Role of Maternal Obesity in Offspring Cardiovascular Development and Congenital Heart Defects

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Май 2, 2025

Background Congenital heart disease is a leading cause of death in newborns, yet many its molecular mechanisms remain unknown. Both maternal obesity and diabetes increase the risk congenital offspring, with recent studies suggesting these conditions may have distinct teratogenic mechanisms. The global prevalence rising, while known factor for fetal disease, specific are largely unexplored. Methods Results We used murine model diet‐induced obesity, without diabetes, to produce dams that were overweight but had normal blood glucose levels. Embryos generated their developing hearts analyzed. Transcriptome analysis was performed using single‐nucleus bulk RNA sequencing. Global phospho‐enriched proteome tandem mass tag–mass spectroscopy. Immunobloting histologic evaluation also performed. Analysis revealed disrupted oxidative phosphorylation reactive oxygen species formation, reduced antioxidant capacity, evidenced by downregulation genes Sod1 Gp4x , Hif1a signaling. Evidence stress, cell signaling, alteration Rho GTPase actin cytoskeleton signaling observed. Genes involved cardiac morphogenesis, including Hand2 downregulated, fewer mature cardiomyocytes present. Histologic confirmed increased defects embryos exposed obesity. Conclusions These findings demonstrate alone can result through similar those associated hyperglycemia. This study provides valuable insight into role growing modifiable factor, development most common birth defect, disease.

Язык: Английский

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Circular RNAs mediate the regulation of maternal placental nutrient transport and fetal development by sugar-sweetened beverages

Food Research International, Год журнала: 2024, Номер 193, С. 114856 - 114856

Опубликована: Июль 30, 2024

Язык: Английский

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Placental Bioenergetics and Antioxidant Homeostasis in Maternal Obesity and Gestational Diabetes

Antioxidants, Год журнала: 2024, Номер 13(7), С. 858 - 858

Опубликована: Июль 18, 2024

Maternal obesity has been associated with short- and long-term risks of pregnancy-perinatal adverse events, possibly due to alterations placental mitochondrial bioenergetics. However, several detrimental mechanisms occurring in the placentas women still need be clarified. Here, we analyzed features oxidative environment 46 pregnancies relation pre-pregnancy BMI. Seventeen Caucasian normal-weight (NW) twenty-nine who were obese (OB) enrolled. The protein expression CypD electron transfer chain complexes (C) I–V measured, as well ATP production oxygen consumption rates (OCRs). levels pro/anti-oxidant enzymes TXNIP, SOD2, PON2 also analyzed. Despite no differences expression, OCRs significantly lower OB vs. NW women. Accordingly, synthase (CV) content decreased women, positively correlating efficiency, suggesting a link between deficiency dysfunction. SOD2 negatively correlated maternal BMI, indicating possible impairment antioxidant defenses increasing These changes worsened 10 presenting gestational diabetes mellitus. Overall, these results suggest bioenergetics obesity, leading dysfunction altered fetal development programming.

Язык: Английский

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Decoding human placental cellular and molecular responses to maternal obesity and fetal growth

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Янв. 28, 2025

Abstract Obesity poses risks to maternal health and increases the likelihood of short– long-term adverse pregnancy outcomes in offspring. The placenta, a key organ at maternal-fetal interface, responds obesity regulates fetal growth. To investigate molecular features physiological adaptation, we perform single-nuclei RNA-seq on human placentas compared transcriptomic profiles women with delivering appropriate-or large-for-gestational age (i.e., AGA LGA) babies those from normal-weight healthy controls babies. Commonness-score metric is developed identify responses attributable effects or We find hypoxia induction TNF-α signaling syncytiotrophoblasts, while receptor tyrosine kinases are down-regulated cytotrophoblasts irrespective Notably, that fine-tune PI3K-AKT MAPK cascade pathways underlies versus LGA. Hofbauer cells upregulate immunometabolic genes specifically LGA also express most ligands detected only Finally, use novel microfluidic organs-on-a-chip device fabricated for co-culturing adipose spheroids trophoblast organoids. This system recapitulates some syncytiotrophoblasts obesity, offering functionally relevant reductionistic study maternal-placental interaction. Our findings deconvolute cellular adaptation placenta overgrowth condition.

