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

Area of Science:

• Developmental Biology
• Cardiovascular Research
• Metabolic Disorders

Background:

• Congenital heart disease (CHD) is a major cause of infant mortality, with unknown molecular underpinnings.
• Maternal obesity and diabetes are known risk factors for CHD, potentially acting through distinct mechanisms.
• Rising global obesity rates necessitate understanding maternal obesity's impact on fetal heart development.

Purpose of the Study:

• To investigate the molecular mechanisms by which maternal obesity, independent of diabetes, leads to congenital heart defects.
• To identify specific pathways affected by maternal obesity during embryonic heart development.

Main Methods:

• Utilized a murine model of diet-induced maternal obesity without diabetes.
• Performed single-nucleus and bulk RNA sequencing for transcriptome analysis.
• Conducted proteome analysis, immunoblotting, and histological evaluation of embryonic hearts.

Main Results:

• Maternal obesity disrupted oxidative phosphorylation, increased reactive oxygen species, and reduced antioxidant capacity (e.g., downregulation of Sod1, Gp4x).
• Observed evidence of oxidative stress, cell death signaling, and altered Rho GTPase/actin cytoskeleton pathways.
• Downregulation of cardiac morphogenesis genes (e.g., Hand2) and reduced mature cardiomyocytes were noted, alongside increased cardiac defects.

Conclusions:

• Maternal obesity alone can induce cardiac defects via mechanisms overlapping with maternal hyperglycemia.
• This research provides critical insights into maternal obesity as a modifiable risk factor for CHD.