ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
LRRC4 Deficiency Drives Premature Ovarian Insufficiency by Disrupting Metabolic Homeostasis in Granulosa Cells.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The interaction between endoplasmic reticulum stress and ferroptosis in ovarian diseases.Journal of ovarian research · 2026Pooled it
- Engineering ovarian asymmetric mechanical niches in a dual-layer microcavity array enhances mouse secondary follicle development and oocyte competence.Bioactive materials · 2027Article
- SIRT1 deacetylates PKM2 to constrain lactate production and protect against premature ovarian insufficiency.Life medicine · 2026Article
- Spatial Transcriptomic Atlas Reveals That Forkhead Box O3-Mediated Mitochondrial Dynamics Imbalance Drives Premature Ovarian Insufficiency in Mice.Aging cell · 2026Article
- [Chronic iron overload induces diminished ovarian reserve in miceNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- 630 nm LED phototherapy enhances ovarian function and fertility potential in advanced reproductive age females.Bioengineering & translational medicine · 2026Article
- Review
- Circadian rhythm disruption declines oocyte quality for fertility via PTEN/AKT pathway.Protein & cell · 2026Article
- Targeting MFF succinylation: a novel therapeutic strategy for premature ovarian insufficiency by restoring mitochondrial dynamics in granulosa cells.Journal of ovarian research · 2026Review
- Female Aging Affects Coilin Pattern in Mouse Cumulus Cells.Journal of developmental biology · 2026Article
- Recent advances in methods for establishing animal models of premature ovarian failure.Journal of ovarian research · 2025Review
- Review
- LRRC4 Deficiency Drives Premature Ovarian Insufficiency by Disrupting Metabolic Homeostasis in Granulosa Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
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Authors and funding
6 authors.
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Abstract
Premature ovarian insufficiency (POI), defined by early loss of ovarian activity before the age of 40 years, is the leading cause of infertility and systematic aging in women, posing a public health challenge worldwide. However, its molecular etiology and therapeutic options are still lacking. Here, leucine-rich repeat containing 4 (LRRC4) is identified as a critical regulator of folliculogenesis expressed in granulosa cells (GCs), which contributes to ovarian reserve maintenance. LRRC4 deficiency triggers defective oocyte maturation and excessive follicular atresia through inhibition of GC differentiation and ultimately leads to POI. Mechanistically, LRRC4 balances mitochondrial fission and fusion to inhibit excessive mitophagy by promoting the K48-linked ubiquitination degradation of Yes-associated protein (YAP), thereby maintaining the metabolic homeostasis of mitochondrial aerobic respiration and glycolysis. Importantly, targeting LRRC4 normalized follicular development and ovarian function in POI model mice. In conclusion, these data reveal the novel pathogenesis of POI and suggest that LRRC4 is a potential target for the diagnosis and treatment of POI.
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