Blue, Emily K.DiGiuseppe, RobertDerr-Yellin, EthelAcosta, Juan CarlosPay, S. LouiseHanenberg, HelmutSchellinger, Megan M.Quinney, Sara K.Mund, Julie A.Case, JamieHaneline, Laura S.2025-04-282025-04-282014Blue EK, DiGiuseppe R, Derr-Yellin E, et al. Gestational diabetes induces alterations in the function of neonatal endothelial colony-forming cells. Pediatr Res. 2014;75(2):266-272. doi:10.1038/pr.2013.224https://hdl.handle.net/1805/47493Background: Children born to mothers with gestational diabetes mellitus (GDM) experience increased risk of developing hypertension, type 2 diabetes mellitus, and obesity. Disrupted function of endothelial colony-forming cells (ECFCs) may contribute to this enhanced risk. The goal of this study was to determine whether cord blood ECFCs from GDM pregnancies exhibit altered functionality. Methods: ECFCs isolated from the cord blood of control and GDM pregnancies were assessed for proliferation, senescence, and Matrigel network formation. The requirement for p38MAPK in hyperglycemia-induced senescence was determined using inhibition and overexpression studies. Results: GDM-exposed ECFCs were more proliferative than control ECFCs. However, GDM-exposed ECFCs exhibited decreased network-forming ability in Matrigel. Aging of ECFCs by serial passaging led to increased senescence and reduced proliferation of GDM-exposed ECFCs. ECFCs from GDM pregnancies were resistant to hyperglycemia-induced senescence compared with those from controls. In response to hyperglycemia, control ECFCs activated p38MAPK, which was required for hyperglycemia-induced senescence. In contrast, GDM-exposed ECFCs showed no change in p38MAPK activation under equivalent conditions. Conclusion: Intrauterine exposure of ECFCs to GDM induces unique phenotypic alterations. The resistance of GDM-exposed ECFCs to hyperglycemia-induced senescence and decreased p38MAPK activation suggest that these progenitor cells have undergone changes that induce tolerance to a hyperglycemic environment.en-USPublisher PolicyCollagenFetal bloodHyperglycemiaEndothelial cellsArticle