In vitro hyperglycemia or a diabetic intrauterine environment reduces neonatal endothelial colony-forming cell...

Area of Science:

• Developmental biology
• Endocrinology
• Vascular biology

Background:

• Maternal diabetes is linked to long-term health issues in offspring, including hypertension.
• Circulating endothelial progenitor cells (EPCs) are crucial for vascular repair and disease risk.
• The impact of a diabetic intrauterine environment on neonatal EPC function is not well understood.

Purpose of the Study:

• To investigate whether in vitro hyperglycemia or a diabetic intrauterine environment affects neonatal endothelial progenitor cell (EPC) function.
• To explore the mechanisms underlying potential alterations in EPCs due to maternal diabetes.

Main Methods:

• Utilized clonogenic endothelial colony-forming cell (ECFC) assays to assess EPC function.
• Employed murine transplantation experiments to examine human vasculogenesis in vivo.
• Analyzed ECFC colony formation, self-renewal, capillary-like tube formation, proliferation, and senescence.

Main Results:

• Both in vitro hyperglycemia and a diabetic intrauterine environment significantly reduced ECFC colony formation, self-renewal, and tube formation.
• Impaired ECFC function was associated with premature senescence and reduced proliferation.
• Transplanted ECFCs from diabetic pregnancies formed fewer chimeric vessels compared to controls.

Conclusions:

• Hyperglycemia and a diabetic intrauterine environment diminish neonatal ECFC function both in vitro and in vivo.
• These findings offer mechanistic insights into the increased cardiovascular complication risk in offspring of diabetic pregnancies.
• Altered neonatal EPC function may contribute to the long-term vascular health consequences observed in these children.