Byford, A.R., Fakonti, G., Shao, Z. et al. (7 more authors) (2025) Endothelial-to-mesenchymal transition in the fetoplacental macrovasculature and microvasculature in pregnancies complicated by gestational diabetes. The Journal of Physiology. ISSN 0022-3751
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | endothelial-to-mesenchymal transition, fetoplacental endothelium, gestational diabetes mellitus, GDM, macrovasculature, microvasculature, placenta, umbilical cord |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) |
Funding Information: | Funder Grant number MRC (Medical Research Council) MR/R023166/1 MRC (Medical Research Council) Not Known |
Depositing User: | Symplectic Publications |
Date Deposited: | 19 Mar 2025 11:49 |
Last Modified: | 12 Jun 2025 14:03 |
Status: | Published online |
Publisher: | Wiley |
Identification Number: | 10.1113/JP287931 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:224583 |