Male Infertility Research Articles

Association of Kisspeptin and KISS1 Gene Polymorphism (rs35431622) with Circulating Sex Hormones and Male Infertility.

This research delves into the association of Kisspeptin and the KISS1 gene (rs35431622) single nucleotide polymorphism with circulating sex hormones and semen parameters in males diagnosed with infertility. Eighty male participants were recruited from fertility clinic, were divided into two groups: Group A, characterized by normal sperm count and Group B, exhibiting low count. The analysis involved assessing hormone levels Kisspeptin, follicle stimulating hormone, luteinizing hormone, total testosterone and sex hormone binding globulin by utilizing ELISA, investigating the association of the KISS1 gene SNP with these variables through Tetra amplification refractory mutation system-PCR and Gel Electrophoresis. The findings revealed that males a low sperm count displayed notably reduced levels of Kisspeptin and free testosterone, accompanied by increased luteinizing hormone and follicle stimulating hormone. The KISS1 gene SNP rs35431622 (Q36R) demonstrated a 53.3% frequency of the heterozygous mutant TA genotype and OR 0.19 (CI 0.05-0.71) among infertile males, indicating its potential implications a risk factor for male infertility. This study emphasizes the significance of Kisspeptin in overseeing male reproductive health and highlights its potential as a marker for hormonal dysregulation in male infertility.

Mechanisms of oxidative stress-induced sperm dysfunction

Oxidative stress plays a pivotal role in male infertility by impairing sperm function through various molecular mechanisms. This review explores the impact of excessive reactive oxygen species (ROS) on spermatozoa, particularly focusing on lipid peroxidation, DNA fragmentation, and protein oxidation. Lipid peroxidation damages sperm membranes, reducing fluidity and motility. ROS-induced DNA fragmentation compromises genetic integrity, potentially leading to infertility and adverse offspring outcomes. Protein oxidation alters key structural proteins, impairing sperm motility and the ability to fertilize an egg. The primary sources of oxidative stress in sperm include leukocyte activity, mitochondrial dysfunction, and environmental factors such as smoking and pollution. Despite the presence of natural antioxidant defenses, spermatozoa are particularly vulnerable due to limited repair mechanisms. The review highlights the importance of early intervention through antioxidant therapies and lifestyle changes to mitigate the detrimental effects of oxidative stress on male fertility. Further research is essential to enhance therapeutic approaches and improve reproductive outcomes.

Evaluation of Risk Factors and a Gene Panel as a Tool for Unexplained Infertility Diagnosis by Next-Generation Sequencing

Background and Objective: Unexplained infertility is a major challenge in reproductive medicine and requires advanced diagnostic approaches to identify the underlying factors accurately. This study aims to evaluate the utility of risk factor analysis and a gene panel in diagnosing unexplained infertility using the next-generation sequencing (NGS) technology. Our study aimed to characterize and identify risk and genetic factors associated with unexplained infertility. Materials and methods: A cohort of patients with unexplained infertility was comprehensively screened for risk factors and genetic variations using a targeted gene panel (10 couples with unexplained infertility (UI) and 36 fertile couples). 108 articles were selected (58 on female infertility and 50 on male infertility) presenting genes that may be associated with unexplained infertility. A gene panel for unexplained infertility was compiled based on the literature data. A customized virtual panel was created from the exome sequencing data. Results: In the female group, controls had a higher mean age, while in the male patients, both groups were similar in terms of age. Both gender groups had comparable BMI values. No significant associations (p > 0.05) between risk factors and unexplained infertility were found when evaluating anthropometric parameters and other sociodemographic characteristics. In two male patients (20%), a molecular defect was detected in NGS variants classified aspossible benign and probably benign In particular, missense variants were identified in the UGT2B7 and CATSPER2 genes, A molecular defect classified as probably damaging was found in five female patients (50%). In particular, missense variants were identified in the CAPN10, MLH3, HABP2, IRS1, GDF9, and SLC19A1 genes. Conclusions: The study emphasizes that unexplained infertility is often related to mechanisms beyond causative mutations and highlights the need for integrative genomic research involving broader gene panels and multi-faceted approaches, including transcriptomics and epigenetics, to uncover latent genetic predispositions.

