PMID- 35385208 OWN - NLM STAT- MEDLINE DCOM- 20220609 LR - 20220621 IS - 1522-7278 (Electronic) IS - 1520-4081 (Linking) VI - 37 IP - 7 DP - 2022 Jul TI - Leydig cell function in adult male rats is disrupted by perfluorotetradecanoic acid through increasing oxidative stress and apoptosis. PG - 1790-1802 LID - 10.1002/tox.23526 [doi] AB - Perfluorotetradecanoic acid (PFTeDA) is a long-chain perfluoroalkyl compound with increased applications. Its effect on Leydig cell function and its underlying mechanism remain unclear. Male Sprague-Dawley rats (60 days old) were gavaged with PFTeDA at doses of 0, 1, 5, and 10 mg/kg/day from 60 to 87 days after birth. PFTeDA significantly reduced serum testosterone levels at 1 mg/kg and higher doses, while markedly increasing serum luteinizing hormone level at 10 mg/kg and follicle-stimulating hormone at >/=1 mg/kg. PFTeDA significantly reduced the sperm number at the cauda of epididymis at >/=1 mg/kg. PFTeDA also reduced the number of CYP11A1-positive Leydig cells due to increased apoptosis shown by the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. PFTeDA significantly repressed the expression of Cyp17a1 and Star and their proteins at 1-10 mg/kg, while it increased the expression of Srd5a1 and its protein (an immature Leydig cell biomarker) at 10 mg/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 muM. In conclusion, PFTeDA inhibits the function of Leydig cells by inducing oxidative stress and subsequently stimulating cell apoptosis. CI - (c) 2022 Wiley Periodicals LLC. FAU - Tang, Yunbing AU - Tang Y AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Ying, Yingfen AU - Ying Y AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Zou, Cheng AU - Zou C AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Yan, Haoni AU - Yan H AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Wang, Yiyan AU - Wang Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Li, Huitao AU - Li H AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Li, Xiaoheng AU - Li X AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Xu, Zhangye AU - Xu Z AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Lv, Jieqiang AU - Lv J AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. FAU - Ge, Ren-Shan AU - Ge RS AUID- ORCID: 0000-0002-3448-9823 AD - Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. LA - eng GR - 81730042/NSFC (RSG)/ PT - Journal Article DEP - 20220406 PL - United States TA - Environ Toxicol JT - Environmental toxicology JID - 100885357 RN - 0 (Fluorocarbons) RN - 0 (perfluorotetradecanoic acid) RN - 3XMK78S47O (Testosterone) SB - IM MH - Animals MH - *Apoptosis MH - *Fluorocarbons/adverse effects MH - *Leydig Cells MH - Male MH - *Oxidative Stress MH - Rats MH - Rats, Sprague-Dawley MH - Testis MH - Testosterone/blood OTO - NOTNLM OT - Leydig cells OT - PFTeDA OT - apoptosis OT - oxidative stress OT - testosterone EDAT- 2022/04/07 06:00 MHDA- 2022/06/10 06:00 CRDT- 2022/04/06 12:17 PHST- 2022/02/26 00:00 [revised] PHST- 2022/01/02 00:00 [received] PHST- 2022/03/19 00:00 [accepted] PHST- 2022/04/07 06:00 [pubmed] PHST- 2022/06/10 06:00 [medline] PHST- 2022/04/06 12:17 [entrez] AID - 10.1002/tox.23526 [doi] PST - ppublish SO - Environ Toxicol. 2022 Jul;37(7):1790-1802. doi: 10.1002/tox.23526. Epub 2022 Apr 6.