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Impaired Angiogenic Function of Fetal Endothelial Progenitor Cells via PCDH10 in Gestational Diabetes Mellitus

Hayan Kwon1, Yun Ji Jung1, Yeji Lee1

  • 1Department of Obstetrics and Gynecology, Institute of Women's Life Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

International Journal of Molecular Sciences
|November 25, 2023
PubMed

Insights

Gestational diabetes mellitus (GDM) in mothers impairs fetal endothelial progenitor cells (EPCs), increasing offspring cardiovascular disease risk. This occurs via altered gene expression and epigenetic changes in fetal EPCs due to in utero hyperglycemia.

Area of Science:

  • Cardiovascular Science
  • Developmental Biology
  • Epigenetics

Background:

  • Maternal hyperglycemia from gestational diabetes mellitus (GDM) negatively impacts fetal vascular development.
  • This increases offspring cardiovascular disease (CVD) risk.
  • Mechanisms involving fetal endothelial progenitor cells (EPCs) are not fully understood.

Purpose of the Study:

  • To investigate the effects of intrauterine hyperglycemia on fetal EPC function and epigenetic modifications.
  • To identify specific molecular mechanisms linking GDM to impaired fetal vascular development.

Main Methods:

  • Functional assays of outgrowth endothelial cells (OECs) derived from GDM pregnancies (GDM-EPCs).
  • Analysis of PCDH10 gene expression and its promoter methylation status in GDM-EPCs.
  • Correlation of angiogenic function with gene expression and epigenetic changes.

Main Results:

  • Intrauterine hyperglycemia impairs the angiogenic function of fetal EPCs.
  • PCDH10 expression is elevated in GDM-EPCs, correlating with inhibited angiogenic function.
  • Increased PCDH10 expression is linked to hypomethylation of its promoter.

Conclusions:

  • In utero GDM exposure induces angiogenic dysfunction in fetal EPCs.
  • Altered gene expression (PCDH10) and epigenetic changes (hypomethylation) are key mechanisms.
  • This dysfunction increases offspring susceptibility to cardiovascular diseases.

Keywords:
PCDH10angiogenesisendothelial progenitor cellsepigenetic changesgestational diabetes mellitus

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