Male infertility is recognized as a multidimensional health issue that covers the physiological, psychological, social, and cultural factors. Despite the availability of prior literature on infertility, the role of religion and spirituality in understanding and coping with male infertility has remained unexplored. This gap is particularly pronounced in Muslim societies such as Pakistan, where religious beliefs significantly shape individuals' health experiences and coping strategies. This study explores how religious beliefs and spiritual practices shape the experiences of Muslim men dealing with infertility. This qualitative study employed a purposive sampling technique to collect data from 13 infertile Muslim men residing in Lahore, Pakistan. The authors conducted a thematic analysis of the data. The findings showed that the respondents believe Allah (God) has control over their fertility and express hope that divine intervention could bring positive change to their lives. They also expressed a belief that evil spirits are obstructing their fertility, physical well-being, and personal progress. To cope with emotional distress and suffering, they engage in various religious and spiritual practices, including prayer (dua), charity (sadaqah), and visiting shrines to perform rituals. These religious coping practices serve as a source of resilience, hope, and emotional support, allowing respondents to find solace in their faith and overcome psychological challenges. Additionally, this research contributes to understanding the male infertility experiences within the context of religion and spirituality. Futureresearch should examine the therapeutic rituals that Muslim men practice for addressing infertility. Researchersshould also conduct a comparative analysis of various religious groups, such as Christianity and Hinduism, to explore the similarities and differences in infertility experiences and coping strategies across these religions.

Male infertility, often caused by structural and functional sperm defects, remains genetically unexplained in a substantial proportion of cases. ATP1A4 encodes a testis-specific isoform of the Na+, K+-ATPase, a membrane enzyme crucial for maintaining cellular ionic homeostasis. Previous studies on Atp1a4 knockout mice have demonstrated severe defects in sperm motility and flagellar architecture; however, the contribution of ATP1A4 variants to human male reproduction remains to be elucidated. In this study, we identified compound biallelic variants in ATP1A4, a missense variant (c.2578 T>A, p.Tyr860Asn) and a frameshift variant (c.2582del, p.Gly861Aspfs*5), in a patient presenting with severe oligoasthenoteratozoospermia. Both variants markedly affected ATP1A4 protein expression. Morphological analyses revealed coiled and folded flagella, disrupted mitochondrial sheaths, and irregular head morphology in the patient's spermatozoa. Expression profiling revealed that ATP1A4 was highly enriched in post-meiotic spermatids and localized along the entire flagellum of mature sperm in both humans and mice, indicating a critical role in flagellar assembly and structural integrity. Notably, intracytoplasmic sperm injection (ICSI) in this patient resulted in low fertilization efficiency and failed implantation, suggesting a potential adverse impact of ATP1A4 deficiency on sperm functional competence beyond motility. These findings broaden the genetic spectrum of oligoasthenoteratozoospermia and highlight ATP1A4 as a potential gene associated with human male infertility.

Male Infertility.

Extracorporeal photopheresis preserves fertility in a GVHD mouse model by remodeling the testicular immune microenvironment.

Mechanistic insights into sperm cyclic adenosine monophosphate (cAMP) signaling: Relevance for male infertility and contraceptive development.

Despite extensive research, a consolidated synthesis of electrolyte regulation and related channelopathies in sperm biology remains limited. This scoping review maps global evidence on ionic homeostasis and male fertility. Following PRISMA-ScR guidelines, searches were conducted in PubMed, Scopus, and Web of Science for studies published between January 2000 and August 2025. A total of 210 studies were reviewed. Publications were dominated by China (25.71%), Nigeria (8.57%), and the United States (8.57%), followed by Egypt (5.24%), Germany (4.76%), India (4.29%), and Spain (4.29%), with additional contributions from more than 30 countries spanning Europe, Asia, Africa, and the Americas. Core ion channels, including CatSper, SLO3, TRPV6, CFTR, ClC-2, Na+/H+ exchangers, and aquaporins, were consistently associated with pH regulation, calcium signaling, and membrane potential essential for fertilization. Mutations in the CFTR, ADGRG2, TRPV6, and SLO3 genes were implicated in congenital or idiopathic infertility. Environmental, metabolic, and toxicological stressors, including heavy metals and oxidative imbalance, disrupted ionic homeostasis and impaired sperm quality. Ion-channel regulation and electrolyte balance are essential for sperm function. Integrating genetic, physiological, and toxicological evidence highlights key biomarkers and therapeutic targets, emphasizing the need for channel-focused interventions and broader global research representation.

