Endothelial-to-mesenchymal transition in the fetoplacental macrovasculature and microvasculature in pregnancies complicated by gestational diabetes
Author(s)
Type
Journal Article
Abstract
Gestational diabetes mellitus (GDM) is linked to altered fetal development and an increased risk of offspring developing cardiometabolic diseases in adulthood. The mechanisms responsible are unclear; however, GDM is associated with altered fetoplacental vascularisation, fibrosis and endothelial dysfunction. In non-pregnant individuals with diabetes, similar vascular changes are attributed to disruptions in endothelial-to-mesenchymal transition (EndMT), a key process where endothelial cells adopt a mesenchymal phenotype. Here, we assess whether alterations in the fetoplacental macro- and microvasculature are attributed to EndMT, using human umbilical vein endothelial cells (HUVECs) and human term placental tissue, respectively. Transforming growth factor (TGF)-β2 and interleukin (IL)-1β induced morphological and molecular changes consistent with EndMT in both GDM and non-GDM HUVECs. The ability of TGF-β2 and IL-1β to alter expression of known EndMT regulators, VWF, TGFBR1, IL1B and IL1R1, was diminished in GDM HUVECs; however, all other hallmarks of EndMT were similar. In placental villous tissue, Slug and Snail, two key transcriptional regulators of EndMT, were detected in the villous stroma, suggesting that EndMT probably occurs in the placental microvasculature. We observed a reduction in endothelial marker genes PECAM1, VWF and CDH5 in GDM placentas, suggesting reduced placental vascularisation. This was accompanied by a reduction in EndMT regulators SNAI2, TGB2, TGFB3 and TGFBR2; however, there was no change in mesenchymal markers or other EndMT regulators. This suggests that there may be some alterations in EndMT in GDM but this probably does not fully explain the endothelial dysfunction and altered vascularisation that occurs in the fetoplacental vasculature in pregnancies complicated by GDM.
Date Issued
2026-06-01
Date Acceptance
2025-05-01
Citation
Journal of Physiology, 2026, 604 (11), pp.4405-4425
ISSN
0022-3751
Publisher
Wiley
Start Page
4405
End Page
4425
Journal / Book Title
Journal of Physiology
Volume
604
Issue
11
Copyright Statement
© 2025 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40349322
Subjects
ANGIOGENESIS
CELLS
DISEASE
endothelial-to-mesenchymal transition
fetoplacental endothelium
GDM
gestational diabetes mellitus
HYPERGLYCEMIA
Life Sciences & Biomedicine
macrovasculature
MELLITUS
microvasculature
Neurosciences
Neurosciences & Neurology
OSTEOGENIC DIFFERENTIATION
Physiology
placenta
Science & Technology
TYPE-1
umbilical cord
VASCULOGENESIS
VESSELS
WOMEN
Publication Status
Published
Coverage Spatial
England
Date Publish Online
2025-05-11