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

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-02-11 DOI:10.1016/j.lfs.2025.123463

Yongfeng Zhou , Qi Zhang , Ran Ding, Xinyuan Fan, Qi Li, Ziyi Li

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引用次数: 0

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.

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.