Effects of high levels of androgens on oocyte maturation and potential regulatory role of retinoic acid

Abstract

Aims

Polycystic ovary syndrome (PCOS) is a prevalent condition among women, characterized by hyperandrogenism. This study aims to investigate the underlying mechanisms by which testosterone impact oocyte maturation and potential methods for addressing this condition.

Materials and methods

Testosterone propionate (TP) was incorporated into the oocyte maturation medium to simulate the typical hyperandrogenic environment associated with PCOS, facilitating an investigation the effect of hyperandrogen on oocyte maturation in vitro. The gene expression profiles of porcine cumulus-oocyte complexes (COCs) during in vitro maturation (IVM) following TP treatment were analyzed using RNA-seq.

Key findings

TP downregulated two genes, TNFAIP6 and EREG, associated with follicular development process. Additionally, GSEA analysis indicated that TP upregulated the retinol metabolism gene set. Both TP and retinoic acid (RA) were added to the oocyte maturation medium. Subsequently, we evaluated the molecular characteristics of COCs in various treatment groups and assessed the blastocyst formation rate following parthenogenetic activation of COCs. The results indicated that RA effectively reversed TP-induced meiotic repression by downregulating the elevated expression level of WEE2 in TP-treated oocytes. However, RA exhibited distinct effects on TP-induced alterations in gene expression, including EREG and TNFAIP6, at different stages.

Significance

RA could mitigate the adverse effects of hyperandrogenism on oocytes during maturation. Moreover, RA and testosterone exert a dual regulatory effect on extracellular matrix remodeling in cumulus cells. These findings suggest the potential therapeutic application of RA in androgen-induced PCOS.