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  2. Perfluoroundecanoic acid inhibits Leydig cell development in pubertal male rats via inducing oxidative stress and autophagy

Perfluoroundecanoic acid inhibits Leydig cell development in pubertal male rats via inducing oxidative stress and autophagy

  • Toxicol Appl Pharmacol. 2021 Mar 15:415:115440. doi: 10.1016/j.taap.2021.115440.
Haoni Yan 1 Changchang Li 1 Cheng Zou 2 Xiu Xin 1 Xiaoheng Li 1 Huitao Li 2 Yang Li 1 Zengqiang Li 1 Yiyan Wang 1 Haolin Chen 3 Ren-Shan Ge 4
Affiliations

Affiliations

  • 1 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 3 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: chenhaolin@wmu.edu.cn.
  • 4 Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: r_ge@yahoo.com.
Abstract

Perfluoroundecanoic acid (PFUnA) is one of long-chain perfluoroalkyl carboxylic acids. However, the effect of PFUnA on pubertal development of Leydig cells remains unclear. The goal of this study was to investigate the effect of PFUnA on Leydig cell development in pubertal male rats. We orally dosed male Sprague-Dawley rats (age 35 days) with PFUnA at doses of 0, 1, 5, and 10 mg/kg/day from postnatal day (PND) 35 to PND 56. Serum testosterone and luteinizing hormone levels were remarkably reduced by PFUnA at ≥1 mg/kg while serum follicle-stimulating hormone levels were lowered at 5 and 10 mg/kg. PFUnA down-regulated the expression of Lhcgr, Scarb1, Star, Cyp11a1, Hsd3b1, CYP17A1, Hsd17b3, Hsd11b1, Insl3, Nr5a1, Fshr, Dhh, Sod1, and Sod2 and their proteins in the testis and the expression of Lhb and Fshb in the pituitary. PFUnA reduced Leydig cell number at 5 and 10 mg/kg. PFUnA induced oxidative stress and increased Autophagy. These may result from the inhibition of phosphorylation of mTOR, Akt1, Akt2, and ERK1/2 in the testis. In conclusion, PFUnA exhibits inhibitory effects on pubertal Leydig cell development possibly via inducing oxidative stress and increasing Autophagy.

Keywords

Leydig cells; Perfluoroundecanoic acid; Pubertal development; Steroidogenesis; Tstosterone.

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