A framework for identifying fertility gene targets for mammalian pest control.Fertility-targeted gene drives have been proposed as an ethical genetic approach for managing wild populations of vertebrate pests for public health and conservation benefit. This manuscript introduces a framework to identify and evaluate target gene suitability based on biological gene function, gene expression and results from mouse knockout models. This framework identified 16 genes essential for male fertility and 12 genes important for female fertility that may be feasible targets for mammalian gene drives and other non-drive genetic pest control technology. Further, a comparative genomics analysis demonstrates the conservation of the identified genes across several globally significant invasive mammals. In addition to providing important considerations for identifying candidate genes, our framework and the genes identified in this study may have utility in developing additional pest control tools such as wildlife contraceptives.2024Clark AC, Edison R, Esvelt K, Kamau S, Dutoit L, Champer J, Champer SE, Messer PW, Alexander A, Gemmell NJ
38008502The effect of various air pollution and participants’ age on semen quality in southern Taiwan.This study aimed to investigate the association between semen quality and air pollution in southern Taiwan.2023Lien HT, Tsai NC, Lin YJ, Lan KC
38006819Does SARS Cov-2 infection affect the IVF outcome – A systematic review and meta-analysis.What is the effect of SARS Cov-2 on IVF outcome?2024Kaur H, Chauhan A, Mascarenhas M
38002711Effects of COVID-19 Infection on Spermatogenesis, Oxidative Stress and Erectile Function.Our aim was to evaluate the effect of COVID-19 infection on male fertility and sexual function.2023Törzsök P, Oswald D, Steiner C, Abenhardt M, Ramesmayer C, Milinovic L, Plank B, Tischleritsch Z, Lusuardi L, Deininger S
38002013Sperm Mitochondrial Content and Mitochondrial DNA to Nuclear DNA Ratio Are Associated with Body Mass Index and Progressive Motility.Mitochondrial dysfunction is a risk factor in the pathogenesis of metabolic disorders. According to the energy requirements, oxidative phosphorylation and the electron transport chain work together to produce ATP in sufficient quantities in the mitochondria of eukaryotic cells. Abnormal mitochondrial activity causes fat accumulation and insulin resistance as cells require a balance between the production of ATP by oxidative phosphorylation (OXPHOS) in the mitochondria and the dissipation of the proton gradient to reduce damage from reactive oxygen species (ROS). This study aims to explore the relationship between the mitochondrial content of sperm and the ratio of mitochondrial DNA to nuclear DNA in relation to body mass index (BMI) and how it may affect the progressive motility of sperm cell. Understanding the relationships between these important variables will help us better understand the possible mechanisms that could connect sperm motility and quality to BMI, as well as further our understanding of male fertility and reproductive health.2023Moustakli E, Zikopoulos A, Skentou C, Bouba I, Tsirka G, Stavros S, Vrachnis D, Vrachnis N, Potiris A, Georgiou I, Zachariou A
37996913Association of diet and lifestyle factors with semen quality in male partners of Chinese couples preparing for pregnancy.Semen quality significantly influences conception, and its preservation is crucial for couples seeking pregnancy. We investigated dietary and lifestyle risk factors impacting semen quality.2023Mai H, Ke J, Zheng Z, Luo J, Li M, Qu Y, Jiang F, Cai S, Zuo L
37995749New strategies for germ cell cryopreservation: Cryoinjury modulation.Cryopreservation is an option for the preservation of pre- or post-pubertal female or male fertility. This technique not only is beneficial for human clinical applications, but also plays a crucial role in the breeding of livestock and endangered species. Unfortunately, frozen germ cells, including oocytes, sperm, embryos, and spermatogonial stem cells, are subject to cryoinjury. As a result, various cryoprotective agents and freezing techniques have been developed to mitigate this damage. Despite extensive research aimed at reducing apoptotic cell death during freezing, a low survival rate and impaired cell function are still observed after freeze-thawing. In recent decades, several cell death pathways other than apoptosis have been identified. However, the relationship between these pathways and cryoinjury is not yet fully understood, although necroptosis and autophagy appear to be linked to cryoinjury. Therefore, gaining a deeper understanding of the molecular mechanisms of cryoinjury could aid in the development of new strategies to enhance the effectiveness of the freezing of reproductive tissues. In this review, we focus on the pathways through which cryoinjury leads to cell death and propose novel approaches to enhance freezing efficacy based on signaling molecules.2023Jung SE, Ryu BY
