["The Journal of Physiology, Volume 604, Issue 11, Page 4405-4425, 1 June 2026. ", "\nAbstract figure legend Transforming growth factor (TGF)‐β2 and interleukin (IL)‐1β induced morphological and molecular changes consistent with endothelial‐to‐mesenchymal transition (EndMT) in HUVECs isolated from both pregnancies complicated by gestational diabetes (GDM) and non‐GDM pregnancies. In HUVECs from GDM pregnancies, Cadherin‐5/VE‐cadherin (CDH5) was increased. Whilst the ability of TGF‐β2 and IL‐1β to alter expression of transforming growth factor‐beta receptor type 1 (TGFBR1) was diminished in GDM HUVECs, all other hallmarks of EndMT were similar. EndMT markers and mediators were expressed in human placental villous tissue. Endothelial marker genes, Platelet endothelial cell adhesion molecule (PECAM1), von Willebrand factor (VWF) and CDH5 were reduced in GDM placentas. This was accompanied by a reduction in EndMT regulators, Snail Family Transcriptional Repressor 2 (SNAI2/Slug), transforming growth factor beta‐2 (TGFB2), transforming growth factor beta‐3 (TGFB3) and transforming growth factor‐beta receptor type 2 (TGFBR2); however, there was no change in mesenchymal markers or other EndMT regulators.\n\n\n\n\nAbstract\nGestational 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.\n\n\n\n\n\n\n\n\n\nKey points\n\nGestational diabetes mellitus (GDM) has been linked to altered placental vascularisation, fibrosis and endothelial dysfunction.\nDisruptions in endothelial‐to‐mesenchymal transition (EndMT), a process where endothelial cells adopt a mesenchymal phenotype, has been linked to vascular complications in diabetes, but EndMT in GDM has not been investigated.\nTransforming growth factor (TGF)‐β2 and interleukin (IL)‐1β induced morphological and molecular changes consistent with EndMT in GDM and non‐GDM human umbilical vein endothelial cells (HUVECs). Although the expression of EndMT mediators, VWF, TGFBR1, IL1B, and IL1R1, was diminished in GDM HUVECs, other EndMT hallmarks were similar.\nTranscriptional regulators of EndMT, Slug and Snail, were detected in the human term placenta. Despite a reduction in endothelial markers, PECAM1, VWF and CDH5, as well as SNAI2, TGFB2/3 and TGFBR2 in GDM placenta, there was no change in mesenchymal or other EndMT markers.\nThis suggests that, although there may be some changes to EndMT in GDM, the vascular dysfunction is probably not explained fully by alterations in EndMT.\n\n\n"]