Background:
Preeclampsia is a pregnancy complication which affects 5% of all pregnancies and defined as gestational hypertension and proteinuria. Although the exact cause of preeclampsia remains unclear, there are many studies focus on the relationship between preeclampsia with spiral artery remodeling. Adrenomedullin (ADM) is a peptide belonging to the calcitonin/calcitonin- gene-related peptide (CGRP)/amylin peptide family. In human, plasma ADM level is elevated after implantation and peaks in early pregnancy. The role of ADM in pathology of preeclampsia remains to be demonstrated.
Methodology:The involvement of human subjects in this study was approved by the Institutional Review Board (IRB) of The University of Hong Kong/Hospital Authority Hong Kong West Cluster. To investigate the functions of trophoblast including differentiation, invasion, migration, extravillous trophoblast (EVCT) derived from first trimester villous (gestation 5-12 weeks), term placenta, and chorionic villus samples (CVS) collected from placenta at 10–12 weeks gestation were used.
Results:ADM expression was reduced in term placenta. In CVS sample, ADM expression was found in syncytiotrophoblast and cytotrophoblast. Particularly, the expression of ADM in CVS of preeclampsia patients was reduced.EVCT invasion, migration and integration capability were significantly (P＜0.05) enhanced by ADM (10 nM or 100 nM) treatment for 16-24 hours. In tube formation assay, 100 nM ADM significantly enhanced the tube formation ability of HUVEC cells. In permeability assay, 10 or 100 nM ADM reduced permeability of HUVEC cells. Immunocytochemistry staining of HUVEC cells showed that there was increased expression of cell junction marker, ZO-1 and VE-cadherin, after 10 or 100 nM treatment. In conclusion, Expression of ADM was reduced in term placenta and CVS sample of preeclampsia patients. ADM regulates the functions of human EVCTs and endothelial cells. Further study on the mechanism that regulates the biological activities of ADM would enhance our understanding on the physiology of early pregnancy in humans.