Abstract

The extensive utilization of plastics has resulted in the emergence of di(2-ethylhexyl) phthalate (DEHP) as a major contaminant in the environment, posing serious implications for human and animal health. Multiple investigations suggest that exposure to DEHP impairs female reproductive capacity, causing depletion of primordial follicles and disruption of hormone production. However, the specific mechanisms by which DEHP influences ovarian development and function in females remain unclear. In our work, we conducted an in vivo study using a mouse model exposed to 200 mg/kg DEHP for 28 days. We found that exposure to DEHP inhibited ovarian development and follicle maturation, leading to decreased numbers of primary and antral follicles. Furthermore, we observed that exposure to DEHP destroyed mitochondrial dynamics in the ovary, leading to mitophagy and autophagy. Additionally, DEHP exposure induced oxidative stress and abnormal mitochondrial energy metabolism by inhibiting Sirt3/Sod2-regulated signaling pathway in the ovary. Furthermore, our findings showed that DEHP exposure caused ovarian DNA damage and apoptosis by inhibiting Akt/mTOR signaling cascade. In conclusion, our study shows that DEHP exposure profoundly impairs ovarian function through inhibiting Sirt3/Sod2 and Akt/mTOR signaling pathways. These results provide valuable insights into the detrimental effects of DEHP on the female reproductive system.