Yan Haoni, Li Changchang, Zou Cheng, Xin Xiu, Li Xiaoheng, Li Huitao, Li Yang, Li Zengqiang, Wang Yiyan, Chen Haolin, Ge Ren-Shan
Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Toxicol Appl Pharmacol. 2021 Mar 15;415:115440. doi: 10.1016/j.taap.2021.115440. Epub 2021 Feb 5.
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.
全氟十一烷酸（PFUnA）是长链全氟烷基羧酸之一。然而，PFUnA对睾丸间质细胞青春期发育的影响仍不清楚。本研究的目的是探讨PFUnA对青春期雄性大鼠睾丸间质细胞发育的影响。从出生后第35天（PND 35）至PND 56，我们以0、1、5和10 mg/kg/天的剂量对雄性Sprague-Dawley大鼠（35日龄）口服PFUnA。当剂量≥1 mg/kg时，PFUnA显著降低血清睾酮和黄体生成素水平，而在5和10 mg/kg时血清促卵泡激素水平降低。PFUnA下调睾丸中Lhcgr、Scarb1、Star、Cyp11a1、Hsd3b1、Cyp17a1、Hsd17b3、Hsd11b1、Insl3、Nr5a1、Fshr、Dhh、Sod1和Sod2及其蛋白的表达以及垂体中Lhb和Fshb的表达。PFUnA在5和10 mg/kg时减少睾丸间质细胞数量。PFUnA诱导氧化应激并增加自噬。这可能是由于睾丸中mTOR、AKT1、AKT2和ERK1/2磷酸化受到抑制所致。总之，PFUnA可能通过诱导氧化应激和增加自噬对青春期睾丸间质细胞发育产生抑制作用。
