Non-canonical WNT5A is a potential regulator of granulosa cell function in cattle

The WNT family has been implicated in follicular development in rodents, however, the role of WNTs in the follicle of monovulatory species is poorly understood. The objective of this study was to determine the potential roles of WNTs in bovine granulosa cell function. Cells cultured in serum-free medium expressed mRNA encoding WNT2B, WNT5B and WNT5A. Levels of WNT5A, but not of WNT2B or WNT5B mRNA, were down-regulated by FSH. Addition of WNT5A to cultured cells suppressed FSH-stimulated estradiol and progesterone secretion, and levels of mRNA encoding the steroidogenic enzymes CYP19A1, CYP11A1 and the FSH receptor, but had no effect on cell proliferation or apoptosis. Immunoblot experiments showed that WNT5A reduced activation of CTNNB1 and stimulated phosphorylation of MAPK8 and JUN proteins. We conclude that WNT5A is a negative regulator of FSH-stimulated granulosa cell steroidogenesis, and that it acts by suppressing canonical WNT signaling activity and inducing the non-canonical MAPK8/JUN pathway.