Corin, a protein involved in spiral arteriole remodelling in mice, is expressed in human endometrium and the villous cytotrophoblast — ASN Events

Corin, a protein involved in spiral arteriole remodelling in mice, is expressed in human endometrium and the villous cytotrophoblast (#285)

Laura T Tuohey 1 , Tu’uhevaha J Kaitu’u-Lino 1 , Louie Ye 1 , Ellen Menkhorst 2 , Eva Dimitriadis 2 , Stephen Tong 1
  1. Mercy Hospital for Women, University of Melbourne, Heidelberg, Victoria, Australia
  2. Prince Henry's Institute, Clayton, Victoria, Australia

Corin has recently been proposed as a new protein involved in trophoblast invasion and hypothesised to be a major contributor to the early pathogenesis of preeclampsia1. Prior to this report, Corin was best characterised for its role in activating a hormone important for regulation of blood pressure, atrial natriuretic peptide (ANP). Interestingly, pregnant mice deficient in corin or ANP developed characteristics of pre-eclampsia including high blood pressure and proteinuria and were shown to have deficient trophoblast invasion and uterine spiral artery remodelling.

However, Corin expression in human gestational tissue remains very ill defined. In the original report by Cui et al1, they described decreased mRNA and protein levels of Corin in ‘uterine biopsies’ from preeclamptic cases without defining tissue localisation.

The objective of this study was to further define Corin expression in human tissues. We examined whether Corin is expressed in uterine tissue, preeclamptic placenta and assessed changes in corin serum levels across early pregnancy.

Corin immunohistochemistry on endometrial tissue from across the menstrual cycle indicated patchy glandular epithelial staining in the early-late secretory phase with no stromal staining. Surprisingly, there was no obvious decidual staining. In a cohort of severe preeclamptic (n=20) and gestationally matched pre-term placentas (n=10), we confirmed the expression of Corin by PCR mRNA. Immunohistochemistry showed strong staining in the villous cytotrophoblast, the same site as has been previously reported for ANP2. There was little staining in the syncytiotrophoblast. While undetectable in conditioned media from endometrial decidua, placental explants or trophoblast cell lines, Corin was readily detectable in early pregnancy sera. However, there no change across gestation between 7-11 weeks (n=10-15 per gestation), the period of spiral arteriole remodelling.

In conclusion, Corin exhibits only patchy expression in the glandular endometrial epithelium, no decidual staining and is strongly expressed in cytotrophoblast cells. It is secreted into the maternal circulation, but levels in serum do not vary in early pregnancy. Thus, although Cui et al1 provided strong evidence for a role for Corin in mouse pregnancy, its definitive role in human pregnancy is still unclear.

  1. 1 Cui et al. Nature (2012) 484: 246-252
  2. 2 Graham et al, BOR (1996), 54:834-840