The role of G protein-associated estrogen receptor (GPER) 1, corin, raftlin, and estrogen in etiopathogenesis of intrauterine growth retardation

Abstract Objective: The aim of the present study was to detect the role of G protein-associated estrogen receptor (GPER) 1, corin, raftlin and estrogen in etiopathogenesis of intrauterine growth retardation (IUGR). Materials and methods: The present study was designed prospectively between January 2017 and May 2018. The study group included 32 patients with unexplained IUGR and 32 healthy pregnant women who gave birth at term among the patients who referred to obstetrics clinic of a tertiary reference hospital. Intrauterine growth retardation (IUGR) was accepted as birth weight below 10th percentile according to the estimated fetal weight. Exclusion criteria were as follows: the patients with renal or hepatic dysfunction, presence of any chronic disease, smoker patients, preeclampsia, acute or chronic inflammatory diseases, body mass index as <18 kg/m2 and >25 kg/m2, structural or chromosomal abnormality in fetus Estradiol (E2), estriol (E3), GPER, corin, and raftlin levels were analyzed in maternal serum and placental tissue homogenate through ELISA method. Results: Serum levels of GPER-1, raftlin, and E3 were significantly lower in IUGR group when compared with the control group (p < .05 for all). Serum corin and E2 levels were similar between two groups. GPER-1, E2, E3, raftlin, and corin levels in placental homogenate were found significantly higher in the control group (p < .05 for all). Conclusion: Although maternal, fetal, and placental causes take place in etiopathogenesis of IUGR, exact etiological factor is not revealed in majority of the IUGR cases. The present study serves as the first study revealing the role of the decrease in GPER-1 and raftlin in maternal serum and placental levels on the etiopathogenesis of IUGR. Furthermore, the decrease in placental corin expression of the cases with IUGR was detected first in the literature. The present study reveals a potential therapeutic use of GPER-1, corin, and raftlin for IUGR.

[1]  E. Kurutaş,et al.  An evaluation of G-protein coupled membrane estrogen receptor-1 level in stuttering , 2018, European Archives of Oto-Rhino-Laryngology.

[2]  Ebru Fındıklı,et al.  Decreased levels of G protein-coupled estrogen receptor in children with autism spectrum disorders , 2017, Psychiatry Research.

[3]  Liyuan Zhou,et al.  Association of a reduction of G-protein coupled receptor 30 expression and the pathogenesis of preeclampsia , 2017, Molecular medicine reports.

[4]  H. Kurahashi,et al.  Increased levels of soluble corin in pre-eclampsia and fetal growth restriction. , 2016, Placenta.

[5]  Ebru Fındıklı,et al.  Serum levels of G protein-coupled estrogen receptor 1 (GPER1) in drug-naive patients with generalized anxiety disorder , 2016, Psychiatry Research.

[6]  Liyuan Zhou,et al.  G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia , 2016, Journal of hypertension.

[7]  D. Sharma,et al.  Intrauterine growth restriction – part 1 , 2016, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[8]  M. Ergin,et al.  Decreased placental and maternal serum TRAIL-R2 levels are associated with placenta accreta. , 2016, Placenta.

[9]  M. Maggiolini,et al.  Pregnancy Augments G Protein Estrogen Receptor (GPER) Induced Vasodilation in Rat Uterine Arteries via the Nitric Oxide - cGMP Signaling Pathway , 2015, PloS one.

[10]  F. F. Abdel Hamid,et al.  Diagnostic utility of BNP, corin and furin as biomarkers for cardiovascular complications in type 2 diabetes mellitus patients , 2015, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[11]  Wonhwa Lee,et al.  Raftlin: a New Biomarker in Human Sepsis , 2014, Inflammation.

[12]  P. Rogers,et al.  Corin, an enzyme with a putative role in spiral artery remodeling, is up-regulated in late secretory endometrium and first trimester decidua. , 2013, Human reproduction.

[13]  W. Cheng,et al.  Role of corin in trophoblast invasion and uterine spiral artery remodelling in pregnancy , 2012, Nature.

[14]  J. Coon,et al.  Estrogen receptor-β and fetoplacental endothelial prostanoid biosynthesis: a link to clinically demonstrated fetal growth restriction. , 2011, The Journal of clinical endocrinology and metabolism.

[15]  P. Yin,et al.  Estrogen receptor-beta mediates cyclooxygenase-2 expression and vascular prostanoid levels in human placental villous endothelial cells. , 2009, American journal of obstetrics and gynecology.

[16]  L. Hui,et al.  Diagnosis and management of fetal growth restriction: the role of fetal therapy. , 2008, Best practice & research. Clinical obstetrics & gynaecology.

[17]  B. Sibai,et al.  Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. , 2006, American journal of obstetrics and gynecology.

[18]  G. V. van Eys,et al.  Uterine Artery Remodeling in Pseudopregnancy Is Comparable to That in Early Pregnancy1 , 2005, Biology of reproduction.

[19]  J. Thorp,et al.  Intrauterine growth restriction increases morbidity and mortality among premature neonates. , 2004, American journal of obstetrics and gynecology.

[20]  A. Yoshimura,et al.  The B cell‐specific major raft protein, Raftlin, is necessary for the integrity of lipid raft and BCR signal transduction , 2003, The EMBO journal.

[21]  T. Regnault,et al.  Placental development in normal and compromised pregnancies-- a review. , 2002, Placenta.

[22]  A. Blann,et al.  Maternal endothelial soluble cell adhesion molecules with isolated small for gestational age fetuses: comparison with pre‐eclampsia , 2001, BJOG : an international journal of obstetrics and gynaecology.

[23]  K. Leveno,et al.  Birth weight in relation to morbidity and mortality among newborn infants. , 1999, The New England journal of medicine.

[24]  J. Ando,et al.  Cloning of cDNAs encoding G protein-coupled receptor expressed in human endothelial cells exposed to fluid shear stress. , 1997, Biochemical and biophysical research communications.