Dynamics of WNT signaling components in the human ovary from development to adulthood.

Abstract

WNT signaling has been shown to play a pivotal role in mammalian gonad development and sex differentiation; however, its role in the developing human ovary has not been investigated. We analyzed a quantitative mass spectrometry dataset to determine the expression of WNT signaling components between 47 and 137 days of development and in adult ovarian cortex tissue. WNT signaling was identified within the top ten canonical pathways of proteins detected at every developmental stage examined. We further examined the specific localization of WNT signaling components glycogen synthase kinase 3 (GSK3B), frizzled 2 (FZD2), and β-catenin (CTNNB1) within ovarian tissue. GSK3B was nearly ubiquitously expressed during fetal development, while FZD2 was specific to germ cell nests during early development. β-catenin exhibited translocation from primarily membrane bound during early ovarian development to cytoplasmic and nuclear staining specifically in early primordial follicles in the fetal ovary. This cytoplasmic and nuclear β-catenin persisted in primordial follicles in adult ovarian tissue, but returned to membrane-bound localization in secondary follicles. We conclude that WNT signaling components are expressed in the human ovary from early to mid-gestation and remain in the adult ovary, and observed evidence for canonical WNT signaling only in the oocytes of primordial follicles. Together, these data are indicative of a role for canonical WNT signaling via β-catenin nuclear translocation during human follicle formation and follicle maintenance.