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Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy


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 unclear1,2. 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 pressure3. Unexpectedly, corin expression was detected in the pregnant uterus4. 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.

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Figure 1: Hypertension, proteinuria and renal pathology in pregnant Corin knockout and knockout/transgenic mice.
Figure 2: Impaired trophoblast invasion and spiral artery remodelling in Corin knockout and knockout/transgenic mice.
Figure 3: Hypertension, proteinuria and uteroplacental pathology in pregnant ANP knockout mice.
Figure 4: ANP-stimulated human trophoblast invasion, and impaired uterine Corin expression and Corin mutations in pre-eclamptic patients.


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We thank J. Robbins for the α-myosin heavy chain promoter construct and L. Zhang for help with statistical analysis. This work was partly supported by grants from the Ralph Wilson Medical Foundation, the Bakken Heart-Brain Institute and the National Institutes of Health (HL089298, HD064634), and by grants from the National Natural Science Foundation of China (31070716, 81170247 and 31161130356) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

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Y.C., W.W., N.D., J.L., D.K.S., M.L., C.F., J.P., S.C., S.W., Z.L. and L.D. designed and performed experiments. N.D., W.C. and X.H. collected patient samples and analysed clinical data. Q.W. conceived the study and designed experiments. Y.Z. and Q.W. wrote the manuscript. All authors analysed and interpreted data, and critically read the manuscript.

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Correspondence to Qingyu Wu.

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The authors declare no competing financial interests.

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Cui, Y., Wang, W., Dong, N. et al. Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy. Nature 484, 246–250 (2012).

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