DEHP exposure to lactating mice affects ovarian hormone production and antral follicle development of offspring

Abstract Di (2-ethylhexyl) phthalate (DEHP) is widely used as a plastic additive and it could induce reproduction defects and fertility in mammals as environmental endocrine disruptor. However, the effects and potential mechanism of DEHP exposure during lactation stage on follicular development of offspring are still unclear. In this study, we found that the total primordial follicle number and antral follicles in the suckling of mice exposed to DEHP during lactation was significantly reduced. RNA-seq analysis results showed that the transcription levels of genes related to steroid production, ovarian hormone secretion and oxidative stress were significantly changed, which led to a decrease in 17β-estradiol and an increase in oxidative stress. The proportion of DNA damage marker γH2AX in the ovary of female suckling exposed to DEHP was significantly increased. We also found an increase in the level of ovarian apoptosis, and the proliferation of ovarian granulosa cells was inhibited. These alterations also lead to abnormal spindle and chromosome misalignment during oocyte maturation. Overall, our data indicate that lactation exposure to DEHP can affect the secretion of hormones and the development of antral follicles in suckling mice by affecting the secretion pathways of ovarian hormone enzymes and oxidative stress pathway.