AUTHOR=Emery Alaknanda , Dunning Kylie R. , Dinh Doan T. , Akison Lisa K. , Robker Rebecca L. , Russell Darryl L. 

TITLE=Dynamic regulation of semaphorin 7A and adhesion receptors in ovarian follicle remodeling and ovulation

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=Volume 11 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2023.1261038

DOI=10.3389/fcell.2023.1261038

ISSN=2296-634X

ABSTRACT=The ovarian follicle is a complex structure that protects and matures the oocyte, then releases it through the controlled molecular and structural remodelling process of ovulation. The progesterone receptor (PGR) has been shown to be essential in regulating ovulation-related gene expression changes. In this study, we found disrupted expression of the cellular adhesion receptor gene Sema7a in the granulosa cells of PGR -/-mice during ovulation. We subsequently found that expression of Sema7a in preovulatory follicles is promoted by gonadotropins and hypoxia, establishing an assymetrical pattern with SEMA7a protein enriched at the apex of large antral follicles. Sema7a expression was downregulated through a PGR-dependent mechanism in the 30 periovulatory period, and the abundance of SEMA7A protein was reduced and assymetric pattern more homogeneous after ovulatory stimulus. Receptors for Sema7a can either repel or promote intercellular adhesion. During ovulation, striking inverse regulation of replusive Plxnc1 and adhesive Itga5/Itgb1 receptors likely contribute to the dramatic tissue remodelling. The adhesive receptor Itga5 was significantly increased in periovulatory granulosa cells and cumulus-oocyte complexes (COCs), and functional assays show periovulatory granulosa cells and COCs acquire increased adhesive phenotypes, while Sema7a repels granulosa cell contact. These findings suggest that the regulation of Sema7a and its associated receptors, along with the modulation of integrin α5, may be critical in establishing the multilaminar ovarian follicle structure and facilitating the remodeling and apical release of the cumulus-oocyte complex during ovulation. 40