Fertility in male patients with familial Mediterranean fever and paternal effect of FMF on pregnancy outcomes and complications.

This study investigates the impact of Familial Mediterranean Fever (FMF) and its treatment on male infertility, and the paternal effect of FMF on pregnancy outcomes or complications. We enrolled 282 adult male FMF patients and excluded 102 for never attempting pregnancy. Demographic and clinical data, including MEFV mutation status and treatment history, were collected. Fertility status and pregnancy outcomes were assessed through interviews and medical records. Statistical analysis was performed using Fisher's exact test, with significance set at p < 0.05. Among the 180 patients who attempted pregnancy, 177 (98.3%) achieved pregnancy. Only 3 (1.7%) were infertile. A total of 452 pregnancies were conceived, with 85.0% resulting in live births. Miscarriages occurred in 11.9%, stillbirths in 0.9%, and ectopic pregnancies in 0.9%. The most common complication was preterm birth (4.2%), followed by gestational diabetes (2.1%). Eleven patients with amyloidosis achieved 39 pregnancies, with no cases of infertility. FMF does not lead to decreased male fertility or adverse pregnancy outcomes. Colchicine is safe for use during conception. Male FMF patients and their partners do not need additional precautions during pregnancy attempts and follow-up.

Establishing the Mechanisms Involved in the Environmental Exposure to Polychlorinated Biphenyls (PCBs) in the Risk of Male Infertility.

Exposure to toxic chemicals, such as plasticizers, alkylphenol compounds, and polychlorinated biphenyls (PCBs), has increased due to environmental contamination. PCBs, categorized as persistent organic pollutants (POPs), are lipophilic chemicals commonly used in lubricants, cutting oils, and electrical insulators. PCBs may have detrimental effects on hormone-producing glands, potentially contributing to male infertility. Thus, the objective of this study was to provide a comprehensive overview of the adverse effects of PCBs on the male reproductive system. Searches of three electronic databases were performed using MESH terms and 32 studies were included. Although the exact mechanism of action for PCBs remains unclear, several PCBs are regarded as potential endocrine disruptors due to their ability to interact with hormone signaling pathways. PCBs have been found to disrupt physiological functions by mimicking endogenous hormones as agonists or antagonists, altering patterns of hormone synthesis, hormone receptor affinities or numbers, and modulating enzymes involved in hormone secretion. These reports highlight the pleiotropic nature of PCB function and the susceptibility of the reproductive system. Endocrine-disrupting PCBs can mimic, alter, or block hormonal responses, inhibiting natural signaling to the testes and epididymis via various mechanisms such as binding to sex hormone-binding globulin and androgen-binding protein or blocking cell surface receptors. Furthermore, PCBs can alter the hormonal environment in the prostate or seminal vesicles by changing the affinity of androgens for their receptors. The testicles and genital organs may be susceptible to various estrogenic effects, leading to changes in the quality or quantity of their secretions and the volume of semen.

LRRC56 deletion causes primary ciliary dyskinesia in mice characterized by dynein arms defects.

Leucine Rich Repeat Containing protein 56 (LRRC56), also known as DNAAF12, is a member of the LRRC superfamily, whose dysfunction is associated with mucociliary clearance and laterality defects in humans. Here, we generated LRRC56-knockout mice using the CRISPR/Cas9 nuclease system to specifically target exons 4-5 of the LRRC56 gene. We observed that homozygous LRRC56 gene deletion is definitely deleterious, as 27.8% of LRRC56-/- mice died before adulthood. Among the surviving LRRC56-/- mice, the most prominent phenotypes included hydrocephalus, situs inversus, male infertility, and bronchiectasis. Transmission electron microscopy revealed defects in dynein arms of cilia and disorganized axonemal structure in flagella. Immunofluorescence analysis similarly revealed the absence of inner and outer dynein arm markers DNALI1 and DNAI2 in the cilia. Heterozygous LRRC56+/- mice developed normally, without exhibiting any symptoms of primary ciliary dyskinesia. In conclusion, the knockout of the LRRC56 gene in mice leads to a range of conditions consistent with primary ciliary dyskinesia. The absence of DNALI1 and DNAI2 signaling in knockout mouse cilia supports the critical role of the LRRC56 gene in dynein arm assembly.

