College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Pestic Biochem Physiol. 2024 Aug;203:106010. doi: 10.1016/j.pestbp.2024.106010. Epub 2024 Jul 2.
Thiram, a prevalent dithiocarbamate insecticide in agriculture, is widely employed as a crop insecticide and preservative. Chronic exposure to thiram has been linked to various irreversible damages, including tibial cartilage dysplasia, erythrocytotoxicity, renal issues, and immune system compromise. Limited research exists on its effects on reproductive organs. This study investigated the reproductive toxicology in mouse testes exposure to varying concentrations (0, 30, 60, and 120 mg/kg) of thiram. Our study uncovered a series of adverse effects in mice subjected to thiram exposure, including emaciation, stunted growth, decreased water intake, and postponed testicular maturation. Biochemical analysis in thiram-exposed mice showed elevated levels of LDH and AST, while ALP, TG, ALT, and urea were decreased. Histologically, thiram disrupted the testis' microarchitecture and compromised its barrier function by widening the gap between spermatogenic cells and promoting fibrosis. The expression of pro-apoptotic genes (Bax, APAF1, Cytc, and Caspase-3) was downregulated, whereas Bcl-2 expression increased in thiram-treated mice compared to controls. Conversely, the expression of Atg5 was upregulated, and mTOR and p62 expression decreased, with a trend towards lower LC3b levels. Thiram also disrupted the blood-testis barrier, significantly reducing the mRNA expression of zona occludens-1 (ZO-1) and occludin. In conclusion, chronic exposure to high thiram concentrations (120 mg/kg) caused testicular tissue damage, affecting the blood-testis barrier and modulating apoptosis and autophagy through the Bcl-2/Bax and mTOR/Atg5/p62 pathways. This study contributes to understanding the molecular basis of thiram-induced reproductive toxicity and underscores the need for further research and precautions for those chronically exposed to thiram and its environmental residuals.
代森锰锌是一种普遍存在的二硫代氨基甲酸酯类农药，在农业中被广泛用作作物杀虫剂和防腐剂。慢性代森锰锌暴露与多种不可逆损害有关，包括胫骨软骨发育不良、红细胞毒性、肾脏问题和免疫系统受损。关于其对生殖器官的影响的研究有限。本研究调查了不同浓度（0、30、60 和 120mg/kg）代森锰锌暴露于小鼠睾丸的生殖毒理学。我们的研究发现，暴露于代森锰锌的小鼠出现了一系列不良影响，包括消瘦、生长迟缓、饮水量减少和睾丸成熟延迟。在暴露于代森锰锌的小鼠中进行的生化分析显示，LDH 和 AST 水平升高，而 ALP、TG、ALT 和尿素降低。组织学分析显示，代森锰锌破坏了睾丸的微结构，通过扩大生精细胞之间的间隙并促进纤维化来损害其屏障功能。与对照组相比，促凋亡基因（Bax、APAF1、Cytc 和 Caspase-3）的表达下调，而 Bcl-2 的表达上调。相反，Atg5 的表达上调，mTOR 和 p62 的表达下调，LC3b 水平呈下降趋势。代森锰锌还破坏了血睾屏障，显著降低了 zona occludens-1（ZO-1）和occludin 的 mRNA 表达。总之，慢性暴露于高浓度代森锰锌（120mg/kg）导致睾丸组织损伤，影响血睾屏障，并通过 Bcl-2/Bax 和 mTOR/Atg5/p62 途径调节细胞凋亡和自噬。本研究有助于理解代森锰锌诱导生殖毒性的分子基础，并强调需要进一步研究和防范那些长期暴露于代森锰锌及其环境残留的人群。
