ArticleThe Journal of clinical investigation2004
Cyclic nucleotide phosphodiesterase 3A-deficient mice as a model of female infertility.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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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.
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Who cites it
100 citing papers in PubMed, 245 citations in OpenAlex.
- Integrated genomic and transcriptomic analysis reveals candidate genes associated with reproductive performance in Hetian Black chickens.Poultry science · 2026Article
- Phosphodiesterase inhibitors as emerging therapeutics for skeletal disorders: A comprehensive review of mechanisms and repurposing potential.Bone reports · 2026Review
- The Role of PDE3A in Cancer.ACS omega · 2026Review
- Developmental regulation of Erk signaling by mitotic kinases.Science advances · 2026Article
- A phenotypicHuman reproduction open · 2026Article
- Intercellular cyclic nucleotide dynamics mediate oocyte meiosis in mammalian preovulatory follicles.Current topics in developmental biology · 2026Review
- The cAMP signaling pathway mediates photoperiod-induced follicle development in striped hamsters (Frontiers in endocrinology · 2026Article
- Roles of Cyclic Nucleotide Phosphodiesterases in Signal Transduction Pathways in the NematodeCells · 2025Review
- Pde3a and Pde3b regulation of murine pulmonary artery smooth muscle cell growth and metabolism.Physiological reports · 2024Article
- Icariin as a Treatment Proposal in Mammalian Reproduction.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Theophylline derivatives promote primordial follicle activation via cAMP-PI3K/Akt pathway and ameliorate fertility deficits in naturally aged mice.International journal of biological sciences · 2024Article
- Making a good egg: human oocyte health, aging, and in vitro development.Physiological reviews · 2023Review
- Transcriptome Signature of Immature and In Vitro-Matured Equine Cumulus-Oocytes Complex.International journal of molecular sciences · 2023Article
- Biallelic variants ineLife · 2023Article
- LSM14B is an Oocyte-Specific RNA-Binding Protein Indispensable for Maternal mRNA Metabolism and Oocyte Development in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Regulation of oocyte maturation: Role of conserved ERK signaling.Molecular reproduction and development · 2022Review
- Oocyte maturation abnormalities - A systematic review of the evidence and mechanisms in a rare but difficult to manage fertility pheneomina.Turkish journal of obstetrics and gynecology · 2022Article
- Oocyte phenotype, genetic diagnosis, and clinical outcome in case of patients with oocyte maturation arrest.Frontiers in endocrinology · 2022Article
- Inhibition of Phosphodiesterase 3A by Cilostazol Dampens Proinflammatory Platelet Functions.Cells · 2021Article
- Modulation of Cyclic AMP Levels in Fallopian Tube Cells by Natural and Environmental Estrogens.Cells · 2021Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Since cAMP blocks meiotic maturation of mammalian and amphibian oocytes in vitro and cyclic nucleotide phosphodiesterase 3A (PDE3A) is primarily responsible for oocyte cAMP hydrolysis, we generated PDE3A-deficient mice by homologous recombination. The Pde3a(-/-) females were viable and ovulated a normal number of oocytes but were completely infertile, because ovulated oocytes were arrested at the germinal vesicle stage and, therefore, could not be fertilized. Pde3a(-/-) oocytes lacked cAMP-specific PDE activity, contained increased cAMP levels, and failed to undergo spontaneous maturation in vitro (up to 48 hours). Meiotic maturation in Pde3a(-/-) oocytes was restored by inhibiting protein kinase A (PKA) with adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS) or by injection of protein kinase inhibitor peptide (PKI) or mRNA coding for phosphatase CDC25, which confirms that increased cAMP-PKA signaling is responsible for the meiotic blockade. Pde3a(-/-) oocytes that underwent germinal vesicle breakdown showed activation of MPF and MAPK, completed the first meiotic division extruding a polar body, and became competent for fertilization by spermatozoa. We believe that these findings provide the first genetic evidence indicating that resumption of meiosis in vivo and in vitro requires PDE3A activity. Pde3a(-/-) mice represent an in vivo model where meiotic maturation and ovulation are dissociated, which underscores inhibition of oocyte maturation as a potential strategy for contraception.
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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.