Jing-Di Zhang, Xiao-Gang Li, Rong-Rong Wang, Xin-Xin Feng, Si-Yu Wang, Hai Wang, Yu-Tao Wang, Hong-Jun Li, Yong-Zhe Li, Ye Guo
{"title":"Integrated seminal plasma metabolomics and lipidomics profiling highlight distinctive signature of varicocele patients with male infertility.","authors":"Jing-Di Zhang, Xiao-Gang Li, Rong-Rong Wang, Xin-Xin Feng, Si-Yu Wang, Hai Wang, Yu-Tao Wang, Hong-Jun Li, Yong-Zhe Li, Ye Guo","doi":"10.4103/aja2024113","DOIUrl":"https://doi.org/10.4103/aja2024113","url":null,"abstract":"<p><p>Varicocele (VC) is a common cause of male infertility, yet there is a lack of molecular information for VC-associated male infertility. This study investigated alterations in the seminal plasma metabolomic and lipidomic profiles of infertile male VC patients. Twenty infertile males with VC and twenty-three age-matched healthy controls (HCs) were recruited from Peking Union Medical College Hospital (Beijing, China) between October 2019 and April 2021. Untargeted metabolite and lipid profiles from seminal plasma were analyzed using mass spectrometry. Four hundred and seventy-six metabolites and seventeen lipids were significantly different in infertile male VC patients compared to HCs. The top enriched pathways among these significantly different metabolites are protein digestion and absorption, aminoacyl-transfer RNA (tRNA) biosynthesis, and biosynthesis of amino acids. Different key lipid species, including triglyceride (TG), diacylglycerol (DG), ceramides (Cer), and phosphatidylserine (PS), varied between VC and HC groups. The distinct metabolites and lipids were moderately correlated. DL-3-phenyllactic acid is a potential diagnostic biomarker for VC-related male infertility (area under the curve [AUC] = 0.893), positively correlating with sperm count, concentration, and motility. Furthermore, DL-3-phenyllactic acid is the only metabolite shared by all four comparisons (VC vs HC, VC-induced oligoasthenospermia [OAS] vs VC-induced asthenospermia [AS], OAS vs HC, and AS vs HC). DL-3-phenyllactic acid significantly decreased in OAS than AS. Metabolite-targeting gene analysis revealed carbonic anhydrase 9 (CA9) might be the strongest candidate associated with the onset and severity of VC. The seminal plasma metabolite and lipid profiles of infertile males with VC differ significantly from those of HCs. DL-3-phenyllactic acid could be a promising biomarker.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805081","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":"Targeted gene silencing in mouse testicular Sertoli and Leydig cells using adeno-associated virus vectors.","authors":"Jing Pang, Mao-Xing Xu, Xiao-Yu Wang, Xu Feng, Yi-Man Duan, Xiao-Yan Zheng, Yu-Qian Chen, Wen Yin, Ying Liu, Ju-Xue Li","doi":"10.4103/aja2024120","DOIUrl":"https://doi.org/10.4103/aja2024120","url":null,"abstract":"<p><strong>Abstract: </strong>Researchers commonly use cyclization recombination enzyme/locus of X-over P1 (Cre/loxP) technology-based conditional gene knockouts of model mice to investigate the functional roles of genes of interest in Sertoli and Leydig cells within the testis. However, the shortcomings of these genetic tools include high costs, lengthy experimental periods, and limited accessibility for researchers. Therefore, exploring alternative gene silencing techniques is of great practical value. In this study, we employed adeno-associated virus (AAV) as a vector for gene silencing in Sertoli and Leydig cells. Our findings demonstrated that AAV serotypes 1, 8, and 9 exhibited high infection efficiency in both types of testis cells. Importantly, we discovered that all three AAV serotypes exhibited exquisite specificity in targeting Sertoli cells via tubular injection while demonstrating remarkable selectivity in targeting Leydig cells via interstitial injection. We achieved cell-specific knockouts of the steroidogenic acute regulatory (Star) and luteinizing hormone/human chorionic gonadotropin receptor (Lhcgr) genes in Leydig cells, but not in Sertoli cells, using AAV9-single guide RNA (sgRNA)-mediated gene editing in Rosa26-LSL-Cas9 mice. Knockdown of androgen receptor (Ar) gene expression in Sertoli cells of wild-type mice was achieved via tubular injection of AAV9-short hairpin RNA (shRNA)-mediated targeting. Our findings offer technical approaches for investigating gene function in Sertoli and Leydig cells through AAV9-mediated gene silencing.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143675093","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}
Xi-Ren Ji, Rui-Jun Wang, Zeng-Hui Huang, Hui-Lan Wu, Xiu-Hai Huang, Hao Bo, Ge Lin, Wen-Bing Zhu, Chuan Huang
