Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.
Zhongnan Hospital of Wuhan University, Wuhan, China.
Toxicol Ind Health. 2023 Sep;39(9):481-490. doi: 10.1177/07482337221140221. Epub 2023 Jul 6.
Methomyl is a carbamate insecticide with confirmed testicular toxicity. This study intended to observe the effect of methomyl on testicular cells and the protective effect of folic acid through in experiments. The GC-1 spermatogonia, TM4 Sertoli cells, and TM3 Leydig cells were treated with methomyl (0, 250, 500, and 1000 μM) with or without folic acid (0, 10, 100, and 1000 nM) for 24 h. It was found that methomyl increased cytotoxicity to testicular cells in a dose-dependent manner. In spermatogonia, methomyl significantly inhibited the expression of proliferation genes Ki67 and PCNA at 1000 μM, and increased the expression of apoptosis genes Caspase3 and Bax at each dose. In Sertoli cells, methomyl dose-dependently inhibited the expression of blood-testis barrier function genes TJP1, Cx43, and N-cadherin, but did not affect Occludin and E-cadherin. In Leydig cells, methomyl inhibited the expression of steroid synthase P450scc, StAR, Hsd3b1 and down-regulated the level of testosterone, but did not affect Cyp17a1 and Hsd17b1. Further, folic acid could basically reduce the damage caused by methomyl. This study provided new insights into the toxicity of methomyl and the protective effect of folic acid.
灭多威是一种氨基甲酸酯类杀虫剂,已被证实具有睾丸毒性。本研究旨在通过实验观察灭多威对睾丸细胞的影响以及叶酸的保护作用。将 GC-1 精原细胞、TM4 支持细胞和 TM3 间质细胞分别用灭多威(0、250、500 和 1000 μM)和/或叶酸(0、10、100 和 1000 nM)处理 24 小时。结果发现,灭多威对睾丸细胞的细胞毒性呈剂量依赖性增加。在精原细胞中,1000 μM 灭多威显著抑制增殖基因 Ki67 和 PCNA 的表达,各剂量下凋亡基因 Caspase3 和 Bax 的表达增加。在支持细胞中,灭多威剂量依赖性地抑制血睾屏障功能基因 TJP1、Cx43 和 N-cadherin 的表达,但不影响 Occludin 和 E-cadherin。在间质细胞中,灭多威抑制类固醇合成酶 P450scc、StAR、Hsd3b1 的表达,并降低睾酮水平,但不影响 Cyp17a1 和 Hsd17b1。此外,叶酸基本可以减轻灭多威造成的损伤。本研究为灭多威的毒性和叶酸的保护作用提供了新的见解。