CD56-Positive NK Cells and CD138-Positive Plasma Cells in Basal Decidua of Term Placentas in Singleton Pregnancies After Assisted Reproductive Technology Treatment of Endometriosis-Related Infertility

A eutopic endometrium in endometriosis shows altered immune responses, including abnormalities of NK cells and expression of plasma cells, related to reproductive issues. This study investigated the counts of CD56-positive NK cells and CD138-positive plasma cells in the basal decidua of term placentas in singleton pregnancies after endometriosis-related infertility conceived by assisted reproductive technology (ART). This single-center, case-control study involved immunohistochemical analysis of CD56-positive NK cells and CD138-positive plasma cells in basal decidua using primary monoclonal mouse antibodies, followed by secondary antibodies using a standardized protocol. CD56 and CD138 immunohistochemically positive cells were reported as the total cell count for each studied antibody expressed per 1 mm2 of basal decidua (Olympus BX46 and Olympus Image Analyzer). Placental samples containing basal decidua from 36 participants with endometriosis-related infertility who conceived by ART, 31 participants with male factor infertility who conceived by ART and 40 healthy controls were included. Endometriosis decidua showed the lowest median count of CD56-positive NK cells (11.5 / mm2, p = 0.039) in BD compared to male factor group (25 / mm2) and healthy controls (24.5 / mm2). No differences were found for CD138-positive plasma cells counts between study groups. Basal decidua in pregnancies after endometriosis-related infertility showed reduced total count of CD56-positive NK cells, without differences in the CD138-positive plasma cell counts compared to control groups. Future studies should investigate how changes in NK cells throughout pregnancy affect the development of perinatal complications and placental pathologies in women with endometriosis, which could uncover potential diagnostic and therapeutic targets.

Chronic asymptomatic orchitis in dogs alters Sertoli cell number and maturation status

Infertility due to non-obstructive azoospermia is a common diagnosis in infertile male dogs. Chronic asymptomatic orchitis (CAO) has been postulated as a significant cause of non-obstructive azoospermia in acquired male canine infertility. Despite severe microenvironmental changes, some resilient spermatogonial stem cells persist in CAO-affected testes. As Sertoli cells play an essential role in spermatogenesis and the testicular micromilieu, they represent a new target for CAO potential treatment and consequently deserve further investigation. To investigate Sertoli cell number and maturational status, different markers [Vimentin, anti-Müllerian hormone (AMH), and cytokeratin-18 (CK18)] were evaluated in healthy and CAO-affected testes at mRNA and protein levels. Sertoli cell number was reduced in CAO-affected dogs. Sertoli cells also partly returned to an immature status, as indicated by the expression of AMH and CK18 at mRNA and protein levels. The degree of spermatogenesis disruption matched with the degree of Sertoli cell alterations. The investigation of CAO in this study is limited by the number of samples and the lack of testicular volume measurements, but this does not diminish its importance in new findings. In conclusion, this study identifies alterations in Sertoli cell number and maturation status as a cause or consequence of CAO. The results indicate the need to restore Sertoli cell function as a potential therapeutic target for a successful restart of spermatogenesis.

Sonographic Diagnosis of Anterior Nutcracker Phenomenon and its Prevalence in Nigerian Males with Varicoceles

