Multi-omics analysis and experimental verification reveal testicular fatty acid metabolism disorder in non-obstructive azoospermia  

作　　者：Zhou Li Yi-Jian Xiang Zhi-Chuan Zou Yu-Ming Feng Hui Wang Wei-Qing Chen Xie Ge Jin-Zhao Ma Jun Jing Bing Yao 

机构地区：[1]Department of Reproductive Medicine,Jinling Hospital,Affiliated Hospital of Medical School,Nanjing University,Nanjing,Jiangsu 210000,China [2]State Key Laboratory of Reproductive Medicine and Offspring Health,Nanjing Medicine University,Nanjing,Jiangsu 211166,China

出　　处：《Zoological Research》2025年第1期177-192,共16页动物学研究(英文)

基　　金：supported by the National Natural Science Foundation of China (U22A20277,81971373);Jiangsu Provincial Medical Key Discipline Cultivation Unit (JSDW202215);333 High-level Personnel Training Project of Jiangsu Province (BRA2019109);Postgraduate Research&Practice Innovation Program of Jiangsu Province (KYCX22_1826)。

摘　　要：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.

关 键 词：Non-obstructive azoospermia Fatty acid metabolism Sertoli cell Multi-omics Single-cell RNA sequencing 

分 类 号：R698.2[医药卫生—泌尿科学]