Effects of gestational diabetes on junctional adhesion molecules in human term placental vasculature.
OBJECTIVE
The aim of this study was to investigate whether gestational diabetes mellitus, which occurs in the microvascular remodelling phase of placental development, causes alterations in surface expression of tight and adherens junctional molecules involved in endothelial barrier function and angiogenesis.


METHODS
Term placenta, delivered by elective Caesarian section, from normal pregnancy (n = 5) and those complicated by gestational diabetes (n = 5) were perfusion-fixed and analysed by indirect immunofluorescence and confocal scanning microscopy. Using systematic random sampling, the surface expression of endothelial junctional proteins and the relative incidences of immunostained vessels were compared between the two study groups. Total vessel lengths were measured by stereological techniques.


RESULTS
The adherens junctional molecules, vascular-endothelial cadherin and beta-catenin, and the tight junctional molecules, occludin and zonula occludens-1 were localised to paracellular clefts in both study groups. The diabetic placentae showed pronounced reductions in the intensity of immunofluorescence and in the number of immuno-positive vessels. A corresponding statistically significant increase (from 19% to 56%) in the percentage of vessels showing junctional anti-phosphotyrosine immunoreactivity was found. The differences observed represented real changes in the absolute lengths of immunostained regions along the vessels. The stereological measurements failed to detect any statistically significant change in the combined length of fetal vessels in gestational diabetic placenta.


CONCLUSIONS
Our results suggest that even short duration diabetic insult, alters the surface expression of placental junctional proteins. This alteration could be mediated by the tyrosine-phosphorylation pathway. The changes suggest impaired barrier function rather than accelerated vascular growth.
Babawale
M O
MO
School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, UK.
Lovat
S
S
Mayhew
T M
TM
Lammiman
M J
MJ
James
D K
DK
Leach
L
L
D015703:Antigens, CD; D001724:Birth Weight; D015820:Cadherins / Q000032:analysis*; D002585:Cesarean Section; D003598:Cytoskeletal Proteins / Q000032:analysis*; D016640:Diabetes, Gestational / Q000188:drug therapy / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology*; D005260:Female; D005865:Gestational Age; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use; D008565:Membrane Proteins / Q000032:analysis; D062793:Occludin; D009929:Organ Size; D010750:Phosphoproteins / Q000032:analysis; D010920:Placenta / Q000033:anatomy & histology* / Q000098:blood supply*; D011247:Pregnancy / Q000502:physiology*; D012016:Reference Values; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D003598:Cytoskeletal Proteins; D006442:Glycated Hemoglobin; D007328:Insulin; D008565:Membrane Proteins; D062793:Occludin; D010750:Phosphoproteins; D015534:Trans-Activators; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D000099152:Cadherin 5; C495270:CTNNB1 protein, human; C568985:OCLN protein, human; C569042:TJP1 protein, human