Mesenchymal Stem Cell Transplantation as a Therapeutic Strategy to Preserve Testicular Integrity and Counteract Microgravity-Induced Male Infertility.

In mammals, the epididymis is composed of pseudostratified epithelium that forms the post-testicular milieu for spermatozoa. To date, the role of epithelial cells in shaping the luminal microenvironment for spermatozoa remains poorly understood. Here, we generated a conditional knockout mouse model of Nudt21 in the epididymis, the key component of mammalian cleavage factor I (CFIm) that participates in the 3'end processing of pre-mRNAs. We found that Nudt21 deletion occurred mainly in principal cells of the corpus and the cauda. The loss of NUDT21 in principal cells resulted in male infertility, owing to sperm abnormalities present in the cauda. Pseudotime analysis revealed that the differentiation of Nudt21-null principal cells was blocked, preventing them from exerting the physiological function. Amid transcripts with shortened 3' untranslated regions (3'UTRs) after Nudt21 deletion, Dicer1 transcripts not only had shortened 3'UTR, but also skipped the exon 1, resulting in down-regulation of full length DICER1 protein. Together, these results demonstrate the essential role of NUDT21-mediated 3'UTR dynamics in preserving sperm integrity, and provide insights into the intricate communication between the epididymal epithelium and spermatozoa.

In the field of male health, disorders of the reproductive and urological systems present significant challenges. The global increase in male infertility, primarily attributed to environmental and lifestyle factors, along with the high incidence of urological cancers, not only places a significant socio-economic burden but also emphasizes the urgent need for in-depth research. Epigenetic modifications, especially N6-methyladenosine (m6A) methylation, are of great importance in these conditions. m6A, which is regulated by specific "writer", "eraser", and "reader" proteins, has an impact on various RNA-related processes. This review summarizes the regulatory functions of m6A in male reproductive health and urological cancers. In male reproduction, it explores how m6A affects somatic cell functions, steroidogenesis, and the blood-testis barrier. It also delves into its role in diabetic erectile dysfunction and benign prostatic hyperplasia. In urological cancers, the review examines m6A's influence on metabolic reprogramming, programmed cell death, and tumor immunity. Furthermore, this review discusses the potential of targeting m6A as a therapeutic approach for these conditions. By integrating recent research findings, it offers new perspectives on the role of m6A in male reproductive and urological disorders, laying a foundation for future research.

Infertility affects an estimated 15% of couples worldwide, with male factors contributing to nearly half of the cases. Yet infertility continues to be culturally framed as a woman's problem, positioning women as primary targets of medical investigation and social blame. This study employs a Critical Interpretive Synthesis across sociology, nursing, psychology, anthropology and bioethics to theorise male infertility stigma as a relational inequity rather than an individual burden. To strengthen the empirical grounding of this conceptual analysis, we incorporated a structured secondary analysis of published qualitative quotations from men experiencing infertility. These first‑order accounts illuminate how men narrate stigma, masculinity and relational strain, providing empirical illustrations of four relational mechanisms-concealment, blame transfer, emotional labour and role reconfiguration-through which men's spoiled masculinity invisibly restructures women's roles in reproductive care. By foregrounding women's invisible burdens, the analysis advances a relational sociology of health with direct implications for nursing practice. The findings demonstrate how nurses encounter and mediate stigma spillover in clinical encounters, family systems and community contexts. Applied implications include dyadic, stigma‑sensitive interventions, couple‑centred care pathways and structural reforms that challenge cultural scripts linking masculinity to fertility. Conceptualising infertility stigma as a relational inequity not only extends stigma theory but also strengthens nursing inquiry into gender, caregiving and reproductive justice.

Varicocele: new perspectives on an old problem.

License to bind: Role of glycoproteins in male (in)fertility.

Mitochondrial-derived peptide MOTS-c targets SLC7A11 to preserve spermatogenesis by suppressing ferroptosis.

