WNT Signaling in Ovarian Follicle Development
Summary
WNT signalling comprises a family of secreted glycoproteins that orchestrate key events in ovarian follicle maturation, from the activation of dormant primordial follicles to the growth of antral follicles and eventual ovulation. In the canonical pathway, WNT ligands bind Frizzled receptors and LRP co-receptors to stabilise β-catenin, which enters the nucleus to modulate gene transcription. Non-canonical routes operate independently of β-catenin, influencing cell polarity and calcium fluxes. Within the ovarian niche, oocytes, granulosa cells and theca cells engage in reciprocal paracrine and autocrine crosstalk mediated by WNT ligands, secreted antagonists (such as SFRPs and DKKs) and enhancers (such as R-spondins). This dynamic signalling network governs granulosa cell proliferation, steroidogenesis, follicular survival and oocyte competence. Aberrant WNT activation or inhibition underlies disorders of folliculogenesis, including polycystic ovarian syndrome and age-related decline in oocyte quality. Emerging insights have revealed vesicle-based delivery of WNT modulators and novel intracellular cross-talk with metabolic sensors, highlighting potential therapeutic avenues to preserve or restore fertility.
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WNT Signaling in Ovarian Follicle Development publication trend
The graph below shows the total number of articles in wnt signaling in ovarian follicle development across all publications each year (not limited to Nature Index journals).
Technical terms
WNT signalling: A group of pathways triggered by WNT ligands that regulate cell fate, proliferation and adhesion.
Canonical pathway: The β-catenin-dependent branch of WNT signalling that influences gene transcription.
Granulosa cells: Somatic cells surrounding the oocyte that produce steroids and growth factors.
Theca cells: Ovarian cells that cooperate with granulosa cells to synthesise androgens and oestrogens.
Folliculogenesis: The process of follicle activation, growth and maturation leading to ovulation.
SFRP4: A secreted frizzled-related protein that antagonises WNT pathways and modulates granulosa cell function.
RSPO2: A secreted enhancer of WNT/β-catenin signalling produced by oocytes to support granulosa cell proliferation.
Apoptotic vesicles: Membrane-bound particles released by dying cells that carry signalling proteins and modulators.
β-catenin: A central effector of canonical WNT signalling that translocates to the nucleus to drive transcription.
GSK3β: A kinase that phosphorylates β-catenin targeting it for degradation; also involved in metabolic signalling cascades.
References
- Mesenchymal stem cell-derived apoptotic vesicles ameliorate impaired ovarian folliculogenesis in polycystic ovary syndrome and ovarian aging by targeting WNT signaling. Theranostics (2024).
- SFRP4 promotes autophagy and blunts FSH responsiveness through inhibition of AKT signaling in ovarian granulosa cells. Cell Communication and Signaling (2024).
- R-spondin2 signaling is required for oocyte-driven intercellular communication and follicular growth. Cell Death & Differentiation (2020).
- The Signaling Pathways Involved in Ovarian Follicle Development. Frontiers in Physiology (2021).
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