Exosomal miR-143-3p derived from follicular fluid promotes granulosa cell apoptosis by targeting BMPR1A in polycystic ovary syndrome

Abstract

AbstractPolycystic ovary syndrome (PCOS) is an endocrine disorder that occurs in women of reproductive age. Anovulation caused by abnormal follicular development is still the main characteristic of PCOS patients with infertile. Granulosa cell (GC) is an important part of the follicular microenvironment, the dysfunction of which can affect follicular development. Increasing evidence indicates that exosomal miRNAs derived from the follicular fluid (FF) of patients play critical roles during PCOS. However, which follicular fluid-derived exosomal miRNAs play a pivotal role in controlling granulosa cell function and consequently follicular development remain largely unknown, as does the underlying mechanism. Herein, we showed that miR-143-3p is highly expressed in the follicular fluid exosomes of patients with PCOS and can be delivered into granulosa cells. Furthermore, functional experiments showed that translocated miR-143-3p promoted granulosa cell apoptosis, which is important in follicle development. Mechanistically, BMPR1A was identified as a direct target of miR-143-3p. Overexpression of BMPR1A reversed the effects of exosomal miR-143-3p on GC apoptosis and proliferation by activating the Smad1/5/8 signaling pathway. These results demonstrate that miR-143-3p-containing exosomes derived from PCOS follicular fluid promoted granulosa cell apoptosis by targeting BMPR1A and blocking the Smad1/5/8 signaling pathway. Our findings provide a novel mechanism underlying the roles of exosomal-miRNAs in the follicular fluid of PCOS patients and facilitate the development of therapeutic strategies for PCOS.