AR-mediated YBX3 suppresses oocyte meiotic resumption in polycystic ovary syndrome by attenuating Pde3A and Ccnb1 expression.

BACKGROUND

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder with a detrimental effect on reproductive outcomes due to compromised oocyte quality. The exact mechanism of hyperandrogen-induced anovulation in PCOS is largely unknown to date. The maintenance of oocyte meiotic arrest is primarily attributed to high cytoplasmic concentrations of cyclic adenosine monophosphate (cAMP), which is hydrolyzed by Pde3a.

METHODS

To evaluate oocyte maturation, 3-week-old ICR mice were randomized into four treatment groups: control, dehydroepiandrosterone (DHEA), Ybx3 conditional knockout out (CKO, Ybx3 Flox/Flox; GDF9-Cre) and Ybx3 conditional knockout out + DHEA (CKO+DHEA). Subsequently ovaries were fixed and sectioned (for follicle counting), oocytes were collected and cultured (for in vitro maturation and further analysis).

RESULTS

The HE staining of ovaries revealed that the CKO+DHEA group had a significantly higher number of corpora lutea (P < 0.05) than the DHEA group. Hoechst staining revealed that no metaphase I (MI) oocytes were detected in DHEA group, whereas CKO+DHEA group showed 6.56% of MI oocytes. CKO+CHEA oocytes displayed an increased GVBD rate than DHEA group (P < 0.05). Dual luciferase reporter assay validated AR plasmid significantly induced the dual-luciferase activity of wild type pGL3-Ybx3 by 5.1 times (P < 0.05), while only increasing the activity of mutant type pGL3-Ybx3 1–3 by 3.6, 2.7 and 3.9 times (P < 0.05).

CONCLUSION

This study deepens our understanding of the molecular mechanisms underlying oocyte meiotic arrest in polycystic ovaries and highlight the therapeutic potential of Ybx3 as a complementary therapeutic target for hyperandrogen-induced anovulation in PCOS patients.