ArticleScientific reports2019
SMAD3 directly regulates cell cycle genes to maintain arrest in granulosa cells of mouse primordial follicles.
Article in Scientific reports, 2019. 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, 51 citations in OpenAlex.
- Calcitriol is involved in maintaining primordial follicle reserve through the inhibition of the PI3K/Akt signaling pathway.Journal of ovarian research · 2026Article
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- All-trans retinoic acid modulates proliferation and apoptosis of secondary hair follicle-dermal papilla cells in cashmere goats via the TGF-Frontiers in veterinary science · 2026Article
- Building a resilient ovarian reserve: Early soma-oocyte interactions.Current topics in developmental biology · 2026Review
- A Dynamic Shift in Estrogen Receptor Expression During Granulosa Cell Differentiation in the Ovary.Endocrinology · 2025Article
- Article
- FOXL2 interaction with different binding partners regulates the dynamics of ovarian development.Science advances · 2024Article
- Integrated analysis reveals the regulatory mechanism of the neddylation inhibitor MLN4924 on the metabolic dysregulation in rabbit granulosa cells.BMC genomics · 2024Article
- HDAC6-dependent deacetylation of NGF dictates its ubiquitination and maintains primordial follicle dormancy.Theranostics · 2024Article
- Transcriptomic signatures of WNT-driven pathways and granulosa cell-oocyte interactions during primordial follicle activation.PloS one · 2024Article
- The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition.Cancers · 2023Review
- Making a good egg: human oocyte health, aging, and in vitro development.Physiological reviews · 2023Review
- Effect of aging on the formation and growth of colonic epithelial organoids by changes in cell cycle arrest through TGF-β-Smad3 signaling.Inflammation and regeneration · 2023Article
- A Subpathway and Target Gene Cluster-Based Approach Uncovers lncRNAs Associated with Human Primordial Follicle Activation.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 TGF-β/SMAD Signaling Pathway Prevents Follicular Atresia by Upregulating MORC2.International journal of molecular sciences · 2022Article
- Single-cell transcriptomics of staged oocytes and somatic cells reveal novel regulators of follicle activation.Reproduction (Cambridge, England) · 2022Article
- An intermediate state in trans-differentiation with proliferation, metabolic, and epigenetic switching.iScience · 2021Article
- Article
- Establishing and maintaining fertility: the importance of cell cycle arrest.Genes & development · 2021Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Primordial follicles, consisting of granulosa cell (GC)-enveloped oocytes are maintained in a state of developmental arrest until activated to grow. The mechanism that operates to maintain this arrested state in GCs is currently unknown. Here, we show the TGFβ-activated transcription factor SMAD3 is expressed in primordial GC nuclei alongside the cell cycle proteins, cyclin D2 (CCND2) and P27. Using neonatal C57/Bl6 mouse ovaries densely populated with primordial follicles, CCND2 protein co-localised and was detected in complex with P27 by immunofluorescence and co-immunoprecipitation, respectively. In the same tissue, SMAD3 co-precipitated with DNA sequences upstream of Ccnd2 and Myc transcription start sites implicating both as direct SMAD3 targets. In older ovaries follicle growth was associated with nuclear exclusion of SMAD3 and reduced P27 and CCND2 in GCs, alongside elevated Myc expression. Brief (2 H) exposure of neonatal ovaries to TGFβ1 (10 ng/ml) in vitro led to immediate dissociation of SMAD3 from the Ccnd2 and Myc promoters. This coincided with elevated Myc and phospho-S6, an indicator of mTOR signalling, followed by a small increase in mean primordial GC number after 48 H. These findings highlight a concentration-dependent role for TGFβ signalling in the maintenance and activation of primordial follicles, through SMAD-dependent and independent signalling pathways, respectively.
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