Abstract Background: The nutcracker phenomenon (NCP) is a rare and often unrecognised cause of varicocele, haematuria, and chronic pelvic pain due to the left renal vein (LRV) compression between the aorta and the superior mesenteric artery (anterior nutcracker). Its varied clinical manifestations make the diagnosis difficult and usually delayed. A high index of clinical suspicion, with appropriate imaging studies is crucial for the diagnosis. Objectives: We used a colour Doppler ultrasound scan to investigate the anatomic and haemodynamic properties of testicular and renal venous drainage. The emphasis was to determine the presence or absence of NCP, its possible effects on varicocele formation and severity, and its relationship with the body mass index (BMI) of the subjects. Materials and Methods: We carried out Doppler scrotal and upper abdominal ultrasound examinations of 100 subjects with male infertility and clinical varicoceles (group A), and 100 controls with male infertility but without varicoceles (group B). The mean peak velocity (PV) and the anteroposterior (AP) diameters of different segments of the renal veins, as well as the diameters of the testicular veins of the subjects in the two groups were measured and compared. The ratios of the PV and the diameters between the hilar portion and the aorto-mesenteric portion of the LRV were also calculated and compared. A PV ratio or anteroposterior diameter ratio between the two portions greater or equal to 5.0 was considered diagnostic of NCP. The diagnosis of varicocele was confirmed by visualising a dilated pampiniform plexus vein measuring greater than 2 mm in diameter using an ultrasound scan. Results: Six out of 100 subjects in group A had diameter and PV ratios (≥5.0) in the LRV that suggested the presence of NCP, and all participants in group B had neither diameter nor PV ratio suggestive of NCP. The prevalence of NCP seen within the varicocele group in this study was statistically significant (P = 0.038). Five (83.3%) of the six subjects in the NCP-associated varicocele subgroup had microscopic haematuria, orthostatic proteinuria, or both; these qualified them for the diagnosis of nutcracker syndrome (NCS), A significantly lower mean BMI (P = 0.004) was noted among the NCP-associated varicocele subgroup compared to those without NCP. Conclusion: Our findings indicate that the NCP is a significant finding in patients with varicoceles in our environment, and it is more common with lower BMI.

Human chorionic gonadotropin-based clinical treatments for infertile men with non-obstructive azoospermia.

Spermatogenesis is primarily controlled by follicle-stimulating hormone and luteinizing hormone-driven testosterone. Luteinizing hormone acts on the Leydig cells, stimulating steroid production, predominantly testosterone, and activating critical inter-related spermatogenesis regulatory pathways. Despite evidence that exogenous gonadotropins containing luteinizing hormone activity, particularly human chorionic gonadotropin, can effectively restore spermatogenesis in azoospermic males with hypogonadotropic hypogonadism, the use of these drugs to treat other forms of non-obstructive azoospermia is the subject of an ongoing debate. In this review, we delve into the molecular properties and functions of human chorionic gonadotropin in spermatogenesis regulation and explore available preparations for therapeutic use. We examine the evidence regarding the effectiveness of human chorionic gonadotropin in treating infertility in men with pre-testicular or testicular non-obstructive azoospermia and, additionally, identify the main areas for future research. Our review highlights the critical role of luteinizing hormone activity in spermatogenesis and emphasizes the potential of human chorionic gonadotropin in treating male infertility. The variation in the characteristics of patients with non-obstructive azoospermia underscores the importance of assessing hormonal profiles when contemplating hormonal treatment for these patients. A novel stratification of male infertility patients, the APHRODITE criteria, which considers clinical and laboratory indicators, may assist in identifying individuals who could benefit from human chorionic gonadotropin therapy. While accumulating evidence suggests promising venues for pharmacological treatment in male infertility, including non-obstructive azoospermia, further research is required to completely elucidate the mechanisms underlying the effects of exogenous gonadotropins with luteinizing hormone activity on sperm production and to establish the most effective dosages and treatment durations.

Redox signaling regulation in human spermatozoa: a primary role of peroxiredoxins.

Reactive oxygen species (ROS) play a dual role in mammalian spermatozoa. At high levels, they are detrimental to sperm function since they can promote oxidative stress that produces oxidation of protein, lipids, and sperm DNA. This oxidative damage is associated with male infertility. On the other hand, when ROS are produced at low levels, they participate in the redox signaling necessary for sperm capacitation. Capacitation-associated ROS are produced by the sperm oxidase, whose identity is still elusive, located in the plasma membrane of the spermatozoon. ROS, such as superoxide anion, hydrogen peroxide, nitric oxide, and peroxynitrite, activate protein kinases and inactivate protein phosphatases with the net increase of specific phosphorylation events. Peroxiredoxins (PRDXs), antioxidant enzymes that fight against oxidative stress, regulate redox signaling during capacitation. Among them, PRDX6, which possesses peroxidase and calcium-independent phospholipase A2 (iPLA2) activities, is the primary regulator of redox signaling and the antioxidant response in human spermatozoa. The lysophosphatidic acid signaling is essential to maintain sperm viability by activating the phosphatidylinositol 3-kinase/protein kinase (PI3K/AKT) pathway, and it is regulated by PRDX6 iPLA2, protein kinase C (PKC), and receptor-type protein tyrosine kinase. The understanding of redox signaling is crucial to pave the way for novel diagnostic tools and treatments of male infertility.

