Fetoplacental endothelial dysfunction in gestational diabetes mellitus and maternal obesity: A potential threat for programming cardiovascular disease

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Journal Year: 2023, Volume and Issue: 1869(8), P. 166834 - 166834

Published: Aug. 2, 2023

Gestational diabetes mellitus (GDM) and maternal obesity (MO) increase the risk of adverse fetal outcomes, incidence cardiovascular disease later in life. Extensive research has been conducted to elucidate underlying mechanisms by which GDM MO program offspring disease. This review focuses on role fetoplacental endothelial dysfunction programming for pregnancies. We discuss how pre-existing health conditions can lead vascular unit fetus. also examine impairing system development involvement nitric oxide hydrogen sulfide mediating dysfunction. Furthermore, we suggest that L-Arginine-Nitric Oxide Adenosine-L-Arginine-Nitric (ALANO) signaling pathways are pertinent targets research. Despite significant progress this area, there still knowledge gaps need be addressed future

Language: Английский

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Multigenerational diabetes mellitus

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Gestational diabetes (GDM) changes the maternal metabolic and uterine environment, thus increasing risk of short- long-term adverse outcomes for both mother child. Children mothers who have GDM during their pregnancy are more likely to develop Type 2 Diabetes (T2D), early-onset cardiovascular disease when they themselves become pregnant, perpetuating a multigenerational increased disease. The negative effect is exacerbated by obesity, which induces greater derangement fetal adipogenesis growth. Multiple factors, including genetic, epigenetic metabolic, interact with lifestyle factors contribute development GDM. Genetic particularly important, 30% women having at least one parent T2D. Fetal modifications occur in response GDM, may mediate multi- transgenerational risk. Changes metabolome primarily related fatty acid oxidation, inflammation insulin resistance. These might be effective early biomarkers allowing identification prior hyperglycaemia. impact intra-uterine environment on developing fetus, “developmental programming”, has multisystem effect, but its influence important as it will determine baseline sensitivity, future challenges. Identifying critical window interventions key our ability improve population health.

Language: Английский

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Sex-Specific Alterations in Placental Proteomics Induced by Intrauterine Hyperglycemia

Journal of Proteome Research, Journal Year: 2024, Volume and Issue: 23(4), P. 1272 - 1284

Published: March 12, 2024

Gestational diabetes mellitus (GDM) with intrauterine hyperglycemia induces a series of changes in the placenta, which have adverse effects on both mother and fetus. The aim this study was to investigate placenta GDM its gender differences. In study, we established an model using ICR mice. We collected placental specimens from mice before birth for histological observation, along tandem mass tag (TMT)-labeled proteomic analysis, stratified by sex. When analysis not segregated sex, group showed 208 upregulated 225 downregulated proteins primarily within extracellular matrix mitochondria. Altered biological processes included cholesterol metabolism oxidative stress responses. After stratification male subgroup heightened tendency immune-related pathway alterations, whereas female manifested branched-chain amino acid metabolism. Our suggests that observed sex differences protein expression may explain differential impact offspring.

Language: Английский

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Discrete placental gene expression signatures accompany diabetic disease classifications during pregnancy

American Journal of Obstetrics and Gynecology, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Language: Английский

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Exploring the Diet-Gut Microbiota-Epigenetics Crosstalk Relevant to Neonatal Diabetes

Genes, Journal Year: 2023, Volume and Issue: 14(5), P. 1017 - 1017

Published: April 29, 2023

Neonatal diabetes (NDM) is a rare monogenic disorder that presents as hyperglycemia during the first six months of life. The link between early-life gut microbiota dysbiosis and susceptibility to NDM remains uncertain. Experimental studies have demonstrated gestational mellitus (GDM) could develop into meconium/gut in newborns, thus, it thought be mediator pathogenesis NDM. Epigenetic modifications been considered potential mechanisms by which genes interact with neonatal immune system. Several epigenome-wide association revealed GDM associated cord blood and/or placental DNA methylation alterations. However, linking diet alterations, may turn induce expression linked NDM, are yet unraveled. Therefore, focus this review highlight impacts diet, microbiota, epigenetic crosstalk on altered gene