One of the main causes of the increasing male infertility today is di-(2-ethylhexyl) phthalate (DEHP), which is widely used in plastic production. To investigate testicular damage caused by DEHP and the effect of galangin, used for the first time in this treatment, the protective effect of different doses of galangin on testicular damage induced by administering DEHP for 14 days to 54 Sprague Dawley rats aged 8-10 weeks was examined. For this purpose, experimental groups were designed as follows: (Control: no treatment applied, Solvent: 5 mL/kg/day corn oil applied, Phthalate (PHT): 2 g/kg DEHP applied, Galangin GL-5, GL-10 and GL-15: galangin applied at doses of 5, 10 and 15 mg/kg, respectively, PHT + GL-5, PHT + GL-10 and PHT + GL-15: galangin applied at doses of 5, 10 and 15 mg/kg, respectively, 1 h after 2 g/kg DEHP dissolved in 5 mL/kg corn oil). After the experimental process was completed, histopathological and immunohistochemical analyses were performed on tissue samples taken from decapitated rats. Malondialdehyde (MDA), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) analyses were performed on tissue and serum samples, and spermatological analyses were also conducted. In the PHT group, changes in light microscopic findings in the testes (degeneration in seminiferous tubules, interstitial oedema, interstitial vascular hyperaemia) and a decrease in Johnsen scoring, seminiferous tubule diameters and epithelial thickness were observed. It was determined that galangin administration, with increasing doses, led to significant improvements in histopathological parameters. When the immunoreactivity of Hydroxy-Delta-5-Steroid Dehydrogenase, 3 Beta- and Steroid Delta-Isomerase 1 (HSD3B1), and the sex-determining region Y-box9 (Sox9) was examined in testicular tissues, a decrease was observed in the PHT groups and an increase in the GL groups. In the PHT group, plasma and testicular tissue MDA levels were higher compared to the control and other groups, while GSH, CAT, GSH-Px, SOD and GST levels were lower. In the GL groups, the opposite effect was observed in these parameters compared to the PHT group. In spermatological analyses, it was observed that the negative effects in some parameters (gonado-somatic index [GSI], density, total motility, acrosomal damage rate, mitochondrial membrane potential, morphological values) observed in the PHT groups decreased and disappeared in a dose-dependent manner in the galangin-treated groups. This study confirmed that galangin improved testicular damage caused by DEHP exposure, providing strong evidence for the use of galangin in the treatment of DEHP-related infertility.

Y-chromosome microdeletions, particularly in the azoospermia factor c (AZFc) region, are a common genetic cause of male infertility. This study evaluates sperm retrieval rates (SRRs) and testicular histology across age groups in men with isolated AZFc deletions. We identified men with isolated complete AZFc microdeletions who underwent microdissection testicular sperm extraction from 2000 to 2024. Genitourinary pathology reports categorized histology as Sertoli cell-only, tubular atrophy, maturation arrest, or hypospermatogenesis. χ2 tests compared histology and SRR. Multivariable logistic regression assessed factors associated with successful sperm retrieval. Of 1473 patients who underwent Y-chromosome microdeletion testing, 72 with isolated AZFc microdeletions underwent microdissection testicular sperm extraction. Patients were stratified by age 35 years or younger (n = 51) and older than 35 years (n = 21). Overall, germ cells were identified in 59.7% of cases, with no difference between patients 35 years or younger (58.8%) and older than 35 years (61.9%; P = .81). The overall SRR was 50%, with no difference by the age group (≤35 years: 51.0%, older than 35 years: 47.6%; P = .80). On multivariable analysis, age older than 35 years (odds ratio [OR] 0.82, 95% CI [0.28-2.40]) and the presence of spermatogenesis during biopsy (OR 1.66, 95% CI [0.59-4.69]) were not associated with SRR. Follicle-stimulating hormone levels between 12.4 and 24.0 mIU/mL were associated with higher SRR (OR 7.04, 95% CI [1.83-27.1]). Patient age was not a strong predictor of sperm retrieval success in men with complete AZFc deletion. Follicle-stimulating hormone levels within an intermediate range were associated with higher SRRs, suggesting that hormonal context may inform patient counseling. Reproductive urologists should counsel patients that age alone is unlikely to meaningfully influence sperm retrieval.