{"title":"Sperm tRNA-derived fragments expression is potentially linked to abstinence-related improvement of sperm quality.","authors":"Xi-Ren Ji, Rui-Jun Wang, Zeng-Hui Huang, Hui-Lan Wu, Xiu-Hai Huang, Hao Bo, Ge Lin, Wen-Bing Zhu, Chuan Huang","doi":"10.4103/aja2024123","DOIUrl":"https://doi.org/10.4103/aja2024123","url":null,"abstract":"<p><strong>Abstract: </strong>Recent studies have shown that shorter periods of ejaculatory abstinence may enhance certain sperm parameters, but the molecular mechanisms underlying these improvements are still unclear. This study explored whether reduced abstinence periods could improve semen quality, particularly for use in assisted reproductive technologies (ART). We analyzed semen samples from men with normal sperm counts (n = 101) and those with low sperm motility or concentration (n = 53) after 3-7 days of abstinence and then after 1-3 h of abstinence, obtained from the Reproductive & Genetic Hospital of CITIC-Xiangya (Changsha, China). Physiological and biochemical sperm parameters were evaluated, and the dynamics of transfer RNA (tRNA)-derived fragments (tRFs) were analyzed using deep RNA sequencing in five consecutive samples from men with normal sperm counts. Our results revealed significant improvement in sperm motility and a decrease in the DNA fragmentation index after the 1- to 3-h abstinence period. Additionally, we identified 245 differentially expressed tRFs, and the mitogen-activated protein kinase (MAPK) signaling pathway was the most enriched. Further investigations showed significant changes in tRF-Lys-TTT and its target gene mitogen-activated protein kinase kinase 2 (MAP2K2), which indicates a role of tRFs in improving sperm function. These findings provide new insights into how shorter abstinence periods influence sperm quality and suggest that tRFs may serve as biomarkers for male fertility. This research highlights the potential for optimizing ART protocols and improving reproductive outcomes through molecular approaches that target sperm function.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660019","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":"Regulation of testosterone synthesis by circadian clock genes and its research progress in male diseases.","authors":"Gang Ning, Bo-Nan Li, Hui Wu, Ruo-Bing Shi, A-Jian Peng, Hao-Yu Wang, Xing Zhou","doi":"10.4103/aja20258","DOIUrl":"https://doi.org/10.4103/aja20258","url":null,"abstract":"<p><strong>Abstract: </strong>The circadian clock is an important internal time regulatory system for a range of physiological and behavioral rhythms within living organisms. Testosterone, as one of the most critical sex hormones, is essential for the development of the reproductive system, maintenance of reproductive function, and the overall health of males. The secretion of testosterone in mammals is characterized by distinct circadian rhythms and is closely associated with the regulation of circadian clock genes. Here we review the central and peripheral regulatory mechanisms underlying the influence of circadian clock genes upon testosterone synthesis. We also examined the specific effects of these genes on the occurrence, development, and treatment of common male diseases, including late-onset hypogonadism, erectile dysfunction, male infertility, and prostate cancer.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143660076","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":"Impact of physical activity on semen quality: a review of current evidence.","authors":"Jing Chen, Jin-Ming Guo, Bang-Jian Jiang, Fan-Yuan Sun, Yong-Cun Qu","doi":"10.4103/aja20252","DOIUrl":"https://doi.org/10.4103/aja20252","url":null,"abstract":"<p><p>A growing global trend indicates a decline in semen quality, with a lack of physical activity identified as one of the contributing factors. Exercise is medication, and numerous studies have explored its effects on semen quality. However, there is no consensus on the most effective type and intensity of exercise for improving semen quality, owing to inconsistent findings across studies. These discrepancies may be attributable to variations in study populations (e.g., healthy versus infertile individuals) and research methodologies (e.g., observational versus interventional studies). This paper reviews the existing literature from the databases PubMed, Web of Science, and Google Scholar, reclassifying articles on their subject and research designs to delineate the relationship between exercise and semen quality. It also summarizes the mechanisms through which exercise influences semen quality, including hormonal regulation, oxidative stress, and inflammatory factors.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625852","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}