37993789Dnali1 is required for sperm motility and male fertility in mice.The sperm flagellum is an evolutionarily conserved specialized organelle responsible for sperm motility and male fertility. Deleterious mutations in genes involved in the sperm flagellum assembly can often cause sperm motility defects and male infertility. The murine Dnali1 gene encodes a protein that is known to interact with the cytoplasmic dynein heavy chain 1.2023Zhou Y, Wang Y, Chen J, Wu B, Tang S, Zhang F, Liu C, Wang L
37992807Testicular ACE regulates sperm metabolism and fertilization through the transcription factor PPARγ.Testis angiotensin-converting enzyme (tACE) plays a critical role in male fertility, but the mechanism is unknown. By using ACE C-domain KO (CKO) mice which lack tACE activity, we found that ATP in CKO sperm was 9.4-fold lower than WT sperm. Similarly, an ACE inhibitor (ACEi) reduced ATP production in mouse sperm by 72%. Metabolic profiling showed that tACE inactivation severely affects oxidative metabolism with decreases in several Krebs cycle intermediates including citric acid, cis-aconitic acid, NAD, α-ketoglutaric acid, succinate, and L-malic acid. We found that sperms lacking tACE activity displayed lower levels of oxidative enzymes (CISY, ODO1, MDHM, QCR2, SDHA, FUMH, CPT2, and ATPA) leading to a decreased mitochondrial respiration rate. The reduced energy production in CKO sperms leads to defects in their physiological functions including motility, acrosine activity, and fertilization in vitro and in vivo. Male mice treated with ACEi show severe impairment in reproductive capacity when mated with female mice. In contrast, an angiotensin II receptor blocker (ARB) had no effect. CKO sperms express significantly less peroxisome proliferators-activated receptor gamma (PPARγ) transcription factor, and its blockade eliminates the functional differences between CKO and WT sperms, indicating PPARγ might mediate the effects of tACE on sperm metabolism. Finally, in a cohort of human volunteers, in vitro treatment with the ramipril or a PPARγ inhibitor reduced ATP production in human sperm and hence its motility and acrosine activity. These findings may have clinical significance since millions of people take ACEi daily, including men who are reproductively active.2024Shibata T, Bhat SA, Cao D, Saito S, Bernstein EA, Nishi E, Medenilla JD, Wang ET, Chan JL, Pisarska MD, Tourtellotte WG, Giani JF, Bernstein KE, Khan Z
37992210FAM71D is dispensable for spermatogenesis and male fertility in mice.In mammals, the generation of sperm cells capable of fertilization is a highly complex process including spermatogenesis in the testis and maturation in the epididymis. In our previous study, we have demonstrated that FAM71D (Family with sequence similarity 71, member D), which could interact with calmodulin, was highly expressed in human and mouse testis. To investigate the physiological role of FAM71D in spermatogenesis, we next generate Fam71d loss-of-function mouse model using CRISPR/Cas9 technology. We performed immunofluorescence and RT-qPCR to examine the protein and mRNA expression in testicular cells. We found that FAM71D was predominantly localized in the round and elongated spermatids. And FAM71D KO mice displayed normal development of germ cell and fertility. Furthermore, testicular histology and sperm concentration showed no significant difference between WT and KO mice. These data demonstrate that FAM71D is dispensable for mouse spermatogenesis and male fertility.2023Mo S, Deng K, Cao C, Gui Y, Ma Q
37985585Bisphenol A exposure decreases sperm production and male fertility through inhibition PCBP2 expression.Growing evidence suggests that the exposure of bisphenol A (BPA), an endocrine disruptor that commonly present in the environment, can impair reproduction. However, conflicting results have been reported, and the underlying mechanism has not been fully understood. In this study, 3-week-old male mice were oral exposed to 50 mg/kg/d BPA or equivalent corn oil for 28 days. Their testis and epididymis were then collected for morphology examination by HE stains. The number of sperm was counted, and the morphology was analyzed by PNA (peptide nucleic acid) and pap staining. Fertilization capacity and successful rate were analyzed after mating with wide-type females. Spermatid DNA damage and apoptosis were evaluated by DFI, γH2AX stain, and TUNEL assay. RNA sequencing analysis was conducted to identify differentially expressed genes in testicular tissue of mice exposed to BPA. RNA interference was used to verify the regulatory mechanism of BPA exposure on gene expression in GC-2 cells. Our data showed that the total number of sperm was decreased and the morphology was impaired in BPA-exposed mice. In addition, the serum testosterone level and fertilization efficiency were also reduced. Mechanism studies showed that BPA could suppress the expression of PCBP2, a key regulatory gene in spermatid development, by activating the EZH2/H3K27me3. In conclusion, we found that BPA exposure can impair spermatid development via affecting key gene expression that is at least partially due to epigenetic modification.2023Cao Y, Xu J, Liu J, Liang Y, Ao F, Wang S, Wei Z, Wang L
