ArticleMolecules (Basel, Switzerland)2021
Orexin-A Regulates Follicular Growth, Proliferation, Cell Cycle and Apoptosis in Mouse Primary Granulosa Cells via the AKT/ERK Signaling Pathway.
Article in Molecules (Basel, Switzerland), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Beyond apoptosis: evidence of other regulated cell death pathways in the ovary throughout development and life.Human reproduction update · 2023Pooled it
- A NovelThe world journal of men's health · 2026Article
- [Neuroendocrine regulation of the reproductive system: integration of research of neuropeptide and experimental pathophysiology of amenorrhea of different genesis (literature review)].Problemy endokrinologii · 2026Review
- Review
- The roles of MAPK signaling pathway in ovarian folliculogenesis.Journal of ovarian research · 2025Review
- LncRNA NEAT1 participates in diminished ovarian reserve by affecting granulosa cell apoptosis and estradiol synthesis via the miR-204-5p/ESR1 axis.Journal of ovarian research · 2025Article
- Pyruvate Regulates the Expression ofCells · 2025Article
- Independent Elevation of Leptin and Reduction of Protective Adipokines in Polycystic Ovary Syndrome: A BMI-Matched Case-Control Study.International journal of women's health · 2025Article
- Signal transduction, dimerization, and therapeutic targeting of Orexin and receptor systems.Frontiers in pharmacology · 2025Review
- Nicotinamide Mononucleotide Restores NADAntioxidants (Basel, Switzerland) · 2024Article
- Article
- Mechanism study of YangJing ZhongYu decoction on regulating mitochondrial dynamics of ovarian granular cells and improving diminished ovarian reserve.Journal of ovarian research · 2024Article
- The Role of Mannitol and Vitamin D in Ovarian Ischemia/Reperfusion Injury in Rats with Acute Abdominal.Current issues in molecular biology · 2024Article
- Human Amniotic Epithelial Stem Cells Alleviate Autoimmune Premature Ovarian Insufficiency in Mice by Targeting Granulosa Cells via AKT/ERK Pathways.Stem cell reviews and reports · 2024Article
- Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.Heliyon · 2024Review
- Sex-specific role of high-fat diet and stress on behavior, energy metabolism, and the ventromedial hypothalamus.Biology of sex differences · 2024Article
- Article
- Orexins in apoptosis: a dual regulatory role.Frontiers in cellular neuroscience · 2024Review
- Revolutionizing Infertility Management through Novel Peptide-based Targets.Current protein & peptide science · 2024Review
- Orexin antagonism and substance-P: Effects and interactions on polycystic ovary syndrome in the wistar rats.Journal of ovarian research · 2023Article
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Granulosa cells (GCs) are essential for follicular growth, development, and atresia. The orexin-A (OXA) neuropeptide is widely involved in the regulation of various biological functions. OXA selectively binds to orexin receptor type 1 (OX1R) and mediates all its biological actions via OX1R. This study aimed to explore the expression of OXA and OX1R and their regulatory role in GCs proliferation, cell cycle progression, apoptosis, oocyte maturation, and underlying molecular mechanisms of these processes and elucidate its novel signaling pathway. Western blotting and RT-qPCR showed that OXA and OX1R were expressed during different developmental stages of GCs, and siRNA transfection successfully inhibited the expression of OX1R at the translational and transcriptional levels. Flow cytometry revealed that OX1R knockdown upregulated GCs apoptosis and triggered S-phase arrest in cell cycle progression. RT-qPCR and Western blotting showed significantly reduced expression of Bcl-2 and elevated expression of Bax, caspase-3, TNF-α, and P21 in OX1R-silenced GCs. Furthermore, the CCK-8 assay showed that knockdown of OX1R suppressed GCs proliferation by downregulating the expression of PCNA, a proliferation marker gene, at the translational and transcriptional levels. Western blotting revealed that knockdown of OX1R resulted in a considerable decrease of the phosphorylation level of the AKT and ERK1/2 proteins, indicating that the AKT/ERK1/2 pathway is involved in regulating GCs proliferation and apoptosis. In addition, OX1R silencing enhanced the mRNA expression of GDF9 and suppressed the mRNA expression of BMP15 in mouse GCs. Collectively, these results reveal a novel regulatory role of OXA in the development of GCs and folliculogenesis by regulating proliferation, apoptosis, and cell cycle progression. Therefore, OXA can be a promising therapeutic agent for female infertility.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.