Transcriptomic Signatures of WNT-Driven Pathways and Granulosa Cell-Oocyte Interactions during Primordial Follicle Activation

• DOI: 10.1101/2024.02.08.579446
• Publication Date: 2024-02-12T12:35:21Z
• Authors: Hinako M. Takase; Tappei Mishina; Tetsutaro Hayashi; Mika Yoshimura; Mariko Kuse; Itoshi Nikaido; Tomoya S. Kitajima
• Keywords: Granulosa cell

Abstract Primordial follicle activation (PFA) is a pivotal event in female reproductive biology, coordinating the transition from quiescent to growing follicles. This study employed comprehensive single-cell RNA sequencing gain insights into detailed regulatory mechanisms governing synchronized dormancy and between granulosa cells (GCs) oocytes with progression of PFA process. Wntless ( Wls ) conditional knockout (cKO) mice served as unique model, suppressing pre-GCs GCs, disrupting somatic cell-derived WNT signaling ovary. Our data revealed immediate transcriptomic changes GCs post-PFA cKO mice, leading divergent trajectory, while exhibited modest alterations. Subpopulation analysis identified molecular pathways affected by on GC maturation, along specific gene signatures linked dormant activated oocytes. Despite minimal evidence continuous up-regulation dormancy-related genes oocytes, loss (pre-)GCs impacted expression even before PFA, subsequently influencing them globally. The infertility observed was attributed compromised GC-oocyte crosstalk microenvironment for highlights role WNT-signaling pathway its signature, emphasizing importance intercellular orchestrating folliculogenesis. Author summary In mammalian ovaries, primordial follicles protect wasteful consumption. We explored complex dynamics critical process that underlies health, focus signaling. By utilizing mouse model disrupted signaling, our reveals novel during PFA. Single-cell transcriptome profiling uncovered distinct cell populations highlighted impact ovarian types. post-PFA, which affects their differentiation trajectories establishing function. further examined consequences microenvironments interactions, elucidated altered oocyte subclusters potential links infertility. These findings provide foundation understanding connections contributes valuable knowledge clinical relevance fertility.