Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia

Abstract

This study explores the molecular composition of the tight junction (TJ) in human term placenta from normal women and from patients with preeclampsia, a hypertensive disorder of pregnancy. Maternal endothelial dysfunction is a critical characteristic of preeclampsia; hence, we have analyzed its impact on placental vessels. The study concentrates on the TJ because this structure regulates the sealing of the paracellular route. We have found that, in placental endothelial vessels, TJ components include the peripheral protein ZO-1 and the integral proteins occludin and claudins 1, 3, and 5. During preeclampsia, the amounts of occludin and ZO-1 exhibit no significant variation, whereas those of claudins 1, 3, and 5 diminish, suggesting the presence of leakier TJs in the endothelia of the preeclamptic placenta, possibly in response to the decreased perfusion of this organ during preeclampsia. We have unexpectedly found that, in normal placentae, the multinucleated syncytiotrophoblast layer displays claudin 4 at the basal surface of the plasma membrane, and claudin 16 along the apical and basolateral surfaces. The presence of membrane-lined channels that cross the syncytiotrophoblast constituting a paracellular pathway has been determined by transmission electron microscopy and by the co-immunolocalization of claudin 16 with the plasma membrane proteins Na+K+-ATPase and GP135. Since claudin 16 functions as a paracellular channel for Mg2+, its diffuse pattern in preeclamptic placentae suggests the altered paracellular transport of Mg2+ between the maternal blood and the placental tissue.

A survey of zeb1, twist and claudin 1 and 4 expression during placental development and disease

“…Claudins are tight junctional molecules, which are present in epithelial, endothelial and mesothelial cells (21,23,43). Claudin 1 and 4 are commonly found in epithelial cells and claudins 1, 3 and 5 have been detected in endothelial cells of term placenta (44). However, in that paper, the expression of claudin was not evaluated in the earlier trimesters.…”

Gene expression in chorionic villous samples at 11 weeks of gestation in women who develop preeclampsia later in pregnancy: implications for screening

“…Claudins are essential components of the intercellular tight junction (TJ). Endothelia of the terminal villi display diminished expression of TJ proteins in case of PE (Liévano et al, 2006) and, accordingly, the effect of PE upon endothelial TJ proteins is a significant decreased expression of claudins (Leach et al, 2000(Leach et al, , 2002. This diminished expression might generate TJs that allow a less restrictive passage of molecules through the paracellular pathway and might arise in the placenta as a consequence of hypertension experienced by the preeclamptic mother in whom an increase in interstitial fluid is thought to be attributable to the capillary leakage of fluid and proteins.…”

Comparison of human uterine cervical electrical impedance measurements derived using two tetrapolar probes of different sizes

“…One study in mice has shown that the increase in the expression of the glycosaminoglycan hyaluron which is associated with cervical prelabour ripening not only occurs in the cervical stroma but also, to a lesser extent, in the epithelium[15]. Studies of human and animal epithelial tissue have highlighted the physiological role of gap junctional proteins such as occludin and the claudins in modulating cell contact and permeability [16-19]. Little is known of the epithelial changes associated with human cervical preparation for birth and changes in these gap junctional proteins have not been described in the cervix during human pregnancy.…”