Abstract：
Di(2-ethylhexyl) phthalate (DEHP) is a widely recognized environmental endocrine disruptor that potentially impacts female reproductive function, although the specific mechanisms leading to such impairment remain unclear. A growing body of research has revealed that the endoplasmic reticulum and mitochondrial function significantly influence oocyte quality. The structure of mitochondria-associated endoplasmic reticulum membranes (MAMs) is crucial for facilitating the exchange of Ca2+, lipids, and metabolites. This study aimed to investigate the alterations in the composition and function of MAMs after DEHP exposure and to elucidate the underlying mechanisms of ovarian toxicity. The female mice were exposed to DEHP at doses of 5 and 500 mg/kg/day for one month. The results revealed that DEHP exposure led to reduced serum anti-Müllerian hormone levels and increased atretic follicles in mice. DEHP induced endoplasmic reticulum stress and disrupted calcium homeostasis in oocytes. Furthermore, DEHP impaired the mitochondrial function of oocytes and reduced their membrane potential, and promoting apoptosis. Similar results were observed in human granulosa cells after exposure to mono-(2-ethylhexyl) phthalate (MEHP, metabolites of DEHP) in vitro. Proteomic analysis and transmission electron microscopy revealed modifications in the functional proteins and structure of the MAMs, and the suppression of oxidative phosphorylation pathways. The findings of this investigation provide a new perspective on the mechanism underlying the reproductive toxicity of DEHP in females.
摘要：
邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种广泛认可的环境内分泌干扰物，可能影响女性生殖功能，尽管导致此类损害的具体机制尚不清楚.越来越多的研究表明，内质网和线粒体功能显着影响卵母细胞的质量。线粒体相关的内质网膜（MAMs）的结构对于促进Ca2交换至关重要，脂质，和代谢物。本研究旨在研究DEHP暴露后MAMs的组成和功能的变化，并阐明卵巢毒性的潜在机制。雌性小鼠以5和500mg/kg/天的剂量暴露于DEHP一个月。结果表明，DEHP暴露会导致小鼠血清抗苗勒管激素水平降低，并增加小鼠的闭锁卵泡。DEHP诱导内质网应激和破坏卵母细胞钙稳态。此外，DEHP损害卵母细胞的线粒体功能并降低其膜电位，促进细胞凋亡。在暴露于邻苯二甲酸单（2-乙基己基）酯（MEHP，DEHP的代谢物)。蛋白质组学分析和透射电子显微镜显示了MAM的功能蛋白和结构的修饰，以及氧化磷酸化途径的抑制。这项研究的结果为DEHP对女性生殖毒性的潜在机制提供了新的视角。
