Detrimental effect of Bisphenol S in mouse germ cell cyst breakdown and primordial follicle assembly

The female reproductive lifespan is largely determined by the size of primordial follicle pool, which is established in early life. Bisphenol S (BPS), frequently present in plastic products used in daily life, has been demonstrated as an exogenous estrogen-like endocrine disrupting chemical interfering with the endocrine and reproductive systems. However, the molecular mechanisms of its reproductive toxicity remain to be determined. In the present study, we focused on the effect of BPS on the early ovarian folliculogenesis of mice. Our in vivo experiments showed that the treatment with BPS at 2 and 10 μg/kg body weight/day for 3 days induced abnormal germ cell cyst breakdown and primordial follicle assembly in the mouse ovary, further affecting later ovarian differentiation and reducing oocyte quality. In addition, our in vitro study demonstrated that BPS could interact with estrogen receptors (ERs) to induce phosphorylation of JNKs, which is responsible for reducing oocyte adhesion in cysts. Meanwhile, BPS exposure up-regulated Notch signaling pathway to increase the proliferation of granulosa cells precursors. Our study provided new evidence for the adverse effects of BPS on female reproduction, especially after perinatal exposure, and elucidated how it works.