Deletion of an evolutionarily conserved TAD boundary impacts spermatogenesis in mice

Abstract Spermatogenesis is a complex process that can be disrupted by genetic and epigenetic changes, potentially leading to male infertility. Recent research has rapidly increased the number of protein coding mutations causally linked to impaired spermatogenesis in humans and mice. However, the role of non-coding mutations remains largely unexplored. As a case study to evaluate the effects of non-coding mutations on spermatogenesis, we first identified an evolutionarily conserved topologically associated domain (TAD) boundary near two genes with important roles in mammalian testis function: Dmrtb1 and Lrp8. We then used CRISPR-Cas9 to generate a mouse line where 26 kb of the boundary was removed including a strong and evolutionarily conserved CTCF binding site. ChIP-seq and Hi-C experiments confirmed the removal of the CTCF site and a resulting mild increase in the DNA–DNA interactions across the domain boundary. Mutant mice displayed significant changes in testis gene expression, higher frequency of histological abnormalities, a drop of 47–52% in efficiency of meiosis, a 15–18% reduction in efficiency of spermatogenesis, and consistently, a 12–28% decrease in daily sperm production compared to littermate controls. Despite these quantitative changes in testis function, mutant mice show no significant changes in fertility. This suggests that non-coding deletions affecting testis gene regulation may have smaller effects on fertility compared to coding mutations of the same genes. Our results demonstrate that disruption of a TAD boundary can have a negative impact on sperm production and highlight the importance of considering non-coding mutations in the analysis of patients with male infertility.

Physical activity and male reproductive function.

Fecundity is declining in humans, which is partly due to male infertility. Poor sperm parameters, the main contributors to male infertility, are associated with sedentary, unhealthy lifestyle and poor dietary habits. Long periods of sedentary work lead to visceral adiposity and persistently elevated scrotal temperatures, which adversely affect spermatogenesis. Apart from increasing scrotal temperatures, excessive visceral adiposity exacerbates adipocyte dysfunction with increased pro-inflammatory adipokine release, like leptin. These, together with the increased scrotal temperature, are responsible for the poor sperm quality. The importance of regular physical activity in male fertility remains a matter of debate, as not all forms of exercises have been found to benefit sperm function. Sperm parameters are, nevertheless, somewhat better in active than in sedentary men. It now appears that low-to-moderate intensity exercises are more beneficial for male reproductive health than high-intensity exercises, which have a negative effect on spermatozoa. Low-to-moderate intensity exercises, in general, improve the overall organ-system function in the body, improve the management of body weight and oxidative stress, consequently improving sperm parameters. The detrimental effects of high-intensity exercises on spermatozoa result from disruption in the hypothalamus-pituitary-gonadal-axis, raised testicular temperature and increased oxidative stress. It, therefore, seems that not all types of exercises are beneficial for male reproductive health. Although some low-to-moderate intensity exercises improve male reproductive function, there remains a need to identify the best form of low-to-moderate intensity exercises, particularly those that do not increase testicular temperature or oxidative stress, to help maintain normal body weight and male reproductive health.

The association between consumption of ultra-processed foods and sperm quality parameters: a cross-sectional study

BackgroundWhile recent studies suggest a correlation between unhealthy dietary patterns, oxidative stress, inflammation, and male infertility, the potential association between ultra-processed foods (UPFs) and male infertility remains underexplored. Therefore, the aim of the present study was to investigate the association between UPF intake and male infertility by evaluating sperm quality parameters.MethodsThe participants (n = 260) of the current cross-sectional study were recruited from an infertility center in Isfahan Province, Iran. Four semen parameters—such as total sperm motility, sperm concentration, sperm volume, and normal sperm morphology—were evaluated. Also, the participants’ food intake was assessed using a validated 168-item food frequency questionnaire. Moreover, the NOVA system was employed to calculate the UPF index. The association between UPFs and sperm parameters was analyzed using logistic regression.ResultsIn the crude model, no significant associations were observed between the second and last tertiles of UPFs with abnormalities in sperm concentration, total motility, and morphology (p > 0.05 for all). However, after adjusting for age, marriage duration, body mass index, physical activity, depression, anxiety, stress, energy intake, cigarette history, and mineral and vitamin supplements, a significantly higher association was identified between the second tertile of UPFs and abnormalities in sperm concentration (odds ratio (OR) = 3.962, 95% confidence interval (CI): 1.345–11.670, p = 0.013).ConclusionsIn conclusion, although the analysis did not find significant associations between UPF consumption and impaired sperm motility and morphology, it revealed significant trends linking higher UPF intake with lower sperm concentration. If future studies confirm these results, they could aid in designing interventional and preventive programs aimed at addressing infertility in men of reproductive age in the field of public health.

