title: G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia.
abstract: BACKGROUND
  Preeclampsia is known to be associated with reduced circulating levels of estrogen. The effects of estrogen in preeclampsia are normally mediated by the classical estrogen receptors. Intriguingly, a novel estrogen receptor, G protein-coupled receptor 30 (GPR30), has been recently found to play an important role in several estrogenic effects. However, the mechanisms by which GPR30 may mediate the development of preeclampsia remain unknown.
  
  
  METHODS
  We observed that the expression of GPR30 in placental trophoblast cells is lower in preeclamptic placentas compared with normotensive controls. We then investigated the role of GPR30 in trophoblast cell invasion by utilizing placental explants and the immortalized human trophoblast cell line (HTR8/SVneo).
  
  
  RESULTS
  The selective GPR30 agonist G1 and a general estrogen receptors agonist 17-β-estradiol (E2) both improved trophoblast cells invasion by upregulating MMP9 expression and the PI3K-Akt signaling pathway. This effect was abolished by a selective GPR30 inhibitor G15, implying that GPR30 may be involved in regulating trophoblast invasion, and that down-regulation of this receptor may result in the development of preeclampsia.
  
  
  CONCLUSIONS
  The present study suggests that GPR30 is a critical regulator of trophoblast cell invasion, and as such may be a potential therapeutic interventional target for preeclampsia and other pregnancy complications resulting from impaired trophoblast invasion.
authors: aDepartment of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University bCanada - China - New Zealand Joint Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, People's Republic of China cLiggins Institute, University of Auckland, Auckland, New Zealand.
authors: Chao
authors: C
authors: Tong
authors: Xiang
authors: X
authors: Feng
authors: Jun
authors: J
authors: Chen
authors: Xingchen
authors: X
authors: Qi
authors: Liyuan
authors: L
authors: Zhou
authors: Shuming
authors: S
authors: Shi
authors: Kamana
authors: K
authors: Kc
authors: Joanna L
authors: JL
authors: Stanley
authors: Philip N
authors: PN
authors: Baker
authors: Hua
authors: H
authors: Zhang
mesh_terms: D002460:Cell Line; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism / Q000502:physiology; D011225:Pre-Eclampsia / Q000378:metabolism / Q000503:physiopathology; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D014327:Trophoblasts / Q000378:metabolism / Q000502:physiology
chemical_list: C109584:GPER1 protein, human; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled