Asian journal of andrology最新文献

{"title":"Gestational sleep deprivation-induced changes in serum hormone concentrations and testicular oxidative stress affect spermatogenesis in postpubertal male offspring of mice.","authors":"Xin-Yang Zhang, Kai Wang, Han Li, Qian-Qian Cui, Ying-Jun Li, Dan-He Zhao, Tao Bai, Li Wang","doi":"10.4103/aja202581","DOIUrl":"10.4103/aja202581","url":null,"abstract":"<p><p>Maternal sleep deprivation (SD) during pregnancy is prevalent and associated with adverse outcomes. However, the effect of SD on reproductive development in postpubertal male offspring remains incompletely understood. We investigated the effects of maternal SD during mid-gestation (gestational day 8 to delivery) and late gestation (gestational day 15 to delivery) on reproductive development in a 8-week-old male offspring of C57BL/6J mice. We analyzed the underlying oxidative stress mechanisms implicated in these effects. SD was induced for 16 h per day using the modified multiple platform method. Sperm parameters of the offspring ( n = 8 per group) were analyzed, including serum reproductive hormones (testosterone, follicle-stimulating hormone, and luteinizing hormone), testicular oxidative stress markers (superoxide dismutase and malondialdehyde), and key proteins in the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of the rapamycin (PI3K/Akt/mTOR) signaling pathway. Among the offspring, the mid-gestation SD (MSD) group showed significantly lower sperm count, sperm motility, and follicle-stimulating hormone concentrations than the respective control groups (all P < 0.05). The late-gestation SD (LSD) group showed lower luteinizing hormone concentrations than the control group ( P < 0.05). Testosterone, follicle-stimulating hormone, and luteinizing hormone concentrations were lower in the MSD group than those in the LSD group (all P < 0.05). Superoxide dismutase activity was lower in the MSD group than that in the control group ( P < 0.05). No significant changes were observed in PI3K/Akt/mTOR pathway protein expression. In conclusion, maternal SD, particularly from mid-gestation to delivery, impairs spermatogenesis in postpubertal male offspring, which may be mediated through sex hormone dysregulation and testicular oxidative stress.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"409-415"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biallelic variants in TBC1D8 are potentially associated with male infertility due to non-obstructive azoospermia or cryptozoospermia.","authors":"Yi-Lin Sang, Yao Peng, Chao-Feng Tu, Ge Lin, Guang-Xiu Lu, Juan Du, Fu-Yan Wang, Yue-Qiu Tan, Lv-Jun Liu, Wen-Bin He","doi":"10.4103/aja202577","DOIUrl":"10.4103/aja202577","url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) and cryptozoospermia are two significant conditions contributing to male infertility. However, the underlying genetic factors in most cases remain unknown. In our study, whole exome sequencing identified novel biallelic variants in TBC1 domain family member 8 (TBC1D8) in two patients. Patient P1 with NOA harbored c.890C>T (p.A297V) and c.2461G>A (p.V821I), and patient P2 with cryptozoospermia carried c.854C>T (p.P285L) and c.1912G>A (p.D638N). Bioinformatic analyses predicted that all identified TBC1D8 variants were likely pathogenic. Compared with a normal control, patient P1 showed reduced expression of TBC1D8 in testicular tissue. Subsequently, hematoxylin-eosin staining and immunofluorescence analysis of testicular sections showed defective acrosome formation and the absence of elongated spermatids in patient P1, resulting from abnormal autophagy. Additionally, intracytoplasmic sperm injection treatment was beneficial for patient P2 with cryptozoospermia. In conclusion, our results suggest that TBC1D8 is a potentially novel candidate gene for male infertility associated with NOA or cryptozoospermia in humans.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"392-397"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNAs profiles in seminal plasma: a bioinformatic insight into pathways and gene networks involved in non-obstructive azoospermia (NOA).","authors":"Gabriel Maldonado, Marcelo Marconi, Ricardo D Moreno","doi":"10.4103/aja202554","DOIUrl":"10.4103/aja202554","url":null,"abstract":"<p><p>Non-obstructive azoospermia (NOA) is characterized by the absence of spermatozoa in the ejaculate as a result of impaired spermatogenesis. MicroRNAs (miRNAs), a type of small non-coding RNAs, have emerged as promising biomarkers owing to their remarkable stability in biological fluids. This systematic review examines miRNA expression profiles reported in seminal plasma and testicular tissue from patients with NOA. From an initial set of 1061 records, 14 studies met stringent inclusion criteria. A total of 73 unique miRNAs were identified. Among these, six miRNAs were consistently downregulated, and only one miRNA, hsa-miR-31-5p, was consistently upregulated in the seminal plasma of NOA patients compared to fertile controls. Bioinformatic analysis revealed a regulatory network involving three downregulated miRNAs (hsa-miR-34c-5p, hsa-miR-34b-3p, and hsa-miR-202-3p) that converge on two key target genes: interleukin 6 receptor (IL6R) and secretion-associated ras-related GTPase 1A (SAR1A), which are implicated in inflammation and intracellular vesicle transport, respectively. Pathway enrichment analyses indicated that the target genes of dysregulated miRNAs were enriched in cancer-related pathways and processes involving nucleic acid metabolism. Given the reported increased cancer risk among azoospermic patients, these findings suggest that specific miRNAs in seminal plasma may serve as novel non-invasive biomarkers and point to shared molecular mechanisms potentially linking NOA and cancer etiology.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"382-391"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A narrative review on the role of autophagy in male infertility-associated sperm abnormalities.","authors":"Yi-Han Jin, Da-Wei Gao, Chu-Yu Li, Da-Lin Sun, Hui Mo, Bao-Fang Jin","doi":"10.4103/aja202589","DOIUrl":"10.4103/aja202589","url":null,"abstract":"<p><p>Male infertility is one of the most prevalent disorders affecting the male reproductive system, with the majority of cases originating from sperm abnormalities. Autophagy, a highly conserved cellular process, plays critical roles in spermatogenesis, sperm maturation, and functional maintenance. Aberrant autophagic activity is closely associated with various sperm abnormalities, including oligozoospermia, asthenozoospermia, teratozoospermia, and azoospermia. In this narrative review, we provide a comprehensive overview of the current knowledge on the role of autophagy in sperm abnormality-related male infertility, detailing the relationship between autophagic dysfunction and various sperm disorders. We compile and synthesize findings from major clinical studies, basic science research, and relevant reviews to highlight the role of autophagy and its therapeutic potential. These insights may contribute to advancing the clinical management of male infertility through the identification of novel therapeutic targets related to autophagic regulation.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"359-368"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423387/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative sperm proteomics in IVF patients with differential fertilization rates identifies FAM205A as a novel biomarker for male infertility.","authors":"Peng Zhang, He-Mei Li, Sai Lu, Li-Qing Fan, Hui Qian, Jiu Yin","doi":"10.4103/aja202580","DOIUrl":"10.4103/aja202580","url":null,"abstract":"<p><p>This study identified family with sequence similarity 205, member A (FAM205A) as a clinically significant acrosomal protein critically implicated in male idiopathic infertility. Integrated proteomic analysis of sperm from in vitro fertilization (IVF) patients categorized by fertilization outcome ( n = 12 per group; clinical validation, n = 267) revealed a strong correlation between FAM205A expression and fertilization success (76.3% in high-expression groups vs 15.4% in low-expression groups, P < 0.05), independent of standard semen parameters. Functional analyses utilizing pooled human sperm samples ( n = 20 per group) revealed that low FAM205A expression led to a significantly decreased calcium-induced acrosome reaction response (28.9% vs 49.2% in high FAM205A expression, P < 0.01), a phenotype corroborated by anti-FAM205A antibody blockade (38.1% inhibition, P < 0.01). The clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) genome editing system (CRISPR-Cas9)-generated knockout mice lacking Fam205a1 , which is the murine ortholog of human FAM205A, exhibited complete infertility, characterized by oligospermia, asthenozoospermia, teratozoospermia, disrupted acrosome formation, and significantly reduced sperm motility. Mechanistic studies in Fam205a1 knockout mice revealed that FAM205A deficiency induces spermatid apoptosis and impairs acrosomal exocytosis, a crucial process for sperm-egg fusion. The results demonstrate that FAM205A regulates fertility through two mechanisms: preserving structural integrity during spermiogenesis and facilitating the acrosomal reaction (AR). This study identified FAM205A as a reliable diagnostic biomarker for idiopathic male infertility and a potential treatment target in reproductive medicine.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"454-466"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147876749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Male testosterone synthesis disorders: oxidative stress pathways, regulatory mechanisms, potential of antioxidant therapy, and botanical medicine prospects.","authors":"Hui Wu, Min-Tao Jian, Gang Ning, Bo-Nan Li, A-Jian Peng, Hao-Yu Wang, Xue Tang, Xing Zhou","doi":"10.4103/aja2025105","DOIUrl":"10.4103/aja2025105","url":null,"abstract":"<p><p>Testosterone, one of the most important hormones in men, regulates many physiological and pathological processes. Testosterone biosynthesis mainly occurs in Leydig cells. Oxidative stress (OS) is also commonly observed in Leydig cells and is an important factor, leading to decreased testosterone concentrations. This review evaluates male testosterone synthesis disorders from the perspective of OS. OS impairs testosterone synthesis through multiple mechanisms, including modulating