Endothelia of term human placentae display diminished expression of tight junction proteins during preeclampsia.
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.
Liévano
Samuel
S
Gynecology and Obstetrics Hospital, La Raza Medical Center, Mexican Institute of Social Security (IMSS), México D.F., Mexico.
Alarcón
Lourdes
L
Chávez-Munguía
Bibiana
B
González-Mariscal
Lorenza
L
D000328:Adult; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D057167:Claudins; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D046529:Microscopy, Electron, Transmission; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism*; D010920:Placenta / Q000098:blood supply* / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism / Q000473:pathology*; D011247:Pregnancy; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure*; D014327:Trophoblasts / Q000502:physiology / Q000648:ultrastructure; D062826:Zonula Occludens-1 Protein
C568108:CLDN1 protein, human; C568122:CLDN3 protein, human; C568157:CLDN4 protein, human; C107466:CLDN5 protein, human; D062445:Claudin-1; D062465:Claudin-3; D062506:Claudin-4; D062507:Claudin-5; D057167:Claudins; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; C502010:claudin 16