National Institute of Animal Biotechnology, Hyderabad 50032, India; Regional Centre for Biotechnology, Faridabad, Haryana, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology, Roorkee 247667, India.
Pestic Biochem Physiol. 2024 Sep;204:106065. doi: 10.1016/j.pestbp.2024.106065. Epub 2024 Jul 31.
Organophosphate pesticides have potent endocrine disrupting effects, hence banned in many countries. However, many organophosphates like chlorpyrifos, malathion et cetera continue to be used in some countries (Wołejko et al., 2022; Wołejko et al., 2022)including India. Fodder mediated ingestion of these substances may be harmful for livestock fertility. We have investigated the effect of the widely used organophosphate pesticide chlorpyrifos (CPF) and its metabolite, 3,5,6-trichloropyridinol (TCPy) on the expression of genes essential for spermatogenesis in goat testicular tissue. The testicular Sertoli cells (Sc) regulate germ cell division and differentiation under the influence of follicle stimulating hormone (FSH) and testosterone (T). Impaired FSH and T mediated signalling in Sc can compromise spermatogenesis leading to sub-fertility/infertility. As Sc express receptors (R) for FSH and T, they are highly susceptible to the endocrine disrupting effects of pesticides affecting fertility by dysregulating the functioning of Sc. Our results indicated that exposure to different concentrations of CPF and TCPy can compromise Sc function by downregulating the expression of FSHR and AR which was associated with a concomitant decline in the expression of genes essential for germ cell division and differentiation, like KITLG, INHBB, CLDN11 and GJA1. CPF also induced a significant reduction in the activity of acetylcholinesterase in the testes and increased the total testicular antioxidant capacity. Our results suggested that CPF and its metabolite TCPy may induce reproductive toxicity by dysregulating the expression of Sc specific genes essential for spermatogenesis.
有机磷农药具有很强的内分泌干扰作用,因此在许多国家被禁用。然而,许多有机磷农药,如毒死蜱、马拉硫磷等,仍在一些国家(Wołejko 等人,2022 年;Wołejko 等人,2022 年)包括印度使用。这些物质通过饲料摄入可能对家畜的繁殖力有害。我们研究了广泛使用的有机磷农药毒死蜱(CPF)及其代谢物 3,5,6-三氯吡啶醇(TCPy)对山羊睾丸组织中精子发生所必需的基因表达的影响。睾丸支持细胞(Sc)在促卵泡激素(FSH)和睾酮(T)的影响下调节生殖细胞的分裂和分化。Sc 中 FSH 和 T 介导的信号转导受损会影响精子发生,导致生育能力下降/不育。由于 Sc 表达 FSH 和 T 的受体(R),它们对杀虫剂的内分泌干扰作用非常敏感,通过失调 Sc 的功能来影响生育能力。我们的结果表明,暴露于不同浓度的 CPF 和 TCPy 可通过下调 FSHR 和 AR 的表达来损害 Sc 的功能,这与生殖细胞分裂和分化所必需的基因的表达同时下降有关,如 KITLG、INHBB、CLDN11 和 GJA1。CPF 还导致睾丸中乙酰胆碱酯酶的活性显著降低,并增加了睾丸的总抗氧化能力。我们的结果表明,CPF 及其代谢物 TCPy 可能通过失调精子发生所必需的 Sc 特异性基因的表达来诱导生殖毒性。