37984745Low-Fat, High-Carbohydrate Diets Reduce Body Weight and Sperm Count but Increase Sperm Motility in Mice.Male reproduction is impacted by both over- and under-nutrition, demonstrated by animal studies using high-fat and low-protein dietary interventions. Little is known about the impacts of low-fat, high-carb diets and types of dietary carbohydrates on sperm traits.2024Crean AJ, Pulpitel TJ, Pini T, Rickard JP, de Graaf SP, Senior AM, Simpson SJ, Wali JA
37981113Asperosaponin VI protects against spermatogenic dysfunction in mice by regulating testicular cell proliferation and sex hormone disruption.Studies have found that the causes of male infertility are complex, and spermatogenic dysfunction accounts for 30%-65% of male infertility causes, which is the main cause of male infertility. Asperosaponin VI (ASVI) is a saponin extracted from the traditional Chinese herb Dipsacus asperoides C.Y.Cheng & T.M.Ai. However, the precise protective impact and underlying mechanism of ASVI in the therapy of spermatogenic dysfunction remain unknown.2024Cui YH, Ma L, Hai DM, Chi YN, Dong WJ, Lan XB, Wei W, Tian MM, Peng XD, Yu JQ, Liu N
37979495Regulatory mechanisms of SoxD transcription factors and their influences on male fertility.Members of the SRY-related box (SOX) subfamily D (SoxD) of transcription factors are well conserved among vertebrate species and play important roles in different stages of male reproductive development. In mammals, the SoxD subfamily contains three members: SOX5, SOX6 and SOX13. Here, we describe their implications in testicular development and spermatogenesis, contributing to fertility. We also cover the mechanisms of action of SoxD transcription factors in gene regulation throughout male development. The specificity of activation of target genes by SoxD members depends, in part, on their post-translational modifications and interactions with other partners. Sperm production in adult males requires the coordination in the regulation of gene expression by different members of the SoxD subfamily of transcription factors in the testis. Specifically, the regulation of genes promoting adequate spermatogenesis by SoxD members is discussed in comparison between species.2023Diawara M, Martin LJ
37977364Evaluation of precopulatory pairing behaviour and male fertility in a marine amphipod exposed to plastic additives.Plastics contain a mixture of chemical additives that can leach into the environment and potentially cause harmful effects on reproduction and the endocrine system. Two of these chemicals, N-butyl benzenesulfonamide (NBBS) and triphenyl phosphate (TPHP), are among the top 30 organic chemicals detected in surface and groundwater and are currently placed on international watchlist for evaluation. Although bans have been placed on legacy pollutants such as diethylhexyl phthalate (DEHP) and dibutyl phthalate (DBP), their persistence remains a concern. This study aimed to examine the impact of plastic additives, including NBBS, TPHP, DBP, and DEHP, on the reproductive behaviour and male fertility of the marine amphipod Echinogammarus marinus. Twenty precopulatory pairs of E. marinus were exposed to varying concentrations of the four test chemicals to assess their pairing behaviour. A high-throughput methodology was developed and optimised to record the contact time and re-pair time within 15 min and additional point observations for 96 h. The study found that low levels of NBBS, TPHP, and DEHP prolonged the contact and re-pairing time of amphipods and the proportion of pairs reduced drastically with re-pairing success ranging from 75% to 100% in the control group and 0%-85% in the exposed groups at 96 h. Sperm count declined by 40% and 60% in the 50 μg/l and 500 μg/l DBP groups, respectively, whereas TPHP resulted in significantly lower sperms in 50 μg/l exposed group. Animals exposed to NBBS and DEHP showed high interindividual variability in all exposed groups. Overall, this study provides evidence that plastic additives can disrupt the reproductive mechanisms and sperm counts of amphipods at environmentally relevant concentrations. Our research also demonstrated the usefulness of the precopulatory pairing mechanism as a sensitive endpoint in ecotoxicity assessments to proactively mitigate population-level effects in the aquatic environment.2024Green-Ojo B, Botelho MT, Umbuzeiro GA, Gomes V, Parker MO, Grinsted L, Ford AT
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