G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia

Tong, Chao, Feng, Xiang, Chen, Jun, Qi, Xingchen, Zhou, Liyuan, Shi, Shuming, Kc, Kamana, Stanley, Joanna L., Baker, Philip N. and Zhang, Hua (2016) G protein-coupled receptor 30 regulates trophoblast invasion and its deficiency is associated with preeclampsia. Journal of Hypertension, 34 (4). pp. 710-718. ISSN 0263-6352

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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.  Method: 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.  Conclusion: 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.

Item Type:	Article
Additional Information:	Publisher Copyright: © 2016 Wolters Kluwer Health, Inc.
Uncontrolled Keywords:	g protein-coupled receptor 30 (gpr30),invasion,preeclampsia,trophoblast cells,internal medicine,physiology,cardiology and cardiovascular medicine ,/dk/atira/pure/subjectarea/asjc/2700/2724
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	02 Mar 2026 11:30
Last Modified:	02 Mar 2026 11:30
URI:	https://ueaeprints.uea.ac.uk/id/eprint/102118
DOI:	10.1097/HJH.0000000000000844

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