the function of the hypothalamic-pituitary-gonadal axis, reducing testicular steroid synthase activity, damaging the mitochondrial function of Leydig cells, inducing endoplasmic reticulum stress, and inhibiting Leydig cell development. A coordinated regulatory network comprising nuclear factor erythroid-2-related factor 2 (Nrf2), sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1 α ), and the glutathione pathway, plays an integral role in modulating testosterone biosynthesis. We summarize the therapeutic potential of antioxidants, especially botanical medicines, in mitigating Leydig cell oxidative injury and restoring testosterone biosynthesis, highlighting their promise as a novel treatment approach. Finally, the therapeutic potential of antioxidants in male disorders of testosterone synthesis, including late-onset hypogonadism, male infertility, and erectile dysfunction, is systematically reviewed and critically analyzed. This review provides a deeper understanding of the mechanisms underpinning testosterone synthesis disorders and may facilitate the development of new clinical treatments.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"369-381"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423390/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147596979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extraperitoneal single-port robot-assisted radical prostatectomy using da Vinci Xi platform: learning curve and outcome analysis.","authors":"Li-Chen Chen, Yan Wang, Xing-Lin Chen, Ming-Yue Tan, Guan-Qun Ju, Dong-Liang Xu","doi":"10.4103/aja202562","DOIUrl":"10.4103/aja202562","url":null,"abstract":"<p><p>This single-center retrospective cohort study evaluated the feasibility, safety, and learning curve of extraperitoneal single-port robot-assisted radical prostatectomy using the da Vinci Xi platform for localized prostate cancer. The data of 200 consecutive patients with localized prostate cancer who underwent this procedure by a single surgeon at Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Shanghai, China) from June 2021 to January 2023 were collected. Key outcomes included operative time, estimated blood loss, complications, biochemical recurrence, and continence recovery. A cumulative sum analysis identified three learning phases: initial learning (≤50 cases), consolidation (51-155 cases), and proficiency (>155 cases). Across phases, operative time decreased by 19.5% (from 174 min to 140 min), estimated blood loss decreased by 40.9% (from 115 ml to 68 ml), and positive surgical margin rate decreased by 61.1% (from 35.2% to 13.7%). At 12 months, 98.0% of the patients achieved continence, and 5.0% experienced biochemical recurrence. Minor complications occurred in 8.5% of the cases, with no severe events reported. Despite its technical challenges and steep learning curve, the extraperitoneal single-port robotic prostatectomy using the da Vinci Xi platform was observed to be safe, feasible, and reproducible, yielding favorable perioperative, functional, and oncological outcomes, even during the initial phase of skill acquisition.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"447-453"},"PeriodicalIF":2.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13423382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of erectile dysfunction in type 1 and type 2 diabetic rats: a multiomics approach.","authors":"Cheng Cheng, Xing-Jun Bao, Jing-Bang Liu, Lei Zheng, Le-Tian Wei, Zhi-Min Wen, Wen-Rong Liu, Hui Jiang, Tao Jiang","doi":"10.4103/aja20267","DOIUrl":"https://doi.org/10.4103/aja20267","url":null,"abstract":"<p><p>Erectile dysfunction (ED) is a prevalent complication of both type 1 and type 2 diabetes mellitus (DM), but the shared molecular mechanisms underlying this complication remain unclear. This study employed an integrative multiomics approach to identify conserved pathways in diabetic ED. A type 2 diabetes mellitus-related erectile dysfunction (T2DM-ED) rat model was established and validated functionally. Transcriptomic analysis of cavernous tissue identified differentially expressed genes (DEGs), which were cross-referenced with a public type 1 diabetes mellitus-related erectile dysfunction (T1DM-ED) dataset, revealing 141 shared DEGs enriched in extracellular matrix (ECM)-receptor interaction, focal adhesion, phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt), and advanced glycation end products (AGE)-receptor for advanced glycation end products (RAGE) signaling. Machine learning prioritized five consistently downregulated hub genes (periostin [POSTN], elastin [ELN], collagen type VI alpha 3 chain [COL6A3], collagen type V alpha 2 chain [COL5A2], and secreted protein acidic and rich in cysteine [SPARC]), as validated by quantitative polymerase chain reaction (qPCR) and Western blot. Their encoded proteins (periostin, elastin, collagen VI, collagen V, and SPARC) were significantly suppressed. Further analysis revealed downregulation of the expression of the focal adhesion kinase (FAK)-PI3K-Akt survival pathway and brain-derived neurotrophic factor (BDNF) and increased apoptosis (cleaved caspase-3) and CD68+ macrophage infiltration. Single-cell RNA sequencing (scRNA-seq) mapping localized these hub genes to stromal and neural cells. These findings reveal a pathological microenvironment of ECM imbalance, impaired survival signaling, and inflammation, which are common to both diabetic ED subtypes. We conclude that macrophage-driven inflammation and ECM disruption converge to inhibit FAK-PI3K-Akt signaling, accelerating structural and functional decline. This inflammatory-ECM signaling axis represents a promising therapeutic target for diabetic ED.