Perfluorododecanoic Acid Blocks Rat Leydig Cell Development during Prepuberty
Perfluorododecanoic Acid Blocks Rat Leydig Cell Development during Prepuberty
复制标题
全氟十二烷酸可阻断青春期前大鼠 Leydig 细胞的发育
DOI：
10.1021/acs.chemrestox.8b00241
复制
发表时间：
2019-01-01
影响因子：
4.1
通讯作者：
Ge, Ren-Shan
中科院分区：
文献类型：
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作者：
Chen, Yong;Li, Huitao;Ge, Ren-Shan
全氟十二烷酸（PFDoA）已被用作表面活性剂，可能具有生殖毒性。然而，PFDoA是否影响青春期前睾丸间质细胞的发育仍不清楚。在本研究中，21日龄雄性Sprague-Dawley大鼠从出生后第21天至第35天灌胃0、5或10 mg/kg PFDoA。在5和10 mg/kg剂量下，PFDoA降低了睾酮、促黄体生成素和促卵泡激素的血清浓度，而不影响Leydig细胞数量和增殖。然而，PFDoA下调Leydig细胞基因（Lhcgr、Scarb 1、星星、Cyp 11 a1、Cyp 17 a1和Hsd 11 b1）或其蛋白的表达。PFDoA剂量依赖性地降低SIRT 1和PGC-1 α水平。PFDoA不影响AMPK和AKT 2水平，但降低其磷酸化。我们还用PFDoA处理了从青春期前大鼠睾丸中纯化的原代前体Leydig细胞24 h。它在体外降低了Leydig祖细胞的存活率和线粒体膜电位，但在10 μ M时刺激了细胞内活性氧的产生并诱导Leydig细胞凋亡。总之，PFDoA可能通过靶向AMPK/SIRT 1/PGC-1 α和AKT 2信号通路阻断大鼠青春期前Leydig细胞发育。
Perfluorododecanoic acid (PFDoA) has been used as a surfactant and may have reproductive toxicity. However, whether PFDoA influences Leydig cell development during prepuberty remains unknown. In the present study, 21-day-old male Sprague-Dawley rats were gavaged 0, 5, or 10 mg/kg PFDoA from postnatal day 21 to 35. PFDoA decreased the serum concentrations of testosterone, luteinizing hormone, and follicle-stimulating hormone at doses of 5 and 10 mg/kg without influencing Leydig cell number and proliferation. However, PFDoA down-regulated the expression of Leydig cell genes (Lhcgr, Scarb1, Star, Cyp11a1, Cyp17a1, and Hsd11b1) or their proteins. PFDoA dose-dependently reduced SIRT1 and PGC-1 alpha levels. PFDoA did not affect AMPK and AKT2 levels but decreased their phosphorylation. We also treated primary progenitor Leydig cells purified from prepubertal rat testes with PFDoA for 24 h. It in vitro lowered viability and decreased mitochondrial membrane potential of progenitor Leydig cells, but it stimulated the generation of the intracellular reactive oxygen species and induced Leydig cell apoptosis at 10 mu M. In conclusion, PFDoA blocks rat Leydig cell development during the prepubertal period possibly via targeting AMPK/SIRT1/PGC-1 alpha and AKT2 signaling pathways.