Targeted Deletion of NR2F2 and VCAM1 in Theca Cells Impacts Ovarian Follicular Development: Insights Into Polycystic Ovary Syndrome?†

Authors

Nicholes R Candelaria
JoAnne S Richards

Publication Date

4-11-2024

Journal

Biology of Reproduction

DOI

10.1093/biolre/ioae010

PMID

38224314

PMCID

PMC11017119

PubMedCentral® Posted Date

1-15-2024

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Animals, Female, Mice, Androgens, COUP Transcription Factor II, Granulosa Cells, Polycystic Ovary Syndrome, Theca Cells, Vascular Cell Adhesion Molecule-1

Abstract

Defining features of polycystic ovary syndrome (PCOS) include elevated expression of steroidogenic genes, theca cell androgen biosynthesis, and peripheral levels of androgens. In previous studies, we identified vascular cell adhesion molecule 1 (VCAM1) as a selective androgen target gene in specific NR2F2/SF1 (+/+) theca cells. By deleting NR2F2 and VCAM1 selectively in CYP17A1 theca cells in mice, we documented that NR2F2 and VCAM1 impact distinct and sometimes opposing theca cell functions that alter ovarian follicular development in vivo: including major changes in ovarian morphology, steroidogenesis, gene expression profiles, immunolocalization images (NR5A1, CYP11A1, NOTCH1, CYP17A1, INSL3, VCAM1, NR2F2) as well as granulosa cell functions. We propose that theca cells impact follicle integrity by regulating androgen production and action, as well as granulosa cell differentiation/luteinization in response to androgens and gonadotropins that may underlie PCOS.