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Its effect on Leydig cell function and its underlying mechanism remain unclear. Male Sprague\u2013Dawley rats (60\u2009days old) were gavaged with PFTeDA at doses of 0, 1, 5, and 10\u2009mg\/kg\/day from 60 to 87\u2009days after birth. PFTeDA significantly reduced serum testosterone levels at 1\u2009mg\/kg and higher doses, while markedly increasing serum luteinizing hormone level at 10\u2009mg\/kg and follicle\u2010stimulating hormone at \u22651\u2009mg\/kg. PFTeDA significantly reduced the sperm number at the cauda of epididymis at \u22651\u2009mg\/kg. PFTeDA also reduced the number of CYP11A1\u2010positive Leydig cells due to increased apoptosis shown by the terminal deoxynucleotidyl transferase\u2010mediated <jats:styled-content style=\"fixed-case\">dUTP<\/jats:styled-content> nick end labeling (TUNEL) assay. PFTeDA significantly repressed the expression of <jats:italic>Cyp17a1<\/jats:italic> and <jats:italic>Star<\/jats:italic> and their proteins at 1\u201310\u2009mg\/kg, while it increased the expression of <jats:italic>Srd5a1<\/jats:italic> and its protein (an immature Leydig cell biomarker) at 10\u2009mg\/kg. PFTeDA markedly increased testicular malondialdehyde level, while inhibiting antioxidants (SOD1, SOD2, and CAT), triggering oxidative stress, thereby further inducing BAX and CASP3 while inhibiting BCL2, which led to cell apoptosis. PFTeDA also reduced DHH level secreted by Sertoli cells, which indirectly affected Leydig cell function. PFTeDA inhibited testosterone secretion in primary Leydig cells in vitro by increasing reactive oxygen species and inducing apoptosis at 50\u2009\u03bcM. In conclusion, PFTeDA inhibits the function of Leydig cells by inducing oxidative stress and subsequently stimulating cell apoptosis.<\/jats:p>","DOI":"10.1002\/tox.23526","type":"journal-article","created":{"date-parts":[[2022,4,6]],"date-time":"2022-04-06T12:08:20Z","timestamp":1649246900000},"page":"1790-1802","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Leydig cell function in adult male rats is disrupted by perfluorotetradecanoic acid through increasing oxidative stress and apoptosis"],"prefix":"10.1002","volume":"37","author":[{"given":"Yunbing","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingfen","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of 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