Dynamics of YAP localization and transcript activity in human oocytes and granulosa cells across early-stage folliculogenesis: an exploratory investigation.

Abstract

Purpose: The transcription factor yes-associated protein (YAP) has been implicated in the regulation of murine follicle activation at the level of granulosa cells (GCs); however, less is known about its role in human folliculogenesis. This study aimed to explore the localization dynamics of YAP in the nucleus and cytoplasm of oocytes and granulosa cells in human ovarian follicles.

Methods: YAP nuclear localization and mRNA expression of its gene target, connective tissue growth factor (CCN2), were investigated in oocytes and GCs across primordial, transitioning primordial, primary, and secondary follicles in human ovarian cortical tissue cultured up to 48 h. Slow-frozen and thawed human ovarian cortex squares (10 × 10 × 1 mm) were cut into smaller tissue strips (1 × 5 × 1 mm), and these strips were either fixed immediately (Timepoint 0) or cultured for 6, 24, or 48 h (n = 3 per timepoint). We analyzed oocytes and GCs from a total of 562 human follicles-112 primordial, 373 transitioning primordial, 65 primary, and 12 secondary.

Results: Within each timepoint, YAP nuclear localization in GCs showed significantly greater abundance at the primary stages compared to the primordial stages but remained unchanged in oocytes. Furthermore, CCN2 mRNA expression in GCs increased significantly between the primordial and secondary stages of folliculogenesis, indicating YAP is transcriptionally active in granulosa cells of growing follicles.

Conclusion: Our findings provide the important insight that YAP activity in granulosa cells could be a key regulator within human follicles transitioning from primordial to primary stages, a role that is likely conserved between humans and mice.