Unveiling the Emerging Role of Klotho: A Comprehensive Narrative Review of an Anti-aging Factor in Human Fertility.

Klotho, an anti-aging protein, plays a vital role in diverse biological functions, such as regulating calcium and vitamin D levels, preventing chronic fibrosis, acting as an antioxidant and anti-inflammatory agent, safeguarding against cardiovascular and neurodegenerative conditions, as well as exerting anti-apoptotic, anti-senescence effects. Additionally, it contributes to metabolic processes associated with diabetes and exhibits anti-cancer properties. This protein is commonly expressed in organs, such as kidneys, brain, pancreas, parathyroid glands, ovaries, and testes. Recent research has highlighted its significance in human fertility. This narrative review provides insight into the involvement of Klotho protein in male and female fertility, as well as its potential role in managing human infertility in the future. In this study, a search was conducted on literature spanning from November 1997 to June 2024 across multiple databases, including PUBMED, SCOPUS, and Google Scholar, focusing on Klotho proteins. The search utilized keywords, such as "discovery of Klotho proteins," "Biological functions of Klotho," "Klotho in female fertility," "Klotho and PCOS," "Klotho and cryopreservation," and "Klotho in male infertility." Inclusion criteria comprised full-length original or review articles, as well as abstracts, discussing the role of Klotho protein in human fertility, published in English in various peer-reviewed journals. Exclusion criteria involved articles published in languages other than English. Hence, due to its anti-aging characteristics, Klotho protein presents potential roles in male and female fertility and holds promising prospects for reproductive medicine. Further, it holds the potential to become a valuable asset in addressing infertility concerns for both males and females.

The role of seminal oxidation reduction potential in male infertility. A systematic review and meta-analysis

The role of seminal oxidation reduction potential in male infertility. A systematic review and meta-analysis

ASB1 engages with ELOB to facilitate SQOR ubiquitination and H2S homeostasis during spermiogenesis.

Male infertility, frequently driven by oxidative stress, impacts half of infertile couples globally. Despite its significance, the precise mechanisms governing this process remain elusive. In this study, we demonstrate that ASB1, the substrate recognition subunit of a ubiquitin ligase, is highly expressed in the mouse testis. Mice lacking the Asb1 gene exhibit severe fertility impairment, characterized by oligoasthenoteratozoospermia. Subsequent investigations unveiled that Asb1 knockout (Asb1-KO) mice encountered excessive oxidative stress and decreased hydrogen sulfide (H2S) levels in their testes, and severe sperm DNA damage. Notably, the compromised fertility and sperm quality in Asb1-KO mice was significantly ameliorated by administering NaHS, a H2S donor. Mechanistically, ASB1 interacts with ELOB to induce the instability of sulfide-quinone oxidoreductase (SQOR) by enhancing its K48-linked ubiquitination on residues K207 and K344, consequently triggering proteasomal degradation. This process is crucial for preserving H2S homeostasis and redox balance. Overall, our findings offer valuable insights into the role of ASB1 during spermiogenesis and propose H2S supplementation as a promising therapeutic approach for oxidative stress-related male infertility.

Drosophila AK-3, a homologue of human CKMT1B, is essential for spermiogenesis.

