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New anti-Müllerian hormone target genes involved in granulosa cell survival in women with polycystic ovary syndrome.

TitleNew anti-Müllerian hormone target genes involved in granulosa cell survival in women with polycystic ovary syndrome.
Publication TypeJournal Article
Year of Publication2020
AuthorsRacine, C, Genet, C, Bourgneuf, C, Dupont, C, Plisson-Petit, F, Sarry, J, Hennequet-Antier, C, Vigouroux, C, d'Argent, EMathieu, Pierre, A, Monniaux, D, Fabre, S, di Clemente, N
JournalJ Clin Endocrinol Metab
Date Published2020 Nov 28
ISSN1945-7197
Abstract

PURPOSE: A protective effect of anti-Müllerian hormone (AMH) on follicle atresia was recently demonstrated using long-term treatments, but this effect has never been supported by mechanistic studies. This work aimed to gain an insight into the mechanism of action of AMH on follicle atresia and on how this could account for the increased follicle pool observed in women with polycystic ovary syndrome (PCOS).

METHODS: In vivo and in vitro experiments were performed to study the effects of AMH on follicle atresia and on the proliferation and apoptosis of granulosa cells (GCs). RNA-sequencing was carried out to identify new AMH target genes in GCs. The expression of some of these genes in GCs from control and PCOS women was compared using microfluidic real time RT-quantitative PCR.

RESULTS: A short-term AMH treatment prevented follicle atresia in prepubertal mice. Consistent with this result, AMH inhibited apoptosis and promoted proliferation of different models of GCs. Moreover, integrative biology analyses of 965 AMH target genes identified in one of these GC models, confirmed that AMH had initiated a gene expression program favoring cell survival and proliferation. Finally, on 43 genes selected among the most up- and down-regulated AMH targets, eight genes were up-regulated in GCs isolated from PCOS women, of which five are involved in cell survival.

MAIN CONCLUSIONS: Our results provide for the first time cellular and molecular evidence that AMH protects follicles from atresia by controlling GC survival, and suggest that AMH could participate in the increased follicle pool of PCOS patients.

DOI10.1210/clinem/dgaa879
Alternate JournalJ Clin Endocrinol Metab
PubMed ID33247926