Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty...Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.展开更多
文摘2025年2月11日,上海交通大学公共卫生学院汪一心研究团队(Reproductive&Environmental Nexus for Extended Wellness,RENEW Lab)与华中科技大学梅素容教授课题组合作,在环境科学领域高水平期刊Environmental Science&Technology上在线发表题目为“Organophosphate esters,sperm mitochondrial DNA copy number,and semen quality:a longitudinal study with repeated measurements”的研究成果。研究者基于自主建立的前瞻性精子库男性队列(n=1385),探究了精子发育不同阶段多种有机磷酸酯(organophosphate ester,OPE)阻燃剂单独与联合暴露对男性精液质量的影响,以及精子线粒体DNA拷贝数的中介作用。结果发现,不同种类OPE阻燃剂单独与联合暴露均影响男性精子活力、密度、总数、正常形态率和精子线粒体DNA拷贝数,且精子发育处于附睾储存期对OPE阻燃剂的暴露最为敏感。中介分析结果提示精子细胞线粒体DNA拷贝数在OPE阻燃剂暴露致精子发育受损过程中起到了重要的介导作用。该研究结果为OPE阻燃剂暴露带来的生殖健康风险评估提供了重要科学依据。
基金supported by the National Natural Science Foundation of China (U22A20277,81971373)Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202215)+1 种基金333 High-level Personnel Training Project of Jiangsu Province (BRA2019109)Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_1826)。
文摘Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA),a severe form of male infertility.However,the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated.Multi-omics analyses,including microarray analysis,single-cell RNA sequencing(scRNA-seq),and metabolomics,were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases.Results identified ACSL6,ACSBG2,and OLAH as key genes linked to fatty acid metabolism dysregulation,suggesting their potential causative roles in NOA.A marked reduction in omega-3 polyunsaturated fatty acids,especially docosahexaenoic acid(DHA),was observed,potentially contributing to the pathological process of NOA.Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction,with PPARG identified as a key transcription factor(TF)regulating this process.Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB)integrity and promoting spermatogenesis via regulation of fatty acid metabolism.These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.
