Perfluorotridecanoic acid (PFTrDA) is a long‐chain perfluoroalkyl substance, and its effect on the differentiation of fetal Leydig cells remains unclear. The objective of this study is to explore the effect of in utero PFTrDA exposure on the differentiation of fetal Leydig cells and investigate its underlying mechanisms. Pregnant Sprague–Dawley female rats were daily administered by gavage of PFTrDA at doses of 0, 1, 5, and 10 mg/kg from gestational day 14 to 21. PFTrDA had no effect on the body weight of dams, but significantly reduced the body weight and anogenital distance of male pups at birth at a dose of 10 mg/kg. PFTrDA significantly decreased serum testosterone levels as low as 1 mg/kg. PFTrDA did not affect fetal Leydig cell number, but promoted abnormal aggregation of fetal Leydig cells at doses of 5 and 10 mg/kg. PFTrDA down‐regulated the expression of Insl3, Lhcgr, Scarb1, Star, Hsd3b1, Cyp17a1, Nr5a1, and Dhh as well as their proteins. PFTrDA lowered the levels of antioxidants (SOD1, CAT, and GPX1), induced autophagy as shown by increased levels of LC3II and beclin1, and reduced the phosphorylation of mTOR. In conclusion, PFTrDA inhibits the differentiation of fetal Leydig cells in male pups after in utero exposure mainly through increasing oxidative stress and inducing autophagy.

中文翻译：

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全氟十三烷酸通过增加氧化应激和自噬抑制大鼠子宫内暴露后胎儿Leydig细胞的分化

全氟十三烷酸（PFTrDA）是长链全氟烷基物质，其对胎儿Leydig细胞分化的影响尚不清楚。这项研究的目的是探讨宫内PFTrDA暴露对胎儿Leydig细胞分化的影响并研究其潜在机制。从妊娠第14天到第21天，每天以0、1、5和10 mg / kg的剂量灌胃PFTrDA，对怀孕的Sprague-Dawley雌性大鼠进行每日给药。PFTrDA对大坝的体重没有影响，但会显着减轻身体的重量剂量为10 mg / kg时，雄性幼崽的体重和肛门生殖器距离。PFTrDA显着降低血清睾丸激素水平，低至1 mg / kg。PFTrDA不会影响胎儿Leydig细胞的数量，但会以5和10 mg / kg的剂量促进胎儿Leydig细胞的异常聚集。Insl3，Lhcgr，Scarb1，Star，Hsd3b1，Cyp17a1，Nr5a1和Dhh以及它们的蛋白质。PFTrDA降低了抗氧化剂（SOD1，CAT和GPX1）的水平，诱导了自噬，如LC3II和beclin1的水平升高，以及mTOR的磷酸化降低。总之，PFTrDA抑制子宫内暴露后雄性幼崽胎儿Leydig细胞的分化，主要是通过增加氧化应激和诱导自噬来实现的。