ArticleCell death and differentiation2020
R-spondin2 signaling is required for oocyte-driven intercellular communication and follicular growth.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 46 citations in OpenAlex.
- Anti-Müllerian hormone induces a reversible quiescence-associated secretory phenotype in preantral follicles†.Biology of reproduction · 2026Article
- Hypo-glycosylated FSH enhances the ovarian microenvironment for follicular development compared to fully glycosylated FSH.Cell communication and signaling : CCS · 2025Article
- RSPO2 Coordinates with GDF9:BMP15 Heterodimers to Promote Granulosa Cell and Oocyte Development in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- β-Nicotinamide Mononucleotide Reduces Oxidative Stress and Improves Steroidogenesis in Granulosa Cells Associated with Sheep Prolificacy via Activating AMPK Pathway.Antioxidants (Basel, Switzerland) · 2024Article
- RSPO2 as Wnt signaling enabler: Important roles in cancer development and therapeutic opportunities.Genes & diseases · 2024Review
- Transcriptomic signatures of WNT-driven pathways and granulosa cell-oocyte interactions during primordial follicle activation.PloS one · 2024Article
- Mesenchymal stem cell-derived apoptotic vesicles ameliorate impaired ovarian folliculogenesis in polycystic ovary syndrome and ovarian aging by targeting WNT signaling.Theranostics · 2024Article
- Polycomb repressive complex 1 modulates granulosa cell proliferation in early folliculogenesis to support female reproduction.Theranostics · 2024Article
- R-spondin family biology and emerging linkages to cancer.Annals of medicine · 2023Review
- Cyanidin-3-O-Glucoside Rescues Zearalenone-Induced Apoptosis via the ITGA7-PI3K-AKT Signaling Pathway in Porcine Ovarian Granulosa Cells.International journal of molecular sciences · 2023Article
- Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients.Frontiers in physiology · 2023Review
- The biological functions and related signaling pathways of SPON2.Frontiers in oncology · 2023Review
- Article
- RSPO2 promotes progression of ovarian cancer through dual receptor-mediated FAK/Src signaling activation.iScience · 2022Article
- Bidirectional communication in oogenesis: a dynamic conversation in mice and Drosophila.Trends in cell biology · 2022Review
- Transcription Analysis for Core Networks of lncRNAs-mRNAs: Implication for Potential Role in Sterility ofBiology · 2022Article
- RSPO2 and RANKL signal through LGR4 to regulate osteoclastic premetastatic niche formation and bone metastasis.The Journal of clinical investigation · 2022Article
- Single-Cell Transcriptomics Analysis of Human Small Antral Follicles.International journal of molecular sciences · 2021Article
- DNA methylation mediated RSPO2 to promote follicular development in mammals.Cell death & disease · 2021Article
- WNT signaling in pre-granulosa cells is required for ovarian folliculogenesis and female fertility.Development (Cambridge, England) · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
R-spondin2 (RSPO2) is a member of the R-spondin family, which are secreted activators of the WNT/β-catenin (CTNNB1) signaling pathway. In the mouse postnatal ovary, WNT/CTNNB1 signaling is active in the oocyte and in the neighboring supporting cells, the granulosa cells. Although the role of Rspo2 has been previously studied using in vitro experiments, the results are conflicting and the in vivo ovarian function of Rspo2 remains unclear. In the present study, we found that RSPO2/Rspo2 expression is restricted to the oocyte of developing follicles in both human and mouse ovaries from the beginning of the follicular growth. In mice, genetic deletion of Rspo2 does not impair oocyte growth, but instead prevents cell cycle progression of neighboring granulosa cells, thus resulting in an arrest of follicular growth. We further show this cell cycle arrest to be independent of growth promoting GDF9 signaling, but rather associated with a downregulation of WNT/CTNNB1 signaling in granulosa cells. To confirm the contribution of WNT/CTNNB1 signaling in granulosa cell proliferation, we induced cell type specific deletion of Ctnnb1 postnatally. Strikingly, follicles lacking Ctnnb1 failed to develop beyond the primary stage. These results show that RSPO2 acts in a paracrine manner to sustain granulosa cell proliferation in early developing follicles. Taken together, our data demonstrate that the activation of WNT/CTNNB1 signaling by RSPO2 is essential for oocyte-granulosa cell interactions that drive maturation of the ovarian follicles and eventually female fertility.
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