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BPA has been shown to cause damage to male reproductive system; however, the potential mechanism remains to be investigated. In the present study, BPA exposure decreased the testis and epididymis coefficient, caused a disintegration of germinal epithelium, decreased the density and motility of sperm in the epididymis tissue, and increased the number of abnormal sperm morphology, which indicated that BPA exposure could cause damage to testis. BPA was also shown to induce apoptosis and oxidative stress in the testis tissue. The serum testosterone concentration was decreased in the BPA\u2010treated group, suggesting that BPA could lead to Leydig cell damage. Subsequently, mouse TM3 cell, a kind of mouse Leydig cell line, was utilized to investigate the potential mechanism. Herein, we showed that BPA exposure could inhibit cell viability and induce apoptosis of TM3 cells. Furthermore, oxidative stress in the cells could also be induced by BPA, while the inhibition of oxidative stress by N\u2010acetyl\u2010L\u2010cysteine (NAC), an oxidative stress scavenger, could reverse the inhibition of cell viability and induction of apoptosis by BPA exposure, indicating that oxidative stress was involved in BPA\u2010induced apoptosis of TM3 cells. Finally, RNA\u2010sequencing and real\u2010time PCR were utilized to screen and validate the potential oxidative stress\u2010related genes involving in BPA\u2010induced apoptosis. We found that BPA exposure increased the mRNA levels of oxidative stress\u2010related genes such as\n                    <jats:italic>Lonp1<\/jats:italic>\n                    ,\n                    <jats:italic>Klf4<\/jats:italic>\n                    ,\n                    <jats:italic>Rack1<\/jats:italic>\n                    ,\n                    <jats:italic>Egln1<\/jats:italic>\n                    ,\n                    <jats:italic>Txn2<\/jats:italic>\n                    ,\n                    <jats:italic>Msrb1<\/jats:italic>\n                    ,\n                    <jats:italic>Atox1<\/jats:italic>\n                    ,\n                    <jats:italic>Mtr<\/jats:italic>\n                    , and\n                    <jats:italic>Atp2a2<\/jats:italic>\n                    , as well as decreased the mRNA level of\n                    <jats:italic>Dhfr<\/jats:italic>\n                    gene; while NAC could rescue the expression of these genes. Taken together, oxidative stress was involved in BPA\u2010induced apoptosis of mouse Leydig cells.\n                  <\/jats:p>","DOI":"10.1002\/tox.23690","type":"journal-article","created":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T14:10:40Z","timestamp":1667225440000},"page":"312-321","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Bisphenol A (\n                    <scp>BPA<\/scp>\n                    ) induces apoptosis of mouse Leydig cells via oxidative stress"],"prefix":"10.1002","volume":"38","author":[{"given":"Meijuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences Nanchang University  Nanchang People's Republic of China"},{"name":"School of Public Health Nanchang University  Nanchang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingchun","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences Nanchang University  Nanchang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences Nanchang University  Nanchang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3440-544X","authenticated-orcid":false,"given":"Jinglei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Basic Medical Sciences Nanchang University  Nanchang People's Republic of 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