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However, the exact mechanism by which methylmercury chloride (MMC) affects this process remains elusive. The present study found that MMC administration triggered meiotic failure in oocytes by disrupting cumulus cell expansion, leading to compromised spindle apparatus and altered chromosomal architecture, which are crucial for oocyte development. This disruption is characterized by abnormal microtubule organization and defective chromosome alignment. Additionally, MMC exposure caused oxidative stress-induced apoptosis due to mitochondrial dysfunction, as indicated by decreased mitochondrial membrane potential, mitochondrial content, mitochondrial DNA copy number, and adenosine triphosphate levels. Proteomic analysis identified 97 differentially expressed proteins, including P62, an autophagy marker. Our results confirmed that MMC induced autophagy, particularly through the hyperactivation of the mitochondrial autophagy to remove damaged and normal mitochondria. The mitochondrial reactive oxygen species (ROS) scavenger Mito-TEMPO alleviated oxidative stress and mitochondrial autophagy levels, suggesting that mitochondrial ROS initiates this autophagic response. Notably, MMC activates mitochondrial autophagy via the monophosphate-activated protein kinase (AMPK)\/mammalian target of rapamycin (mTOR) signal pathway due to mitochondrial dysfunction. In vivo studies in mice revealed that MMC exposure decreased reproductive performance, attributed to excessive mitochondrial autophagy leading to reduced oocyte quality. Overall, these findings demonstrate that MMC exposure impairs oocyte maturation via the hyperactivation of mitochondrial autophagy induced by mitochondrial dysfunction.<\/jats:p>","DOI":"10.3390\/ijms26083603","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T05:38:26Z","timestamp":1744349906000},"page":"3603","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Methylmercury Chloride Exposure Affects Oocyte Maturation Through AMPK\/mTOR-Mediated Mitochondrial Autophagy"],"prefix":"10.3390","volume":"26","author":[{"given":"Shengkui","family":"Hou","sequence":"first","affiliation":[{"name":"Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130117, China"},{"name":"Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Ding","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130117, China"},{"name":"Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction Technology, Jilin Agricultural University, Changchun 130117, China"},{"name":"Jilin Provincial Key Laboratory of Beef Cattle Germplasm Resources Conservation and Utilization, Jilin Agricultural University, Changchun 130117, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of the Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130117, China"},{"name":"Jilin Provincial International Joint Research Center of Animal Breeding and Reproduction 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