Language: Английский

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DUSP9-mediated inhibition of IRS1/PI3K/AKT pathway contributes to insulin resistance and metabolic dysfunction in gestational diabetes mellitus

Human Immunology, Journal Year: 2025, Volume and Issue: 86(3), P. 111263 - 111263

Published: Feb. 27, 2025

Language: Английский

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DNA Methylation Signatures in Paired Placenta and Umbilical Cord Samples: Relationship with Maternal Pregestational Body Mass Index and Offspring Metabolic Outcomes

Biomedicines, Journal Year: 2024, Volume and Issue: 12(2), P. 301 - 301

Published: Jan. 27, 2024

An epigenomic approach was used to study the impact of maternal pregestational body mass index (BMI) on placenta and umbilical cord methylomes their potential effect offspring's metabolic phenotype. DNA methylome assessed in 24 paired samples. The differentially methylated CpGs associated with BMI were identified pathways potentially related diseases affected by annotated genes determined. Two top studied 90 additional samples relationship phenotype results showed that is methylation involved endocrine developmental effects type 2 diabetes obesity. expression

Language: Английский

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Overexpression of Tfap2a in Mouse Oocytes Impaired Spindle and Chromosome Organization

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14376 - 14376

Published: Nov. 19, 2022

Transcription factor AP-2-alpha (Tfap2a) is an important sequence-specific DNA-binding protein that can regulate the transcription of multiple genes by collaborating with inducible viral and cellular enhancer elements. In this experiment, expression, localization, functions Tfap2a were investigated in mouse oocytes during maturation. Overexpression via microinjection Myc-Tfap2a mRNA into ooplasm, immunofluorescence, immunoblotting used to study role oocyte meiosis. According our results, plays a vital Levels GV mice suffering from type 2 diabetes increased considerably. was distributed both ooplasm nucleoplasm, its level gradually as meiosis resumption progressed. The overexpression loosened chromatin, accelerated germinal vesicle breakdown (GVBD), blocked first polar body extrusion 14 h after maturation vitro. width metaphase plate at I stage increased, spindle chromosome organization II disrupted overexpressed Tfap2a. Furthermore, dramatically boosted expression p300 oocytes. Additionally, levels pan histone lysine acetylation (Pan Kac), H4 12 (H4K12ac), 16 (H4K16ac), well lactylation Kla), H3 lysine18 (H3K18la), lysine12 (H4K12la), all overexpression. Collectively, upregulated p300, lactylation, impeded assembly alignment, ultimately hindered

Language: Английский

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Epigenetic Responses to Nonchemical Stressors: Potential Molecular Links to Perinatal Health Outcomes

Current Environmental Health Reports, Journal Year: 2024, Volume and Issue: 11(2), P. 145 - 157

Published: April 6, 2024

Language: Английский

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Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity: State of the art and research gaps

Epigenetics, Journal Year: 2022, Volume and Issue: 17(13), P. 2188 - 2208

Published: Aug. 11, 2022

SUMMARYMaternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk the offspring. The placenta, interposed between mother and foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites placental tissue pregnancies complicated by obesity. We reviewed all published original research relevant to topic analysed our findings focus identifying overlaps, contradictions, gaps. Most focused on association gestational hyperglycaemia methylation at term. overlaps results related specific candidate genes, but also observed large gap affected type 1 diabetes. Other unanswered questions relate analysis cell types timing change response during pregnancy. Maternal metabolism altered already first trimester involving structural functional changes into its effects period lacking urgently needed. Foetal sex an important determinant outcome, only few taken account. Collectively, we provide reference work for researchers working evolving field. Based literature review, formulate suggestions future

Language: Английский

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