ArticleMolecular human reproduction2015
A role for retinoids in human oocyte fertilization: regulation of connexin 43 by retinoic acid in cumulus granulosa cells.
Article in Molecular human reproduction, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Article
- Changes in gene expression associated with vitamin A metabolism in the corpora lutea and endometria during d 15 of the estrous cycle and throughout gestation in gilts.Journal of animal science · 2026Article
- Targeting Multidrug Resistance in Cancer: Impact of Retinoids, Rexinoids, and Carotenoids on ABC Transporters.International journal of molecular sciences · 2025Review
- Porcine granulosa cell transcriptomic analyses reveal the differential regulation of lncRNAs and mRNAs in response to all-trans retinoic acid in vitro.Animal bioscience · 2025Article
- Vitamins, Coenzyme Q10, and Antioxidant Strategies to Improve Oocyte Quality in Women with Gynecological Cancers: A Comprehensive Review.Antioxidants (Basel, Switzerland) · 2024Review
- Current Status of Ovarian and Endometrial Biomarkers in Predicting ART Outcomes.Journal of clinical medicine · 2024Review
- Retinoic Acid Action in Cumulus Cells: Implications for Oocyte Development and In Vitro Fertilization.International journal of molecular sciences · 2024Article
- Effects of reactive oxygen species and mitochondrial dysfunction on reproductive aging.Frontiers in cell and developmental biology · 2024Review
- Review
- Role of Granulosa Cells in the Aging Ovarian Landscape: A Focus on Mitochondrial and Metabolic Function.Frontiers in physiology · 2021Review
- Clinical Application of Antioxidants to Improve Human Oocyte Mitochondrial Function: A Review.Antioxidants (Basel, Switzerland) · 2020Review
- Newly Identified Regulators of Ovarian Folliculogenesis and Ovulation.International journal of molecular sciences · 2020Review
- Alternatively Activated Macrophages Are the Primary Retinoic Acid-Producing Cells in Human Decidua.Reproductive sciences (Thousand Oaks, Calif.) · 2020Article
- Retinoic acid signaling in ovarian folliculogenesis and steroidogenesis.Reproductive toxicology (Elmsford, N.Y.) · 2019Review
- Effects of all-trans retinoic acid on the in vitro maturation of camel (Camelus dromedarius) cumulus-oocyte complexes.The Journal of reproduction and development · 2019Article
- Retinoic acid improves maturation rate and upregulates the expression of antioxidant-related genes inInternational journal of veterinary science and medicine · 2018Article
- Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Retinoids are essential for ovarian steroid production and oocyte maturation in mammals. Oocyte competency is known to positively correlate with efficient gap junction intercellular communication (GJIC) among granulosa cells in the cumulus-oocyte complex. Connexin 43 (C x 43) is the main subunit of gap junction channels in human cumulus granulosa cells (CGC) and is regulated by all-trans retinoic acid (ATRA) in other hormone responsive cell types. The objectives of this study were to quantify retinoid levels in human CGC obtained during IVF oocyte retrievals, to investigate the potential relationship between CGC ATRA levels and successful oocyte fertilization, and to determine the effects of ATRA on C x 43 protein expression in CGC. Results showed that CGC cultures actively metabolize retinol to produce ATRA. Grouped according to fertilization rate tertiles, mean ATRA levels were 2-fold higher in pooled CGC from women in the highest versus the lowest tertile (P < 0.05). ATRA induced a rapid dephosphorylation of C x 43 in CGC and granulosa cell line (KGN) cultures resulting in a >2-fold increase in the expression of the functional non-phosphorylated (P0) species (P < 0.02). Similar enhancement of P0 by ATRA was shown in CGC and KGN cultures co-treated with LH or hCG which, by themselves, enhanced the protein levels of C x 43 without altering its phosphorylation profile. Correspondingly, the combination of ATRA+hCG treatment of KGN caused a significant increase in GJIC compared with single agent treatments (P < 0.025) and a doubling of GJIC from that seen in untreated cells (P < 0.01). These findings indicate that CGC are a primary site of retinoid uptake and ATRA biosynthesis. Regulation of C x 43 by ATRA may serve an important role in folliculogenesis, development of oocyte competency, and successful fertilization by increasing GJIC in CGC.
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