title: Corin, an enzyme with a putative role in spiral artery remodeling, is up-regulated in late secretory endometrium and first trimester decidua.
abstract: OBJECTIVE
  What is the nature of cellular Corin expression in human gestational tissues?
  
  
  CONCLUSIONS
  CORIN is expressed in non-pregnant late secretory phase endometrium, first trimester human implantation sites and is up-regulated with decidualization ex vivo.
  
  
  BACKGROUND
  Adequate trophoblast invasion and spiral artery remodeling/transformation is critical for successful implantation. CORIN, best known for its role in activating atrial natruietic peptide (ANP) to regulate blood pressure, has recently been proposed to be centrally involved in trophoblast invasion and spiral artery remodeling. It is postulated that ANP, activated by CORIN, promotes trophoblast invasion and that a deficiency causes pre-eclampsia. Mice deficient in either Corin or ANP displayed poor trophoblast invasion, impaired spiral artery remodeling and phenocopied human pre-eclampsia. However, the precise cellular localization of CORIN within human gestational tissues has not been well characterized.
  
  
  METHODS
  We measured CORIN protein localization in a number of human gestational tissues relevant to early embryo/placental implantation: non-pregnant (NP) endometrial biopsies (n = 5 per phase of the menstrual cycle), first trimester placental bed biopsies (n = 12) and pre-term control (n = 10) and severe early onset preeclamptic placentas (n = 15). Endometrial stromal cells were isolated from human endometrial biopsies (n = 5) and induced to decidualize ex vivo. Finally, CORIN concentrations were measured in serum obtained from pregnant women during the first trimester of whom, 56 subsequently ended up with a healthy term delivery (controls), 18 developed fetal growth restriction (FGR) and 21 had a miscarriage.
  
  
  METHODS
  We performed immunohistochemistry to assess CORIN localization. Changes in Corin mRNA expression in human endometrial stromal cells decidualized ex vivo were measured by quantitative RT-PCR, and levels of CORIN within human sera were measured by ELISA.
  
  
  RESULTS
  CORIN was expressed in both NP late secretory phase endometrium and first trimester decidua within placental bed biopsies. Importantly, decidualization of primary human endometrial cells ex vivo significantly increased Corin expression (P < 0.05). CORIN was also detected within the villous cytotrophoblast, but there was no change in mRNA levels in placentas complicated by severe preterm pre-eclampsia when compared with pre-term controls. Although CORIN was detected in first trimester serum, levels did not change across gestation, nor could they predict miscarriage or FGR (other disorders of impaired placental invasion).
  
  
  CONCLUSIONS
  Owing to the fact that we utilized early pregnancy human specimens, this is mainly a descriptive study with a limited amount of functional experiments.
  
  
  CONCLUSIONS
  This is the first study to thoroughly characterize Corin mRNA and protein expression in human gestational tissue. Our findings support recent data from murine studies collectively suggesting that CORIN plays a critical role in trophoblast migration and spiral artery remodeling during early pregnancy in humans. Therefore, further studies of CORIN biology in early pregnancy may identify new therapeutic targets to improve implantation quality in early pregnancy and potentially reduce the rates of pregnancy complications caused by inadequate implantation (pre-eclampsia, FGR and miscarriage).
  
  
  BACKGROUND
  This study was supported by The National Health and Medical Research Council of Australia (Salary support #490970, #490995). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors declare that no competing interests exist.
authors: Translational Obstetrics Group, The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, 163 Studley Rd, Heidelberg, 3084 Victoria, Australia. t.klino@unimelb.edu.au
authors: Tu'uhevaha J
authors: TJ
authors: Kaitu'u-Lino
authors: Louie
authors: L
authors: Ye
authors: Laura
authors: L
authors: Tuohey
authors: Evdokia
authors: E
authors: Dimitriadis
authors: Judith
authors: J
authors: Bulmer
authors: Peter
authors: P
authors: Rogers
authors: Ellen
authors: E
authors: Menkhorst
authors: Michelle
authors: M
authors: Van Sinderen
authors: Jane E
authors: JE
authors: Girling
authors: Natalie
authors: N
authors: Hannan
authors: Stephen
authors: S
authors: Tong
mesh_terms: D000022:Abortion, Spontaneous / Q000235:genetics; D000328:Adult; D001158:Arteries / Q000473:pathology; D001706:Biopsy; D003656:Decidua / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007150:Immunohistochemistry; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011261:Pregnancy Trimester, First; D012697:Serine Endopeptidases / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology; D055815:Young Adult
chemical_list: C119812:CORIN protein, human; D012697:Serine Endopeptidases