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Bisphenol S stimulates Leydig cell proliferation but inhibits differentiation in pubertal male rats through multiple mechanisms.
Pan, Peipei; Wen, Zina; Ma, Feifei; Lei, Zhen; Pan, Chengshuang; Fei, Qianjin; Tian, Erpo; Wang, Yiyan; Zhu, Qiqi; Li, Huitao; Li, Xiaoheng; Zhong, Ying; Ge, Ren-Shan; Xu, Ren-Ai.
Afiliación
  • Pan P; Department of Reproductive Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Wen Z; Department of Andrology, Chengdu Xi'nan Gynecological Hospital, Chengdu, China.
  • Ma F; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Lei Z; Department of Andrology, Chengdu Xi'nan Gynecological Hospital, Chengdu, China.
  • Pan C; Department of Reproductive Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Fei Q; Department of Reproductive Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Tian E; Department of Andrology, Chengdu Xi'nan Gynecological Hospital, Chengdu, China.
  • Wang Y; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Zhu Q; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Li H; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Li X; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Zhong Y; Department of Andrology, Chengdu Xi'nan Gynecological Hospital, Chengdu, China.
  • Ge RS; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou, China.
  • Xu RA; Department of Pharmacy, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Environ Toxicol ; 38(10): 2361-2376, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37357847
ABSTRACT
Bisphenol S (BPS) is a novel bisphenol A (BPA) analogue, a ubiquitous environmental pollutant that disrupts male reproductive system. Whether BPS affects Leydig cell maturation in male puberty remains unclear. Male Sprague-Dawley rats (age of 35 days) were daily gavaged to 0, 1, 10, 100, and 200 mg/kg/day from postnatal days 35-56. BPS at 1-10 mg/kg/day and higher doses markedly reduced serum testosterone and progesterone levels but it at 200 mg/kg/day significantly increased estradiol level. BPS at 100 and 200 mg/kg/day significantly elevated serum luteinizing hormone (LH) levels. BPS at 1-10 mg/kg/day and higher doses significantly reduced inhibin A and inhibin B levels. BPS at 100 and 200 mg/kg/day markedly increased CYP11A1+ Leydig cell number, but did not affect HSD11B1+ (a mature Leydig cell marker) cell number. BPS at 10 mg/kg/day and higher doses significantly downregulated the expression of Cyp11a1 and at 100 and 200 mg/kg/d significantly lowered Cyp17a1, Hsd11b1, and Nr5a1 in the testes. BPS at 100 and/or 200 mg/kg/day significantly elevated Lhb in the pituitary. BPS at 100 and 200 mg/kg/day significantly increased the phosphorylation of AKT1, AKT2, and CREB without affecting total AKT1, AKT2, and CREB levels. BPS at 1-100 µM significantly suppressed testosterone production and induced proliferation of primary immature Leydig cells after 24 h of treatment and these actions were reversed by estrogen receptor α antagonist, ICI 182780, and partially reversed by vitamin E. BPS at 0.1-10 µM significantly increased oxidative stress of Leydig cells in vitro. BPS also directly inhibited 17ß-hydroxysteroid dehydrogenase 3 activity at 10-100 µM. In conclusion, BPS causes hypergonadotropic androgen deficiency in male rats during pubertal exposure via activating ESR1 and inducing ROS in immature Leydig cells and directly inhibiting 17ß-hydroxysteroid dehydrogenase 3 activity.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Testosterona / Enzima de Desdoblamiento de la Cadena Lateral del Colesterol Límite: Animals Idioma: En Año: 2023 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Testosterona / Enzima de Desdoblamiento de la Cadena Lateral del Colesterol Límite: Animals Idioma: En Año: 2023 Tipo del documento: Article