Exposure to environmental doses of DEHP causes phenotypes of polycystic ovary syndrome.

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.