ArticleAmerican journal of obstetrics and gynecology2015
Oxidative stress is responsible for maternal diabetes-impaired transforming growth factor beta signaling in the developing mouse heart.
Article in American journal of obstetrics and gynecology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 49 citations in OpenAlex.
- The Impact of Maternal Obesity and Diabetes on the Development of Congenital Heart Defects (CHDs) in Offspring: A Narrative Review.Metabolites · 2026Review
- Oxidative stress in pediatric diseases associated with the origin of life and growth and development.Frontiers in cell and developmental biology · 2025Review
- Impact of genetic factors on antioxidant rescue of maternal diabetes-associated congenital heart disease.JCI insight · 2024Article
- The Effect of Oxidative Stress and Antioxidants Treatment on Gestational Diabetes Mellitus Outcome: A Scoping Review.Cell biochemistry and biophysics · 2024Article
- MicroRNA-322 overexpression reduces neural tube defects in diabetic pregnancies.American journal of obstetrics and gynecology · 2024Article
- Maternal Pre-Existing Diabetes: A Non-Inherited Risk Factor for Congenital Cardiopathies.International journal of molecular sciences · 2023Review
- ER stress and lipid imbalance drive embryonic cardiomyopathy in a human heart organoid model of pregestational diabetes.bioRxiv : the preprint server for biology · 2023Article
- Impact of maternal hyperglycemia on cardiac development: Insights from animal models.Genesis (New York, N.Y. : 2000) · 2021Review
- The role of glucose in physiological and pathological heart formation.Developmental biology · 2021Review
- Using Innovative Machine Learning Methods to Screen and Identify Predictors of Congenital Heart Diseases.Frontiers in cardiovascular medicine · 2021Article
- Deficiency of the oxidative stress-responsive kinase p70S6K1 restores autophagy and ameliorates neural tube defects in diabetic embryopathy.American journal of obstetrics and gynecology · 2020Article
- Gene-by-gene interactions associated with the risk of conotruncal heart defects.Molecular genetics & genomic medicine · 2020Article
- Say NO to ROS: Their Roles in Embryonic Heart Development and Pathogenesis of Congenital Heart Defects in Maternal Diabetes.Antioxidants (Basel, Switzerland) · 2019Review
- Fetal hypoxia and hyperglycemia in the formation of phenytoin-induced cleft lip and maxillary hypoplasia.Epilepsia open · 2019Article
- The increased activity of a transcription factor inhibits autophagy in diabetic embryopathy.American journal of obstetrics and gynecology · 2019Article
- Maternal hyperglycemia and fetal cardiac development: Clinical impact and underlying mechanisms.Birth defects research · 2018Review
- High Glucose Inhibits Neural Stem Cell Differentiation Through Oxidative Stress and Endoplasmic Reticulum Stress.Stem cells and development · 2018Article
- Identification and Evolution of TGF-β Signaling Pathway Members in Twenty-Four Animal Species and Expression in Tilapia.International journal of molecular sciences · 2018Article
- Oxidative stress-induced miR-27a targets the redox gene nuclear factor erythroid 2-related factor 2 in diabetic embryopathy.American journal of obstetrics and gynecology · 2018Article
- The current status and future of cardiac stem/progenitor cell therapy for congenital heart defects from diabetic pregnancy.Pediatric research · 2018Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveOxidative stress plays a causal role in diabetic embryopathy. Maternal diabetes induces heart defects and impaired transforming growth factor beta (TGFβ) signaling, which is essential for cardiogenesis. We hypothesize that mitigating oxidative stress through superoxide dismutase 1 (SOD1) overexpression in transgenic (Tg) mice reverses maternal hyperglycemia-impaired TGFβ signaling and its downstream effectors. STUDY
designDay 12.5 embryonic hearts from wild-type (WT) and SOD1 overexpressing embryos of nondiabetic (ND) and diabetic mellitus (DM) dams were used for the detection of oxidative stress markers: 4-hydroxynonenal (4-HNE) and malondlaldehyde (MDA), and TGFβ1, 2, and 3, phosphor (p)-TGFβ receptor II (TβRII), p-phosphorylated mothers against decapentaplegic (Smad)2, and p-Smad3. The expression of 3 TGFβ-responsive genes was also assessed. Day 11.5 embryonic hearts were explanted and cultured ex vivo, with or without treatments of a SOD1 mimetic (Tempol; Enzo Life Science, Farmingdale, NY) or a TGFβ recombinant protein for the detection of TGFβ signaling intermediates.
resultsLevels of 4-HNE and MDA were significantly increased by maternal diabetes, and SOD1 overexpression blocked the increase of these 2 oxidative stress markers. Maternal diabetes suppresses the TGFβ signaling pathway by down-regulating TGFβ1 and TGFβ3 expression. Consequently, phosphorylation of TβRII, Smad2, and Smad3, downstream effectors of TGFβ, and expression of 3 TGFβ-responsive genes were reduced by maternal diabetes, and these reductions were prevented by SOD1 overexpression. Treatment with Tempol or TGFβ recombinant protein restored high-glucose-suppressed TGFβ signaling intermediates and responsive gene expression.
conclusionOxidative stress mediates the inhibitory effect of hyperglycemia in the developing heart. Antioxidants, TGFβ recombinant proteins, or TGFβ agonists may have potential therapeutic values in the prevention of heart defects in diabetic pregnancies.
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