Different effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on sex hormone levels, metabolic profile and oxidative stress in adult mice testes.

In the environment, endosulfan persists in forms of two isomers (α and β) and a toxic metabolite, endosulfan sulfate. The toxicity of endosulfan on various mammalian tissues has been investigated, but whether the different isomers and metabolites of endosulfans affect mammalian reproductive function remains unclear. This study is aimed to elucidate the different toxicological effects of α-endosulfan, β-endosulfan, and endosulfan sulfate on adult mice testes. We found that the three endosulfans (α endosulfan, β endosulfan and endosulfan sulfate) altered serum sex steroid hormone levels, and changed expression of steroidogenesis genes. By comparing results of H-NMR and LC-MS/MS metabolomics between samples treated with different endosulfans, we found that endosulfans changed levels of metabolites involved in energy metabolism and oxidative stress, and these were associated with the imbalance of sex sterol hormone synthesis. Moreover, endosulfan isomers and sulfate metabolite treatment disrupted the mice testicular antioxidant systems and caused an increase in lipid peroxidation. Interestingly, the three endosulfans tested in this study each yielded different effects on serum sex hormone levels and testicular metabolic profiles in the adult mice. Beta-endosulfan exposure caused the strongest disturbance in the testes compared to the other endosulfans, with significantly higher testosterone levels and more pronounced changes to endogenous metabolites. Taken together, we identified the different effects of endosulfans on the testis by exposing mice to α endosulfan, β endosulfan and endosulfan sulfate, and we found that changes in sex sterol hormone levels induced by treatment with endosulfans were correlated to changes in endogenous metabolites. These findings provide new insight into mechanism of endosulfan-induced testicular toxicity.