Hubei Key Laboratory of Genetic Regulation and Integrative Biology, School of Life Sciences, Central China Normal University, Wuhan, Hubei 430079, China.
Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China.
Toxicology. 2024 Dec;509:153952. doi: 10.1016/j.tox.2024.153952. Epub 2024 Sep 10.
Globally, approximately 6-20 % of women who are of reproductive age suffer from polycystic ovary syndrome (PCOS), with environmental factors believed to be significant contributors. Di-2-ethylhexyl phthalate (DEHP) is known to be an endocrine disruptor, and is also suspected of being associated with the occurrence of PCOS, but in vivo studies to verify this association are lacking. In this study, female SD rats were exposed to DEHP at levels of 0.1, 1.0, and 10 mg/kg/d, which are comparable to daily human exposure, to explore its potential role in the development of PCOS. The findings indicated that DEHP exposure reduced ovarian and uterine coefficients, decreased accumulation of primordial follicles, increased the prevalence of atretic and cystic follicles and fibrosis in ovarian tissues, altered serum hormone levels, elevated blood glucose levels and insulin resistance, disrupted the endocrine system and resulted in significant oxidative damage in the ovarian tissues. These results imply that DEHP exposure may cause lesions resembling PCOS to develop. By analyzing the differential expression of the proteome, and using GO and KEGG enrichment analyses, we found they were mainly enriched in the metabolic pathway and in the PPAR signaling pathway. We confirmed that activation of the PPARγ signaling pathway caused by DEHP exposure, is related to the emergence of PCOS-like lesions. This research provides direct in vivo experimental evidence for the association between DEHP exposure and PCOS.
全球大约有 6-20%的育龄期女性患有多囊卵巢综合征（PCOS），环境因素被认为是其重要的致病因素。邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种内分泌干扰物，也被怀疑与 PCOS 的发生有关，但缺乏体内研究来验证这种关联。在这项研究中，雌性 SD 大鼠暴露于 DEHP 的剂量分别为 0.1、1.0 和 10mg/kg/d，这与人类的日常暴露水平相当，以探索其在 PCOS 发展中的潜在作用。研究结果表明，DEHP 暴露降低了卵巢和子宫系数，减少了原始卵泡的积累，增加了卵巢组织中闭锁和囊性卵泡以及纤维化的发生率，改变了血清激素水平，升高了血糖水平和胰岛素抵抗，扰乱了内分泌系统，导致卵巢组织发生明显的氧化损伤。这些结果表明 DEHP 暴露可能导致类似于 PCOS 的病变发展。通过分析蛋白质组的差异表达，并进行 GO 和 KEGG 富集分析，我们发现它们主要富集在代谢途径和 PPAR 信号通路中。我们证实 DEHP 暴露激活的 PPARγ 信号通路与 PCOS 样病变的出现有关。这项研究为 DEHP 暴露与 PCOS 之间的关联提供了直接的体内实验证据。
