ArticlePloS one2015
Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- The effect of antenatal corticosteroid use on offspring cardiovascular function: A systematic review.BJOG : an international journal of obstetrics and gynaecology · 2023Pooled it
- Effects of glucocorticoid on cardiac chronotropic responsiveness in cirrhotic rats: A possible role for dopamine receptors.Iranian journal of basic medical sciences · 2026Article
- Childhood systemic glucocorticoid exposure and subsequent alterations in myocardial structure and cardiac function: a narrative review of clinical evidence.Frontiers in endocrinology · 2026Review
- Dose-related cardiac outcomes in response to postnatal dexamethasone treatment in premature lambs.Anatomical record (Hoboken, N.J. : 2007) · 2025Article
- A Dexamethasone-Loaded Polymeric Electrospun Construct as a Tubular Cardiovascular Implant.Polymers · 2023Article
- Unlocking cardiomyocyte renewal potential for myocardial regeneration therapy.Journal of molecular and cellular cardiology · 2023Review
- Impact of Glucocorticoids on Cardiovascular System-The Yin Yang Effect.Journal of personalized medicine · 2022Review
- Glucocorticoid receptor antagonization propels endogenous cardiomyocyte proliferation and cardiac regeneration.Nature cardiovascular research · 2022Article
- Corticosteroid Receptors in Cardiac Health and Disease.Advances in experimental medicine and biology · 2022Article
- Potential Adverse Effects of Dexamethasone Therapy on COVID-19 Patients: Review and Recommendations.Infectious diseases and therapy · 2021Review
- Inhibition of DNA methylation in newborns reprograms ischemia-sensitive biomarkers resulting in development of a heart ischemia-sensitive phenotype late in life.Reproductive toxicology (Elmsford, N.Y.) · 2021Article
- Endocrine Influence on Cardiac Metabolism in Development and Regeneration.Endocrinology · 2021Review
- Effect of Preterm Birth on Cardiac and Cardiomyocyte Growth and the Consequences of Antenatal and Postnatal Glucocorticoid Treatment.Journal of clinical medicine · 2021Review
- Vertebrate cardiac regeneration: evolutionary and developmental perspectives.Cell regeneration (London, England) · 2021Review
- Hormonal control of cardiac regenerative potential.Endocrine connections · 2021Review
- Life Course Impact of Glucocorticoids During Pregnancy on Muscle Development and Function.Frontiers in animal science · 2021Article
- Reawakening the Intrinsic Cardiac Regenerative Potential: Molecular Strategies to Boost Dedifferentiation and Proliferation of Endogenous Cardiomyocytes.Frontiers in cardiovascular medicine · 2021Review
- Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- In vitro and in vivo roles of glucocorticoid and vitamin D receptors in the control of neonatal cardiomyocyte proliferative potential.Journal of molecular and cellular cardiology · 2020Article
- Patient and Disease-Specific Induced Pluripotent Stem Cells for Discovery of Personalized Cardiovascular Drugs and Therapeutics.Pharmacological reviews · 2020Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner.
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