Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Reproductive Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, 123 Tianfeixiang, Mochou Road, Nanjing 210004, Jiangsu, China.
Department of Gynecology and Obstetrics, the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Toxicol Appl Pharmacol. 2021 Dec 15;433:115777. doi: 10.1016/j.taap.2021.115777. Epub 2021 Nov 2.
Perfluorotetradecanoic acid (PFTeDA) is one of perfluoroalkyl substances widely found in the environment. PFTeDA may cause the dysfunction of male reproductive system. However, whether PFTeDA affects the regeneration of Leydig cells remains unclear. The objective of this study was to examine the effects of short-term exposure of PFTeDA on the late-stage maturation of Leydig cells. Fifty-four adult Sprague-Dawley male rats were daily gavaged with PFTeDA (0, 10, or 20 mg/kg body weight) for 10 days, and then were injected intraperitoneally with ethylene dimethane sulfonate (EDS, 75 mg/kg body weight/once) to ablate Leydig cells to induce their regeneration. On day 21 (early stage) and 56 (late stage) after EDS, hormone levels, gene expression, and protein levels were measured. PFTeDA did not affect the early stage of Leydig cell regeneration, because it had no effect on serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels, Leydig cell number, and its gene and protein expression. PFTeDA significantly reduced serum testosterone level and down-regulated the expression of Leydig cell genes (Cyp11a1, Hsd3b1, Cyp17a1, Hsd17b3, Hsd11b1, and Insl3) and their proteins (CYP11A1, HSD3B1, CYP17A1, HSD17B3, and INSL3), decreased the phosphorylation of AKT1 and ERK1/2, as well as lowered sperm count in the epididymis at 20 mg/kg. In conclusion, short-term exposure to PFTeDA blocks the late-stage maturation of Leydig cells.
全氟十四酸（PFTeDA）是环境中广泛存在的全氟烷基物质之一。PFTeDA 可能导致男性生殖系统功能障碍。然而，PFTeDA 是否影响莱迪希细胞的再生尚不清楚。本研究旨在研究 PFTeDA 短期暴露对莱迪希细胞晚期成熟的影响。54 只成年 Sprague-Dawley 雄性大鼠每天经口灌胃 PFTeDA（0、10 或 20mg/kg 体重）10 天，然后腹腔注射乙二磺酸二乙酯（EDS，75mg/kg 体重/次）以消融莱迪希细胞诱导其再生。在 EDS 后第 21 天（早期）和 56 天（晚期）测量激素水平、基因表达和蛋白水平。PFTeDA 对莱迪希细胞再生的早期阶段没有影响，因为它对血清睾酮、促黄体生成素和卵泡刺激素水平、莱迪希细胞数量及其基因和蛋白表达没有影响。PFTeDA 显著降低了血清睾酮水平，并下调了莱迪希细胞基因（Cyp11a1、Hsd3b1、Cyp17a1、Hsd17b3、Hsd11b1 和 Insl3）和其蛋白（CYP11A1、HSD3B1、CYP17A1、HSD17B3 和 INSL3）的表达，降低了 AKT1 和 ERK1/2 的磷酸化水平，以及附睾中精子计数在 20mg/kg 时下降。总之，短期暴露于 PFTeDA 会阻断莱迪希细胞的晚期成熟。
