ArticleHistochemistry and cell biology2020
CREB activity is required for mTORC1 signaling-induced primordial follicle activation in mice.
Article in Histochemistry and cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Piezo2FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Calcitriol is involved in maintaining primordial follicle reserve through the inhibition of the PI3K/Akt signaling pathway.Journal of ovarian research · 2026Article
- Transcriptome profiling of bovine preantral follicles during early folliculogenesis.Journal of animal science and biotechnology · 2026Article
- Ovarian aging: maintenance and activation of the primordial follicle pool.Journal of ovarian research · 2026Review
- Bone mesenchymal stem cells attenuate axonopathy in spinal cord of rats exposed to 2,5-hexanedione via NGF-dependent and -independent pathways.Molecular and cellular biochemistry · 2026Article
- The roles of MAPK signaling pathway in ovarian folliculogenesis.Journal of ovarian research · 2025Review
- Can vildagliptin protect against radiation-induced premature ovarian failure? Insights into the AMPK and AKT signaling pathways.BMC pharmacology & toxicology · 2025Article
- Structure-Based Modeling of the Gut Bacteria-Host Interactome Through Statistical Analysis of Domain-Domain Associations Using Machine Learning.Biotech (Basel (Switzerland)) · 2025Article
- Advances in ovarian follicle culture systems: exploring the interplay between cells, matrix, and ovarian architecture.Animal reproduction · 2025Article
- Berberine promotes primordial follicle activation and increases ovulated oocyte quantity in aged mice.Molecular medicine (Cambridge, Mass.) · 2024Article
- STAT3/LKB1 controls metastatic prostate cancer by regulating mTORC1/CREB pathway.Molecular cancer · 2023Article
- HucMSC-EVs Facilitate In Vitro Development of Maternally Aged Preantral Follicles and Oocytes.Stem cell reviews and reports · 2023Article
- Mechanisms of primordial follicle activation and new pregnancy opportunity for premature ovarian failure patients.Frontiers in physiology · 2023Review
- The metallic compound promotes primordial follicle activation and ameliorates fertility deficits in aged mice.Theranostics · 2023Article
- The Effect of Stimulation Protocols (GnRH Agonist vs. Antagonist) on the Activity of mTOR and Hippo Pathways of Ovarian Granulosa Cells and Its Potential Correlation with the Outcomes of In Vitro Fertilization: A Hypothesis.Journal of clinical medicine · 2022Article
- The Molecular Regulation in the Pathophysiology in Ovarian Aging.Aging and disease · 2021Review
- Revisiting the Impact of Local Leptin Signaling in Folliculogenesis and Oocyte Maturation in Obese Mothers.International journal of molecular sciences · 2021Review
- In focus in HCB.Histochemistry and cell biology · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In mammals, progressive activation of primordial follicles is essential for maintenance of the reproductive lifespan. Several reports have demonstrated that mitogen-activated protein kinases 3 and 1 (MAPK3/1)-mammalian target of rapamycin complex 1 (mTORC1) signaling in pre-granulosa cells promotes primordial follicle activation by increasing KIT ligand (KITL) expression and then stimulating phosphatidylinositol 3 kinase signaling in oocytes. However, the mechanism of mTORC1 signaling in the promotion of KITL expression is unclear. Immunofluorescence staining results showed that phosphorylated cyclic AMP response element-binding protein (CREB) was mainly expressed in pre-granulosa cells. The CREB inhibitor KG-501 and CREB knockdown by Creb siRNA significantly suppressed primordial follicle activation, reduced pre-granulosa cell proliferation and dramatically increased oocyte apoptosis. Western blotting results demonstrated that both the MAPK3/1 inhibitor U0126 and mTORC1 inhibitor rapamycin significantly decreased the levels of phosphorylated CREB, indicating that MAPK3/1-mTORC1 signaling is required for CREB activation. Furthermore, CREB could bind to the Kitl promoter region, and KG-501 significantly decreased the expression levels of KITL. In addition, KG-501 and CREB knockdown significantly decreased the levels of phosphorylated Akt, leading to a reduced number of oocytes with Foxo3a nuclear export. KG-501 also inhibited bpV (HOpic)-stimulated primordial follicle activation. Taken together, the results show that CREB is required for MAPK3/1-mTORC1 signaling-promoted KITL expression followed by the activation of primordial follicles.
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