ArticleEBioMedicine2020
Up-regulated FHL2 inhibits ovulation through interacting with androgen receptor and ERK1/2 in polycystic ovary syndrome.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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25 citing papers in PubMed, 48 citations in OpenAlex.
- Deconstructing the RAGE signaling maze: the molecular key to opening a new dimension of ovarian anti-aging.Experimental & molecular medicine · 2026Review
- The Effect of AMH on Folliculogenesis.Reproductive sciences (Thousand Oaks, Calif.) · 2025Review
- [Role of hyaluronic acid synthases in female infertility-related diseases].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- CCAAT/enhancer binding protein beta (C/EBPβ) regulates the formation of the ovarian reserve.Communications biology · 2025Article
- Overexpression of LIM Homeodomain GeneBiology · 2025Article
- The roles of MAPK signaling pathway in ovarian folliculogenesis.Journal of ovarian research · 2025Review
- Role of Granulosa Cell Dysfunction in Women Infertility Associated with Polycystic Ovary Syndrome and Obesity.Biomolecules · 2025Review
- Hyperandrogen-induced imbalance of FOXO4-AR regulatory loop contributes to ovulatory disorders in polycystic ovary syndrome.Molecular therapy. Nucleic acids · 2025Article
- Downregulation of FASN in granulosa cells and its impact on ovulatory dysfunction in PCOS.Journal of ovarian research · 2025Article
- Decreased neurotensin induces ovulatory dysfunction via the NTSR1/ERK/EGR1 axis in polycystic ovary syndrome.Frontiers of medicine · 2025Article
- Hsa-miR-92b-3p Targeting FHL2 to Enhance Radiosensitivity of Nasopharyngeal Carcinoma.Biochemical genetics · 2025Article
- Formononetin ameliorates polycystic ovary syndrome through suppressing NLRP3 inflammasome.Molecular medicine (Cambridge, Mass.) · 2025Article
- Effects of the FHL2 gene on the development of subcutaneous and intramuscular adipocytes in goats.BMC genomics · 2024Article
- Dysfunction of Human Estrogen Signaling as a Novel Molecular Signature of Polycystic Ovary Syndrome.International journal of molecular sciences · 2023Article
- Current Advances in Cellular Approaches for Pathophysiology and Treatment of Polycystic Ovary Syndrome.Cells · 2023Review
- Comprehensive pan-cancer analysis identifies FHL2 associated with poor prognosis in lung adenocarcinoma.Translational cancer research · 2023Article
- Prolactin Regulates Ovine Ovarian Granulosa Cell Apoptosis by Affecting the Expression ofInternational journal of molecular sciences · 2023Article
- FHL2 deficiency impairs follicular development and fertility by attenuating EGF/EGFR/YAP signaling in ovarian granulosa cells.Cell death & disease · 2023Article
- SDNOR, a Novel Antioxidative lncRNA, Is Essential for Maintaining the Normal State and Function of Porcine Follicular Granulosa Cells.Antioxidants (Basel, Switzerland) · 2023Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe ovulatory dysfunction mechanisms underlying polycystic ovary syndrome (PCOS) are not completely understood. There is no effective therapy for PCOS so far.
methodsWe measured the expression of four and a half LIM domain 2 (FHL2) and other related-genes in human granulosa cells (hGCs) from patients with and without PCOS. To minimise the heterogeneity of patients with PCOS, we only included PCOS patients meeting all three criteria according to the revised Rotterdam consensus. The in vitro effects of FHL2 on ovulatory genes and the underlying mechanisms were examined in KGN cells. The role of FHL2 in ovulation was investigated in vivo by overexpressing FHL2 in rat ovaries via intrabursal lentivirus injection.
findingsIncreased FHL2 and androgen receptor (AR) expression and decreased CCAAT/enhancer-binding protein β (C/EBPβ) expression were observed in hGCs from patients with PCOS. FHL2 inhibited the expression of ovulation-related genes, including phosphorylated ERK1/2, C/EBPβ, COX2 and HAS2 in KGN cells. It was partially by interacting with AR to act as its co-regulator to inhibit C/EBPβ expression and by binding to ERK1/2 to inhibit its phosphorylation. Moreover, FHL2 abundance in hGCs was positively correlated with the basal serum testosterone concentration of patients with PCOS, and dihydrotestosterone (DHT)-induced FHL2 upregulation was mediated by AR signalling in KGN cells. Additionally, lentiviral-mediated functional FHL2 overexpression in rat ovaries for 1 week contributed to an impaired superovulatory response, displaying decreased numbers of retrieved oocytes and a lower MII oocyte rate. 3-week FHL2 overexpression rat models without superovulation led to acyclicity and polycystic ovary morphology.
interpretationOur findings provide novel insights into the mechanisms underlying the pathogenesis of PCOS, suggesting that FHL2 could be a potential treatment target for ovulatory obstacles in PCOS. FUND: National Key Research and Development Program of China, National Natural Science Foundation, National Institutes of Health project and Shanghai Commission of Science and Technology.
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