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Two\u2010dimensional gel electrophoresis (2\u2010DE) and MALDI\u2010TOF\u2010MS analysis identified 10 differentially expressed proteins in stressed rats compared with controls. A strong protein interaction network was found to be centred on Atp5a1 among these proteins. Atp5a1 expression significantly decreased in Leydig cells after chronic stress. Transfection of Atp5a1\u00a0siRNAs decreased StAR, CYP11A1, and 17\u03b2\u2010HSD expression by damaging the structure of mitochondria in TM3 cells. This study confirmed that chronic stress plays an important role in testosterone synthesis by regulating Atp5a1 expression in Leydig cells.<\/jats:p>","DOI":"10.1111\/jcmm.17085","type":"journal-article","created":{"date-parts":[[2021,12,11]],"date-time":"2021-12-11T06:39:56Z","timestamp":1639204796000},"page":"354-363","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Chronic stress inhibits testosterone synthesis in Leydig cells through mitochondrial damage via Atp5a1"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8793-2713","authenticated-orcid":false,"given":"Xiaofan","family":"Xiong","sequence":"first","affiliation":[{"name":"Western China Science and Technology Innovation Port in Precision Medicine Institute The Second Affiliated Hospital of Xi'an Jiaotong University Xi'an China"},{"name":"Department of Cell Biology and Genetics, School of Basic Medical Sciences 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