Melatonin alleviates the deterioration of oocytes and hormonal disorders from mice subjected to glyphosate

摘要

Glyphosate (Gly) is the herbicide widely used in agricultural fields and landscaping. Mammalian exposure to glyphosate could cause neurotoxicity, blood, liver, kidney, endocrine, reproductive, genetic and other toxic effects. Melatonin (MT) is a neuroendocrine hormone secreted mainly by the pineal gland. It is unknown whether MT can improve reproductive defects and hormonal disorders in mice exposed to Gly. In this study, mice were exposed to 250 and 500 mg/kg Gly by intragastric administered and 15 mg/kg MT was treated via intraperitoneal injection for 7 days. Our results shown that the weight gain of mice, the ovarian coefficient and the ATP content in the ovaries were decreased significantly. Gly-treated oocytes showed that the first polar body extrusion failed, the level of oxidative stress increased, and the mitochondrial membrane potential (MMP) decreased. Subsequently, our results showed that increased expression level of BAX protein, reduced expression of BCL-2 protein, ATG12 and LC3 protein expression increased in ovaries after Gly treatment. At the same time, Gly exposure led to abnormal expression of Hypothalamic-Pituitary-Thyroid (HPT) axis-related genes and disrupted hormone homeostasis. After the injection of 15 mg/kg MT, the oocytes showed decreased oxidative stress level, increased mitochondrial membrane potential, incremental ATP content in the ovaries and the hormone levels were approached to the control group. Thus, our results demonstrated that melatonin can improve oocyte quality and maintain hormone homeostasis in mice exposed to glyphosate.