Effects of Androgen Excess-Related Metabolic Disturbances on Granulosa Cell Function and Follicular Development

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS....

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Published in:Frontiers in endocrinology (Lausanne) 2022-02, Vol.13, p.815968-815968
Main Authors: Liao, Baoying, Qi, Xinyu, Yun, Chuyu, Qiao, Jie, Pang, Yanli
Format: Article
Language:English
Subjects:
Androgens - pharmacology
Animals
Dehydroepiandrosterone
Endocrinology
Female
follicular development
Granulosa Cells
Humans
in vitro follicle culture
metabolic disorders
Mice
ovarian dysfunction
polycystic ovary syndrome
Polycystic Ovary Syndrome - metabolism
Steroids
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Summary:Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease in women of reproductive age. Ovarian dysfunction including abnormal steroid hormone synthesis and follicular arrest play a vital role in PCOS pathogenesis. Hyperandrogenemia is one of the important characteristics of PCOS. However, the mechanism of regulation and interaction between hyperandrogenism and ovulation abnormalities are not clear. To investigate androgen-related metabolic state in granulosa cells of PCOS patients, we identified the transcriptome characteristics of PCOS granulosa cells by RNA-seq. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed genes (DEGs) revealed that genes enriched in lipid metabolism pathway, fatty acid biosynthetic process and ovarian steroidogenesis pathway were abnormally expressed in PCOS granulosa cells in comparison with that in control. There are close interactions among these three pathways as identified by analysis of the protein-protein interaction (PPI) network of DEGs. Furthermore, mouse follicle culture system was established to explore the effect of high androgen and its related metabolic dysfunction on follicular growth and ovulation. RT-qPCR results showed that follicles cultured with dehydroepiandrosterone (DHEA) exhibited decreased expression levels of cumulus expansion-related genes ( , , and ) and oocyte maturation-related genes ( and ), which may be caused by impaired steroid hormone synthesis and lipid metabolism, thus inhibited follicular development and ovulation. Furthermore, the inhibition effect of DHEA on follicle development and ovulation was ameliorated by flutamide, an androgen receptor (AR) antagonist, suggesting the involvement of AR signaling. In summary, our study offers new insights into understanding the role of androgen excess induced granulosa cell metabolic disorder in ovarian dysfunction of PCOS patients.
ISSN:1664-2392
1664-2392
DOI:10.3389/fendo.2022.815968