Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses
| Autor: | Sven Mahner, Nina Ditsch, Markus Sperandio, Myriam Ripphahn, Roland Immler, Martina Rahmeh, Yao Ye, Udo Jeschke, Viktoria von Schönfeldt, Christina Kuhn, Aurelia Vattai |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Endocrinology Diabetes and Metabolism Prostaglandin E2 receptor unexplained recurrent pregnancy losses lcsh:Diseases of the endocrine glands. Clinical endocrinology 03 medical and health sciences 0302 clinical medicine Endocrinology Immune system Internal Medicine medicine Secretion G protein alpha inhibitor 1 ddc:610 Prostaglandin E2 030219 obstetrics & reproductive medicine lcsh:RC648-665 Kinase business.industry Decidua prostaglandin E2 receptor 3 plasminogen activator inhibitor type 1 030104 developmental biology medicine.anatomical_structure Cancer research lipids (amino acids peptides and proteins) business Hormone medicine.drug |
| Zdroj: | Endocrine Connections, Vol 7, Iss 5, Pp 749-761 (2018) |
| Popis: | Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy, and it can stimulate inflammatory reactions via prostaglandin E2 receptor 3 (EP3). However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether EP3 signaling is involved in the mechanism of uRPL. Via immunohistochemistry we could show that the expression of cyclooxygenase-2, EP3 and G protein alpha inhibitor 1 (Gi1) was enhanced in the decidua of the uRPL group in comparison to the control group in first-trimester placentas. In vitro, we demonstrated that sulprostone (an EP1/EP3 agonist) inhibited the secretion of beta-hCG and progesterone in JEG-3 cells and the secretion of beta-hCG in HTR-8/SVneo cells while it induced the expression of plasminogen activator inhibitor type 1 in JEG-3 cells. In addition, PGE2/sulprostone was able to stimulate the expression of Gi1, phosphorylated-extracellular signal-regulated kinases 1/2 (p-ERK1/2) and p53. L-798,106 (an EP3-specific antagonist) suppressed the expression of EP3 and p-ERK1/2 without affecting the secretion of beta-hCG. Elevated activation of EP3 signaling in first-trimester placentas plays an important role in regulating the inflammatory microenvironment, the hormone secretion of extravillous trophoblasts and the remodeling of extracellular matrix in the fetal-maternal interface. L-798,106 might be a ‘potential therapeutic candidate’ for the treatment of uRPL. |
| Databáze: | OpenAIRE |
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