Testicular development is a highly orchestrated process essential for male fertility, but its temporal genetic regulation remains incompletely resolved in many mammalian models. This study re-analyses rat testis transcriptomes across 15 stages from embryonic day 12 to postnatal week 16 using bulk RNA-sequencing data from a multispecies organ development atlas, generating a continuous, testis-focused temporal framework, and pinpointing key developmental transition windows and regulatory modules. Of 23,748 annotated genes, 17,717 were differentially expressed (DEGs), and hierarchical plus co-expression analyses identified four principal expression modules and five clusters capturing spermatogenic, morphogenetic, immune, and neurone-like programs. Four major transcriptional transition windows, embryonic day 14, embryonic day 19, postnatal week 2, and postnatal week 6, were defined, with the largest remodeling between 2 and 6 weeks coinciding with the onset of robust spermatogenesis and marking a particularly vulnerable window for environmental or toxicant-induced perturbation. Stage-specific spermatogenesis-associated gene sets at embryonic day 19 (n = 28), postnatal week 2 (n = 61), and week 6 (n = 735) showed minimal overlap, supporting sequential regulatory waves driving germ cell commitment, early meiosis, and terminal differentiation. Target enrichment analyses highlighted five conserved microRNAs (rno-miR-151-5p, rno-miR-29b-3p, rno-miR-384-5p, rno-miR-500-5p, rno-miR-672-5p) whose predicted and validated targets form modules related to extracellular matrix remodeling, apoptosis and cell-cycle control, ion-channel signaling, and neuronal-like pathways, with high sequence conservation to human homologs. Immune-related genes and blood-testis barrier components displayed coordinated expression dynamics, and a conserved core of 487 spermatogenesis genes showed strong cross-mammalian orthology, indicating a deeply shared transcriptional backbone on which species-specific regulatory nuances are layered. This multistage transcriptomic analysis delineates major developmental transitions, co-expression modules, and regulatory miRNA-mRNA networks that orchestrate rat testis maturation and highlight a critical P2W-P6W transition window. The resource complements existing multiorgan and single-cell datasets by providing a testis-focused temporal framework and identifies conserved gene sets and regulatory candidates of direct relevance to male infertility, toxicology, and cross-species translational studies.

During meiotic prophase I, mammalian spermatocytes must synthesize large amounts of recombination and synapsis proteins despite global transcriptional suppression at the leptotene/zygotene (L/Z) stages. Here, we identify eukaryotic translation elongation factor 1 gamma (eEF1G), highly expressed in spermatogenic cells, as a factor essential for sustaining translation during this transcriptionally quiescent period. Germ cell-specific Eef1g knockout causes complete male infertility due to zygotene arrest, characterized by defects in recombination intermediate stabilization and synapsis. Mechanistically, eEF1G associates with ribosomal proteins, and ribosome profiling reveals increased ribosome occupancy on specific meiotic transcripts in Eef1g-deficient spermatocytes. Quantitative proteomics further reveals selective depletion of synapsis-related (e.g., SYCP1, SYCE1) and recombination-related proteins (e.g., MSH4, TEX11). Together, these findings demonstrate that eEF1G is required to maintain efficient protein production during the transcriptionally quiescent leptotene/zygotene stages, thereby supporting proper meiotic progression in mammalian spermatocytes.

Effect of naringin and prednisolone treatment on blood-testis barrier in experimental rheumatoid arthritis model.

Novel RHOXF1 mutation causes male infertility by inducing severe oligoasthenozoospermia.

Background: Male infertility is a critical global health issue, often linked to oxidative stress and inflammation. Probiotics, known for modulating gut health, have been proposed as a potential intervention for improving male reproductive health. However, the evidence remains fragmented, necessitating a systematic review to consolidate findings. Objective: This study systematically evaluates the effects of probiotic interventions on sperm parameters, including count, motility, morphology, and DNA integrity, in human and animal models. Methods: Adhering to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines, databases such as PubMed, Scopus, and Cochrane Library were searched up to November 2024. Eligible studies included controlled trials evaluating the effects of probiotics on sperm parameters in humans and animals. Data extraction focused on study design, probiotic species, dosages, intervention durations, and outcomes. The risk of bias (RoB) was assessed using SYRCLE's RoB tool for animal studies and Cochrane RoB for human studies. Results: Fifteen studies (5 humans, 10 animals) met the inclusion criteria. Probiotic species, belonging predominantly to the genera Lacticaseibacillus, Lactiplantibacillus (both formerly Lactobacillus), Limosilactobacillus, and Bifidobacterium, significantly improved sperm count, motility, morphology, and antioxidant markers. Mechanistic insights highlighted reductions in oxidative stress and inflammation, and improvements in communication between the gut and testis. While findings were consistent, heterogeneity in study design and species used was evident. Conclusion: Probiotics show promise in enhancing sperm parameters, mediated through systemic reductions in oxidative stress and inflammation. However, standardized protocols and long-term studies are necessary to validate their efficacy and develop clinical guidelines.