Pregestational diabetes alters cardiac structure and function of neonatal rats through developmental plasticity

Area of Science:

• Developmental Biology
• Cardiovascular Research
• Endocrinology

Background:

• Pregestational diabetes (PGDM) adversely affects fetal development, particularly cardiac function.
• Maternal hyperglycemia induces cardiac plasticity, including electrical and structural remodeling in offspring.
• The precise molecular mechanisms underlying PGDM-induced cardiac developmental defects remain largely unknown.

Purpose of the Study:

• To elucidate the molecular basis of cardiac developmental defects in neonatal rats from mothers with pregestational diabetes.
• To identify specific molecular pathways and cellular events perturbed in the neonatal heart under hyperglycemic conditions.

Main Methods:

• Induction of pregestational diabetes in female rats using streptozotocin.
• Breeding diabetic female rats with healthy male rats.
• Transcriptomic profiling (RNA-seq) and histopathology of neonatal rat hearts.

Main Results:

• Neonates from diabetic mothers exhibited altered electrocardiography and echocardiography parameters.
• Transcriptomic analysis revealed significant changes in genes related to heart development, fibrosis, conduction, and proliferation.
• Histopathology confirmed focal cardiac fibrosis and increased cell proliferation in affected neonates.

Conclusions:

• Pregestational diabetes perturbs critical molecular pathways and cellular events during neonatal heart development.
• These perturbations contribute to cardiac anomalies and functional deficits observed in offspring of diabetic mothers.
• The study provides a comprehensive molecular map of cardiac developmental plasticity alterations in response to maternal hyperglycemia.