Melatonin mitigates PNMC-induced disruption of spindle assembly and mitochondrial function in mouse Oocytes

• Published in: Ecotoxicology and environmental safety Vol. 282; p. 116703
• Main Authors: Ma, Cong, Xu, Yan, Zhang, Xueke, Shi, Xuejiao, Zhang, Yingying, Luo, Meijie, Wu, Caiyun, Ding, Zhiming, Xiang, Huifen, Cao, Yunxia
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2024; Elsevier
• Subjects: Melatonin; Mitochondria; Oocyte meiosis; PNMC; PNMC; Mitochondria; Melatonin; Oocyte meiosis
• ISSN: 0147-6513; 1090-2414; 1090-2414
• DOI: 10.1016/j.ecoenv.2024.116703

3-methyl-4-nitrophenol (PNMC), a degradation product of organophosphorus insecticides and a byproduct of fuel combustion, exerting endocrine-disrupting effects. However, its impact on the meiotic process of oocytes remains unclear. In the present study, we investigated the effects of PNMC on meiotic maturation of mouse oocytes in vitro and related mechanisms. Morphologically, PNMC-exposure affected germinal vesicle breakdown (GVBD) and polar body extrusion (PBE) in mouse oocytes. Proteomic analysis suggested that PNMC-exposure altered oocyte protein expression that are associated with cytoskeleton, mitochondrial function and oxidative stress. Further studies demonstrated that PNMC-exposure disrupted spindle assembly and chromosome alignment, caused sustained activation of spindle assembly checkpoint (SAC), and arrested meiosis in oocytes. Specifically, PNMC-exposure interfered with the function of microtubule organizing centers (MTOCs) by significantly reducing phosphorylated mitogen activated protein kinase (p-MAPK) expression and disrupting the localization of Pericentrin and p-Aurora A, leading to spindle assembly failure. Besides, PNMC-exposure also increased α-tubulin acetylation, decreased microtubule stability. Moreover, PNMC-exposure impaired mitochondrial function, evidenced by abnormal mitochondrial distribution, decreased mitochondrial membrane potential and ATP levels, release of Cytochrome C into the cytoplasm, and elevated ROS levels. As a result, exposure to PNMC caused DNA damage and early apoptosis in oocytes. Fortunately, melatonin was able to promote oocyte maturation by removing the excessive ROS and enhancing mitochondrial function. These results highlight the adverse effects of PNMC on meiotic maturation, and underscore the protective role of melatonin against PNMC-induced damage. [Display omitted] •PNMC exposure hinders the process of oocyte meiotic resumption and the extrusion of the first polar body.•PNMC exposure diminishes the levels of p-MAPK, resulting in the disruption of spindle assembly and chromosome alignment.•PNMC exposure diminishes mitochondrial membrane potential, leading to inadequate ATP production.•PNMC exposure disrupts the homeostasis of ROS metabolism within mitochondria, causing oxidative stress and early apoptosis.•Melatonin augments the antioxidant defense system within mitochondria, thereby safeguarding oocytes against the impairment of meiotic maturation induced by PNMC exposure.