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148364328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The long (GGN)n repeat tract in the androgen receptor gene exerts a negative effect on quantitative sperm parameters.","authors":"Kristel Ehala-Aleksejev, Triin Kikas, Marina Grigorova, Tiina Kahre, Olev Poolamets, Vladimir Vihljajev, Kristjan Pomm, Margus Punab, Maris Laan","doi":"10.4103/aja202612","DOIUrl":"https://doi.org/10.4103/aja202612","url":null,"abstract":"<p><p>Androgens act through the androgen receptor (AR), which regulates nearly a thousand genes. The human AR gene contains polymorphic repeats, including (CAG)n and (GGN)n, which affect AR transactivation. This study investigated their independent and combined effects on reproductive and general health. The study included 866 patients with male factor infertility (mean age: 32.8 years, and standard deviation: 6.8 years). Standard protocols were followed for semen analysis, phenotyping, and laboratory data collection. Repeat numbers of (CAG)n and (GGN)n polymorphisms were detected simultaneously using an established genotyping assay. Significantly lower sperm counts were observed in carriers of the AR gene with ≥24 compared to ≤22 GGN repeats (median: 13.5 × 106 vs 18.2 × 106 per ejaculate, P < 0.01). The meta-analysis with the Baltic young men cohort confirmed this association (n = 1843; linear regression: β = -0.38 × 106 [95% confidence interval, 95% CI: -0.75 × 106 to -0.01 × 106] per ejaculate, P = 0.044). The effect was further enhanced by long AR (CAG)n tract (≥25 repeats). The lowest sperm counts (median: 13.6 × 106 per ejaculate) and concentrations (3.5 × 106 ml-1) were detected in carriers of the AR haplotype combining ≥24 GGN and ≥25 CAG repeats (6.8% of patients). For AR (CAG)n repeats, a positive association was observed only with body mass index (BMI; P = 0.02). Neither AR repeat stretch affected semen volume, serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, glucose, lipids, uric acid, or C-reactive protein (CRP) levels. In conclusion, an increased AR (GGN)n repeat number exerts a pronounced negative modulatory effect on sperm parameters. To date, only a limited number of common genetic variants have been reported to be associated with quantitative sperm parameters.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148304278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring potential targets and mechanisms of male reproductive toxicity induced by the emerging PFAS GenX and F-53B via network toxicology, molecular docking, and in vivo validation.","authors":"Qi-Xuan Zhou, Yi-Jun Yang, Xiao-Zhe Su, Heng Xiang, Cai-Tao Dong, Si-Xing Yang","doi":"10.4103/aja202613","DOIUrl":"https://doi.org/10.4103/aja202613","url":null,"abstract":"<p><p>Epidemiological studies have reported a progressive decline in parameters of male reproductive health. Increasing evidence has linked this decline to environmental contaminants. Per- and polyfluoroalkyl substances (PFAS), a major class of synthetic organic chemicals containing fully or partially fluorinated alkyl chains, are one of important environmental contaminants. In China, hexafluoropropylene oxide dimer acid (GenX) and chlorinated polyfluoroalkyl ether sulfonic acids (F-53B) are predominant PFAS. Reproductive toxicity of PFAS has been well-supported by evidence. However, evidence on male reproductive toxicity induced by GenX and F-53B remains limited. The present study aimed to explore the potential molecular targets and mechanisms of male reproductive toxicity induced by GenX and F-53B. Utilizing network toxicology, the intersection of targets between GenX and F-53B and male reproductive toxicity was identified. Their Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathways were further analyzed. Next, four core genes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), tumor necrosis factor (TNF), MYC proto-oncogene (MYC), and estrogen receptor 1 (ESR1), were selected, and their relationships with the primary enrichment results were examined. Molecular docking and binding energy analysis were used to support strong interactions between the compounds and the core genes. The involvement of the core genes in toxic effects caused by GenX and F-53B was further supported by in vivo evidence. Overall, an integrated framework combining network toxicology, molecular docking, and in vivo validation was used to demonstrate male reproductive toxicity associated with GenX and F-53B. Mechanistic hypotheses were generated that may inform future investigations and clinical risk mitigation strategies.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2026-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148213736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}