In pregnancy, trophoblast invasion and uterine spiral artery
remodelling are important for lowering maternal vascular
resistance and increasing uteroplacental blood flow. Impaired
spiral artery remodelling has been implicated in pre-eclampsia,
a major complication of pregnancy, for a long time but the
underlying mechanisms remain unclear. Corin (also known as
atrial natriuretic peptide-converting enzyme) is a cardiac
protease that activates atrial natriuretic peptide (ANP), a
cardiac hormone that is important in regulating blood pressure.
Unexpectedly, corin expression was detected in the pregnant
uterus. Here we identify a new function of corin and ANP in
promoting trophoblast invasion and spiral artery remodelling. We
show that pregnant corin- or ANP-deficient mice developed high
blood pressure and proteinuria, characteristics of
pre-eclampsia. In these mice, trophoblast invasion and uterine
spiral artery remodelling were markedly impaired. Consistent
with this, the ANP potently stimulated human trophoblasts in
invading Matrigels. In patients with pre-eclampsia, uterine
Corin messenger RNA and protein levels were significantly
lower than that in normal pregnancies. Moreover, we have
identified Corin gene mutations in pre-eclamptic
patients, which decreased corin activity in processing pro-ANP.
These results indicate that corin and ANP are essential for
physiological changes at the maternal–fetal interface,
suggesting that defects in corin and ANP function may contribute
to pre-eclampsia.
