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  3. Bisphenol F blocks Leydig cell maturation and steroidogenesis in pubertal male rats through suppressing androgen receptor signaling and activating G-protein coupled estrogen receptor 1 (GPER1) signaling

Bisphenol F blocks Leydig cell maturation and steroidogenesis in pubertal male rats through suppressing androgen receptor signaling and activating G-protein coupled estrogen receptor 1 (GPER1) signaling

  • Food Chem Toxicol. 2022 Sep;167:113268. doi: 10.1016/j.fct.2022.113268.
Huitao Li 1,  Jingjing Li 1,  Lei Shi 2,  Yang Zhu 3,  Fuhong Tian 3,  Mengna Shi 3,  Qiyao Li 3,  Ren-Shan Ge 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's, Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China.
  • 2 Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China.
  • 3 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's, Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China.
  • 4 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's, Hospital, Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan West Road, Wenzhou, Zhejiang, 325027, China. Electronic address: r_ge@yahoo.com.
PMID: 35803362 DOI: 10.1016/j.fct.2022.113268
Abstract

Bisphenol F (BPF) is a new analog of bisphenol A (BPA). BPA has deleterious effects on the male reproductive system, but the effect of BPF has not been studied in detail. In this study we focus on the effect of BPF on Leydig cell maturation. Male Sprague-Dawley rats were gavaged with 0, 1, 10, or 100 mg/kg BPF from postnatal days 35-56. BPF significantly reduced serum testosterone levels and sperm count in cauda epididymis at dose ≥1 mg/kg. It significantly down-regulated the expression of steroidogenic Enzymes, while increasing FSHR and SOX9 levels at 10 and 100 mg/kg. Further studies showed that BPF reduced NR3C4 expression in Leydig and Sertoli cells without affecting its levels in peritubular myoid cells. BPF markedly increased GPER1 in Leydig cells at 100 mg/kg, and it significantly reduced SIRT1 and PGC1α levels in the testes at 100 mg/kg. BPF significantly inhibited testosterone production by immature Leydig cells at 50 μM after 24 h of treatment, which was completely reversed by NR3C4 agonist 7α-methyl-19-nortestosterone and partially reversed by GPER1 antagonist G15 not by ESR1 antagonist ICI 182,780. In conclusion, BPF negatively affects Leydig cell maturation in pubertal male rats through NR3C4 antagonism and GPER1 agonism.

Keywords

Androgen receptor; Bisphenol F; G-protein coupled estrogen receptor 1; Leydig cell maturation; Steroidogenesis.

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