Spermatogenesis is a conserved process across animals, involving in proliferation and maintenance of germ stem cells, haploid spermatid production via meiosis, generation of mature sperm with unique shapes. Our previous studies revealed that after ocnus (ocn) knockdown in germlines, the male flies Drosophila melanogaster were sterile, and the expression levels of many proteins were significantly changed. Among these proteins, CG4546 (arginine kinase 3, AK-3) displayed drastically downregulated, implying its crucial role in fly spermatogenesis. Here, we demonstrate that AK-3 was highly expressed in Drosophila testes. Knockdown of the AK-3 in testes leads to scattered nuclear bundles, loss of the central paired microtubule in the flagellar axoneme, disrupted individualization complexes (ICs), lack of mature sperm in seminal vesicles, and thus resulting in male complete infertility. Notably, Drosophila AK-3 shares homology with human CKMT1B. Expression of human CKMT1B can rescue the defects in late spermatogenesis and male sterility caused by AK-3 knockdown in flies, indicating that this gene is evolutionarily and functionally conserved. These results suggest that AK-3 contributes to the regulation of spermiogenesis, especially the assembly and stabilizing of the axonemal microtubules during the sperm elongation. These data substantiate the importance of arginine kinase during spermatogenesis and its evolutionary conservation, and might provide fundamental information for studying the function of CKMT1B in male fertility in humans.

Cryopreserved sperm among patients with Oligoasthenoteratozoospermia.

This study investigates sperm utilization and disposal patterns in Oligoasthenoteratozoospermia (OAT) patients undergoing long-term sperm storage. OAT is a major contributor to male infertility. Cryopreservation is a common practice as a "fertility insurance" in case of further deterioration until azoospermia. However, long-term storage practices and utilization rates remain unclear. In this retrospective study spanning from October 1993 to December 2021, we examined men diagnosed with OAT who underwent spermatozoa cryopreservation. Data from medical records included utilization and disposal of sperm samples, age and paternity status at initial cryopreservation. We analyzed the data over 10years using Kaplan-Meier curves, compared age and paternity status with the log-rank test. Among 238 patients undergoing semen cryopreservation due to the indication of OAT, 45 utilized sperm for fertility treatments, with a third using all frozen straws and others using only a portion. Sixteen patients used sperm due to azoospermia. Additionally, 54 requested the disposal of all cryopreserved straws. A Kaplan-Meier analysis revealed that after 10years, 25.9% of men used cryopreserved sperm, while 31.2% opted for disposal. Most participants did not use or dispose of preserved sperm. After 10years, no significant differences were observed in usage or disposal based on age or paternity status. Our analysis of sperm utilization in OAT patients undergoing cryopreservation revealed a key finding: nearly half exhibited a "wait-and-see" approach. Unlike other indication for sperm preservation, age and paternity did not significantly influence utilization or disposal decisions. This suggests unique factors drive decision-making in OAT patients, highlighting the need for tailored cryopreservation management strategies.

IGF2BP1 stabilizes Akt2 mRNA to promote glucose metabolism and maintain spermatogonial proliferation.

Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1), as a newly identified N6-methyladenosine (m6A) methylation reader, plays a key role in mRNA stability, alternative splicing, and translation. However, the function of IGF2BP1 and its target genes in the development of male germ cells remains unclear. In the present study, Western blotting, immunofluorescence, and other cellular methods were used to confirm whether IGF2BP1 is expressed throughout the male germline with high abundance in spermatogonia of mice, and whether its downregulation inhibits spermatogonia proliferation in vitro. Through RNA sequencing, dual luciferase reporter assays, RIP-qPCR, and mRNA stability experiments, it was identified that Akt2 is one of the target genes of IGF2BP1. By stabilizing Akt2 mRNA in an m6A-dependent manner, IGF2BP1 maintains spermatogonial proliferation. Furthermore, co-immunoprecipitation and mass spectrometry analyses revealed that PABPC1, DDX5, and FXR1 interact with IGF2BP1, and that the interaction between IGF2BP1 and PABPC1 promotes AKT2 expression. Finally, following the knockdown of both IGF2BP1 and AKT2, glucose and ATP levels in C18-4 and GC-1 spermatogonia cells were found to be reduced, indicating that IGF2BP1 regulates glucose metabolism homeostasis by stabilizing Akt2 expression, thereby influencing spermatogonia proliferation. Additionally, analysis of the cryptorchidism database from NCBI revealed that the expression of IGF2BP1 and AKT2 is significantly downregulated in cryptorchid patients with oligospermia or azoospermia. In conclusion, our study elucidates the role and underlying mechanism of IGF2BP1 in spermatogonia, providing a candidate target for male infertility.