Melatonin ameliorates Pb-induced mitochondrial homeostasis and ovarian damage through regulating the p38 signaling pathway

作者：Zhuo-Nan Yang, Xin Du, An Wang, Yuhang Zhao, Yun-he Xia, Ling-ge Shi, Si-Min Ding, Xinyu Yue, Fen Xing, Dongmei Ji, Dan Liang, Zhengbao Zha, Chunmei Liang, Yunxia Cao, Ya-jing Liu · 发表于：Ecotoxicology and Environmental Safety · 年份：2025 · DOI：10.1016/j.ecoenv.2025.117937 · 被引用次数：12 · 研究领域：Birth, Development, and Health、Heavy Metal Exposure and Toxicity、Magnesium in Health and Disease

Lead (Pb), a widespread metallic pollutant in the environment, has been found to have detrimental effects on the female reproduction system. Recently, our group discovered a significant correlation between toxic metals and reproductive endocrine diseases. However, there is limited research on the relationship between blood concentration of Pb and the risk of diminished ovarian reserve function (DOR). Melatonin (MT), as a unique antioxidant, has been shown to reduce Pb toxicity both in vivo and in vitro，but the role of MT on follicle development in Pb-exposed female C57BL6 mice, and the underlying mechanisms, have not been clearly identified. In this study, blood Pb level was detected in the DOR patients, and a significant elevation in Pb levels was observed compared to the control group. Subsequently, we investigated the impact of lead acetate trihydrate (0.2 %), an endocrine disruptor of heavy metals, on follicle development in mice. We observed abnormal follicle development induced by lead acetate trihydrate without concurrent follicular apoptosis or excessive autophagy. Furthermore, we found that co-treatment with MT (30 mg/kg) rescued Pb-induced abnormal follicle development. Anti-Müllerian hormone (AMH) is a commonly utilized marker to evaluate ovarian reserve function. Our observation revealed that MT treatment effectively reversed the decrease in AMH levels induced by Pb. Importantly, our results revealed that MT not only protected against the Pb-induced increase of nu...