Glyphosate (GLY) is a widely used herbicide that has been revealed to inhibit testosterone synthesis in humans and animals. Melatonin (MET) is an endogenous hormone that has been demonstrated to promote mammalian testosterone synthesis via protecting mitochondrial function. However, it remains unclear whether MET targets mitochondria to alleviate GLY-inhibited testosterone synthesis in avian. In this study, an avian model using 7-day-old rooster upon chronic exposure to GLY with the treatment of MET was designed to clarify this issue. Data first showed that GLY-induced testicular Leydig cell damage, structural damage of the seminiferous tubule, and sperm quality decrease were mitigated by MET. Transcriptomic analyses of the testicular tissues revealed the potentially critical role of mitophagy and steroid hormone biosynthesis in the process of MET counteracting GLY-induced testicular damage. Also, validation data demonstrated that the inhibition of testosterone synthesis due to GLY-induced mitochondrial dynamic imbalance and concomitant Parkin-dependent mitophagy activation is alleviated by MET. Moreover, GLY-induced oxidative stress in serum and testicular tissue were significantly reversed by MET. In summary, these findings demonstrate that MET effectively ameliorates GLY-inhibited testosterone synthesis by inhibiting mitophagy activation, which provides a promising remedy for the application of MET as a potential therapeutic agent to antagonize reproductive toxicity induced by GLY and similar contaminants.

中文翻译：

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褪黑素通过靶向公鸡线粒体功能减轻草甘膦诱导的睾酮合成抑制

草甘膦 (GLY) 是一种广泛使用的除草剂，已被证明可以抑制人类和动物的睾酮合成。褪黑激素（MET）是一种内源性激素，已被证明可以通过保护线粒体功能来促进哺乳动物睾酮的合成。然而，目前尚不清楚 MET 是否靶向线粒体来减轻禽类中 GLY 抑制的睾酮合成。在这项研究中，设计了一个使用长期暴露于 GLY 并接受 MET 治疗的 7 日龄公鸡的禽类模型来澄清这个问题。数据首先表明，MET 可减轻 GLY 引起的睾丸 Leydig 细胞损伤、曲细精管结构损伤和精子质量下降。睾丸组织的转录组分析揭示了线粒体自噬和类固醇激素生物合成在 MET 抵抗 GLY 诱导的睾丸损伤过程中的潜在关键作用。此外，验证数据表明，由于 GLY 诱导的线粒体动态失衡和伴随的 Parkin 依赖性线粒体自噬激活而导致的睾酮合成抑制可通过 MET 得到缓解。此外，MET 显着逆转 GLY 诱导的血清和睾丸组织氧化应激。总之，这些发现表明，MET 通过抑制线粒体自噬激活，有效改善 GLY 抑制的睾酮合成，这为 MET 作为潜在治疗剂拮抗 GLY 和类似污染物引起的生殖毒性提供了一种有前途的补救措施。