Effects of gestational diabetes on junctional adhesion molecules in human term placental vasculature

Aims/hypothesis. The aim of this study was to investigate whether gestation al diabetes mellitus, which occurs in the microvascular remodelling phase o f 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 norma l pregnancy (n = 5) and those complicated by gestational diabetes (n = 5) w ere perfusion-fixed and analysed by indirect immunofluorescence and confoca l scanning microscopy. Using systematic random sampling, the surface expres sion of endothelial junctional proteins and the relative incidences of immu nostained vessels were compared between the two study groups. Total vessel lengths were measured by stereological techniques. Results. The adherens junctional molecules, vascular-endothelial cadherin a nd beta-catenin, and the tight junctional molecules, occludin and zonula oc cludens-1 were localised to paracellular clefts in both study groups. The d iabetic placentae showed pronounced reductions in the intensity of immunofl uorescence and in the number of immune-positive vessels. A corresponding st atistically significant increase (from 19% to 56%) in the percentage of ves sels showing junctional anti-phosphotyrosine immunoreactivity was found. Th e differences observed represented real changes in the absolute lengths of immunostained regions along the vessels. The stereological measurements fai led to detect any statistically significant change in the combined length o f fetal vessels in gestational diabetic placenta. Conclusion/interpretation. Our results suggest that even short duration dia betic insult, alters the surface expression of placental junctional protein s. This alteration could be mediated by the tyrosine-phosphorylation pathwa y. The changes suggest impaired barrier function rather than accelerated va scular growth.