Xi-Yan Wu, Jin-Chun Lu, Xin-Hua Peng, Jing-Liang He, Dao Wang, Cong-Ling Dai, Wen-Bing Zhu, Gang Liu, Wei-Na Li
{"title":"Exploration of evaluation criteria based on the biological variation in the external quality assessment for basic semen analysis in China.","authors":"Xi-Yan Wu, Jin-Chun Lu, Xin-Hua Peng, Jing-Liang He, Dao Wang, Cong-Ling Dai, Wen-Bing Zhu, Gang Liu, Wei-Na Li","doi":"10.4103/aja2024118","DOIUrl":"https://doi.org/10.4103/aja2024118","url":null,"abstract":"<p><strong>Abstract: </strong>This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598572","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}
Yi Lu, Jing Wang, Zhong-Lin Cai, Teng-Yan Li, Hong-Jun Li, Bin-Bin Wang
{"title":"Cystic fibrosis-causing variants in Chinese patients with congenital absence of the vas deferens: a cohort and meta-analysis.","authors":"Yi Lu, Jing Wang, Zhong-Lin Cai, Teng-Yan Li, Hong-Jun Li, Bin-Bin Wang","doi":"10.4103/aja2024124","DOIUrl":"https://doi.org/10.4103/aja2024124","url":null,"abstract":"<p><strong>Abstract: </strong>Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598571","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":"A novel homozygous splicing mutation in AK7 associated with multiple morphological abnormalities of the sperm flagella.","authors":"Thomas Greither, Holger Herlyn","doi":"10.4103/aja202479","DOIUrl":"10.4103/aja202479","url":null,"abstract":"","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"276"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303269","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}
Elisabetta Baldi, Giovanni M Colpi, Zhong-Wei Huang, Balasingam Balagobi, Florence Boitrelle, Rupin Shah, Ashok Agarwal
{"title":"High sperm DNA fragmentation - finding a needle in the haystack: tips on selecting the best sperm for ICSI and ART.","authors":"Elisabetta Baldi, Giovanni M Colpi, Zhong-Wei Huang, Balasingam Balagobi, Florence Boitrelle, Rupin Shah, Ashok Agarwal","doi":"10.4103/aja202451","DOIUrl":"10.4103/aja202451","url":null,"abstract":"","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"139-143"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121314","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}
Yu Mao, Jian-Mei Huang, Yu-Wei Chen-Zhang, He Lin, Yu-Huan Zhang, Ji-Yang Jiang, Xue-Mei Wu, Ling Liao, Yun-Man Tang, Ji-Yun Yang
{"title":"Exploring the clinical implications of novel SRD5A2 variants in 46,XY disorders of sex development.","authors":"Yu Mao, Jian-Mei Huang, Yu-Wei Chen-Zhang, He Lin, Yu-Huan Zhang, Ji-Yang Jiang, Xue-Mei Wu, Ling Liao, Yun-Man Tang, Ji-Yun Yang","doi":"10.4103/aja202469","DOIUrl":"10.4103/aja202469","url":null,"abstract":"<p><strong>Abstract: </strong>This study was conducted retrospectively on a cohort of 68 patients with steroid 5 α-reductase 2 (SRD5A2) deficiency and 46,XY disorders of sex development (DSD). Whole-exon sequencing revealed 28 variants of SRD5A2 , and further analysis identified seven novel mutants. The preponderance of variants was observed in exon 1 and exon 4, specifically within the nicotinamide adenine dinucleotide phosphate (NADPH)-binding region. Among the entire cohort, 53 patients underwent initial surgery at Sichuan Provincial People's Hospital (Chengdu, China). The external genitalia scores (EGS) of these participants varied from 2.0 to 11.0, with a mean of 6.8 (standard deviation [s.d.]: 2.5). Thirty patients consented to hormone testing. Their average testosterone-to-dihydrotestosterone (T/DHT) ratio was 49.3 (s.d.: 23.4). Genetic testing identified four patients with EGS scores between 6 and 9 as having this syndrome; and their T/DHT ratios were below the diagnostic threshold. Furthermore, assessments conducted using the crystal structure of human SRD5A2 have provided insights into the potential pathogenic mechanisms of these novel variants. These mechanisms include interference with NADPH binding (c.356G>C, c.365A>G, c.492C>G, and c.662T>G) and destabilization of the protein structure (c.727C>T). The c.446-1G>T and c.380delG variants were verified to result in large alterations in the transcripts. Seven novel variations were identified, and the variant database for the SRD5A2 gene was expanded. These findings contribute to the progress of diagnostic and therapeutic approaches for individuals with SRD5A2 deficiency.</p>","PeriodicalId":93889,"journal":{"name":"Asian journal of andrology","volume":" ","pages":"211-218"},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309351","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}