ArticleStem cell research & therapy2019
Hedgehog pathway inhibition causes primary follicle atresia and decreases female germline stem cell proliferation capacity or stemness.
Article in Stem cell research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 35 citations in OpenAlex.
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- Molecular evidence for early deuterostome origins of ovarian cell types and neuroendocrine control of reproduction.Nature communications · 2026Article
- Spatial transcriptomics in the human adult ovary: insights into key signalling pathways during follicular atresia.Human reproduction (Oxford, England) · 2026Article
- Network pharmacology uncovers that secoisolariciresinol diglucoside ameliorate premature ovarian insufficiency via PI3K/Akt pathway.Scientific reports · 2025Article
- The role of growth hormone in assisted reproductive technology for patients with diminished ovarian reserve: from signaling pathways to clinical applications.Frontiers in endocrinology · 2025Review
- Ovarian microenvironment: challenges and opportunities in protecting against chemotherapy-associated ovarian damage.Human reproduction update · 2024Review
- Comparison of ovarian mRNA expression levels in wild and hatchery-produced greater amberjack Seriola dumerili.Scientific reports · 2024Article
- 3D hUC-MSC spheroids exhibit superior resistance to autophagy and apoptosis of granulosa cells in POF rat model.Reproduction (Cambridge, England) · 2024Article
- Polyamines in Ovarian Aging and Disease.International journal of molecular sciences · 2023Review
- Review
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- Germline stem cells in human.Signal transduction and targeted therapy · 2022Review
- The role of oxidative stress in ovarian aging: a review.Journal of ovarian research · 2022Review
- Ubiquitin-like modifier 1 ligating enzyme 1 relieves cisplatin-induced premature ovarian failure by reducing endoplasmic reticulum stress in granulosa cells.Reproductive biology and endocrinology : RB&E · 2022Article
- MicroRNAs with non-additive expression in the ovary of hybrid hens target genes enriched in key reproductive pathways that may influence heterosis for egg laying traits.Frontiers in genetics · 2022Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFollicle depletion is one of the causes of premature ovarian failure (POF) and primary ovarian insufficiency (POI). Hence, maintenance of a certain number of female germline stem cells (FGSCs) is optimal to produce oocytes and replenish the primordial follicle pool. The mechanism that regulates proliferation or stemness of FGSCs could contribute to restoring ovarian function, but it remains uncharacterized in postnatal mammalian ovaries. This study aims to investigate the mechanism by which inhibiting the activity of the hedgehog (Hh) signaling pathway regulates follicle development and FGSC proliferation. METHODS AND
resultsTo understand the role of the Hh pathway in ovarian aging, we measured Hh signaling activity at different reproductive ages and the correlation between them in physiological and pathological mice. Furthermore, we evaluated the follicle number and development and the changes in FGSC proliferation or stemness after blocking the Hh pathway in vitro and in vivo. In addition, we aimed to explain one of the mechanisms for the FGSC phenotype changes induced by treatment with the Hh pathway-specific inhibitor GANT61 via oxidative stress and apoptosis. The results show that the activity of Hh signaling is decreased in the ovaries in physiological aging and POF models, which is consistent with the trend of expression levels of the germline stem cell markers Mvh and Oct4. In vitro, blocking the Hh pathway causes follicular developmental disorders and depletes ovarian germ cells and FGSCs after treating ovaries with GANT61. The proliferation or stemness of cultured primary FGSCs is reduced when Hh activity is blocked. Our results show that the antioxidative enzyme level and the ratio of Bcl-2/Bax decrease, the expression level of caspase 3 increases, the mitochondrial membrane potential is abnormal, and ROS accumulate in this system.
conclusionsWe observed that the inhibition of the Hh signaling pathway with GANT61 could reduce primordial follicle number and decrease FGSC reproductive capacity or stemness through oxidative damage and apoptosis.
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