Язык: Английский

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Semaglutide ameliorates metabolic disorders in offspring via regulation of oocyte ROS of pre-pregnancy obesity mice

Acta Pharmacologica Sinica, Год журнала: 2025, Номер unknown

Опубликована: Фев. 21, 2025

Язык: Английский

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Effects of fermented wheat germ on the placenta of high-fat diet-induced obese maternal rats: morphology, metabolism, and nutrient transport

Food & Function, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Fermented wheat germ improved morphology, alleviated metabolic disorders, and regulated nutrient transport of placenta in maternal rats with obesity induced by a high-fat diet.

Язык: Английский

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Aromatics from fossil fuels and breast cancer

iScience, Год журнала: 2025, Номер unknown, С. 112204 - 112204

Опубликована: Март 1, 2025

Polycyclic aromatic hydrocarbons (PAHs) from fossil fuels initiate breast cancer in animal models, and humans a link between PAH exposure risk has been established. In women, it takes approximately two decades for PAH-exposed cells to progress diagnosable cancer, the needs happen during time window when is vulnerable PAHs. Further, not everyone exposed high levels of PAHs develops cancer. are most likely lead initiation among individuals who were utero through pregnant mothers environmental pollutants or maternal obesity both. These early life exposures shown increase daughter's later susceptibility by causing daughter (1) an number structures which place, (2) suppression, perhaps epigenetically, ability repair DNA damage caused inhibiting expression tumor suppressor genes, (3) persistent gut dysbiosis, then impacts immune microenvironment. Among that may be volatile BTEX compounds. Thus, aromatics involved efforts should directed toward reducing human these compounds prevent

Язык: Английский

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Effect of maternal body mass index on inflammatory biomarkers and dynamic thiol-disulfide homeostasis during pregnancy

BMC Pregnancy and Childbirth, Год журнала: 2025, Номер 25(1)

Опубликована: Март 13, 2025

The aim of this study was to investigate the relationship between maternal body mass index (BMI), a modifiable factor during reproductive period, and inflammation oxidative stress by assessing dynamic thiol-disulfide homeostasis (TDH) in both mother fetus. This prospective cohort conducted May June 2024 at tertiary obstetric care center. inclusion criteria consisted healthy pregnant women aged over 18 years, 37 41 weeks gestation, who had not used medications other than iron folic acid supplements, with newborns birth weight 2,500 grams (g) 4,500 g, Apgar scores ≥ 7 5th minute after birth. Maternal peripheral blood (5 mL) collected delivery admission, 3 mL fetal obtained from umbilical cord delivery. Participants (n = 125) were categorized into three BMI-based groups: (1) non-obese pre-pregnancy (BMI < 30 kg/m², n 72); (2) but gained BMI classified as obese kg/m² pre-pregnancy, delivery, 29); (3) 24). serum native thiol (SH) (306.21 ± 49.19 µmol/L vs. 270.9 60.12 276.9 59.18 µmol/L, p 0.004) total (SH + SS) (337.88 52.43 303.8 62.13 306 58.01 0.006) levels significantly higher group compared groups. Disulfide (SS) ratios (SS/SH, SS/total thiol, SH/total thiol) showed no significant differences among groups (p > 0.05, for all). In blood, SH, SS, SH SS levels, different obesity, whether longstanding or newly developed pregnancy, disrupts TDH reduces antioxidant capacity, increasing susceptibility damage may affect health. Not applicable.

Язык: Английский

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Oxidative Stress in Maternal and Offspring Kidney Disease and Hypertension: A Life-Course Perspective

Antioxidants, Год журнала: 2025, Номер 14(4), С. 387 - 387

Опубликована: Март 26, 2025

Kidney disease and hypertension are interconnected, prevalent conditions that affect both pregnant women children. Oxidative stress occurs when reactive oxygen species or nitrogen exceed the capacity of antioxidant systems. It plays a critical role in kidney development, resulting programming increased risks for across life course. Animal models have significantly advanced our understanding oxidative stress-related programming, molecular mechanisms involved, early-life interventions to prevent disease. This review critically examines influence perinatal on highlighting its long-term effects outcomes susceptibility hypertension. also explores potential antioxidant-based preventing Furthermore, addresses existing gap between insights gained from animal their translation into clinical practices, emphasizing challenges opportunities future research this area.

Язык: Английский

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Psychosocial stress and associations with inflammation in mid-gestation maternal, fetal, and placental tissue

Reproductive Toxicology, Год журнала: 2025, Номер unknown, С. 108922 - 108922

Опубликована: Апрель 1, 2025

Язык: Английский

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