ArticleProceedings of the National Academy of Sciences of the United States of America2015
Intercellular signaling via cyclic GMP diffusion through gap junctions restarts meiosis in mouse ovarian follicles.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 167 citations in OpenAlex.
- Proprotein convertase activity regulates cumulus-oocyte-complex matrix integrity and cumulus cell migration during ovulation via a GDF9-dependent mechanism.bioRxiv : the preprint server for biology · 2026Article
- Molecular Mechanisms of Negative Effect of Systemic Lupus Erythematosus on Oogenesis and Meiotic Processes in Oocytes.International journal of molecular sciences · 2026Review
- Extracellular Matrix Remodeling and Matrix Metalloproteinases in Ovarian Function and Infertility.International journal of molecular sciences · 2026Review
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- Effect of cAMP concentration on apoptosis of sheep granulosa cells in vitro.In vitro cellular & developmental biology. Animal · 2026Article
- Advances, Mechanisms, and Clinical Perspectives for the In Vitro Maturation of Human Oocytes.International journal of molecular sciences · 2025Review
- Intercellular diffusion of cyclic nucleotides followed by gap junction closure restarts meiosis in mouse preovulatory follicles.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Metabolomic Analysis of Sea Cucumber Ovum Hydrolysates in Cyclophosphamide-Induced Premature Ovarian Failure.Foods (Basel, Switzerland) · 2025Article
- Luteinizing Hormone Preserves Oocyte-Granulosa Cell Communication in Growing Follicles Exposed to Chemotherapy with Alkylating Agents at the Primordial Stage in a Mouse Model.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Article
- Granulosa Cells Alone, Without Theca Cells, Can Mediate LH-induced Oocyte Meiotic Resumption.Endocrinology · 2024Article
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase†.Biology of reproduction · 2024Article
- RNAseq analysis of oocyte maturation from the germinal vesicle stage to metaphase II in pig and human.PloS one · 2024Article
- The molecular regulatory mechanisms of meiotic arrest and resumption in Oocyte development and maturation.Reproductive biology and endocrinology : RB&E · 2023Review
- Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase.bioRxiv : the preprint server for biology · 2023Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- The Implications of Insufficient Zinc on the Generation of Oxidative Stress Leading to Decreased Oocyte Quality.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Developmental Hurdles That Can Compromise Pregnancy during the First Month of Gestation in Cattle.Animals : an open access journal from MDPI · 2023Review
- Betacellulin regulates gap junction intercellular communication by inducing the phosphorylation of connexin 43 in human granulosa-lutein cells.Journal of ovarian research · 2023Article
- The Caenorhabditis elegans innexin INX-20 regulates nociceptive behavioral sensitivity.Genetics · 2023Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Meiosis in mammalian oocytes is paused until luteinizing hormone (LH) activates receptors in the mural granulosa cells of the ovarian follicle. Prior work has established the central role of cyclic GMP (cGMP) from the granulosa cells in maintaining meiotic arrest, but it is not clear how binding of LH to receptors that are located up to 10 cell layers away from the oocyte lowers oocyte cGMP and restarts meiosis. Here, by visualizing intercellular trafficking of cGMP in real-time in live follicles from mice expressing a FRET sensor, we show that diffusion of cGMP through gap junctions is responsible not only for maintaining meiotic arrest, but also for rapid transmission of the signal that reinitiates meiosis from the follicle surface to the oocyte. Before LH exposure, the cGMP concentration throughout the follicle is at a uniformly high level of ∼2-4 μM. Then, within 1 min of LH application, cGMP begins to decrease in the peripheral granulosa cells. As a consequence, cGMP from the oocyte diffuses into the sink provided by the large granulosa cell volume, such that by 20 min the cGMP concentration in the follicle is uniformly low, ∼100 nM. The decrease in cGMP in the oocyte relieves the inhibition of the meiotic cell cycle. This direct demonstration that a physiological signal initiated by a stimulus in one region of an intact tissue can travel across many layers of cells via cyclic nucleotide diffusion through gap junctions could provide a general mechanism for diverse cellular processes.
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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.