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Prostaglandin E₂ receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses.

ABSTRACT: 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 (G_i1) 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 G_i1, 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.

SUBMITTER: Ye Y

PROVIDER: S-EPMC5958745 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses.

Ye Yao Y Vattai Aurelia A Ditsch Nina N Kuhn Christina C Rahmeh Martina M Mahner Sven S Ripphahn Myriam M Immler Roland R Sperandio Markus M Jeschke Udo U von Schönfeldt Viktoria V

Endocrine connections 20180426 5

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 invest ...[more]

PMID: 29700097

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Project description:ObjectiveTo study decidualization-associated endometrial factors.DesignRetrospective cohort study to compare endometrial gene expression patterns in women experiencing reproductive failure including recurrent pregnancy loss or unexplained infertility versus fertile controls.SettingUniversity Reproductive Medicine Center.PatientsWomen experiencing recurrent reproductive failure including recurrent pregnancy loss or unexplained infertility (n = 42) and fertile controls (n = 18).InterventionsEndometrial biopsy samples were analyzed with targeted ribonucleic acid sequencing via next-generation sequencing.Main outcome measuresThe primary end point measurements were the expression of genes important for endometrial transformation during decidualization measured singly and in a combined/cumulative score approach. The secondary end point measurements were receiver operating curve analysis and comparisons between the specific biomarkers.ResultsThe comparison revealed differential expression of factors associated with decidualization, tissue homeostasis, and immune regulation: FOXO1, GZMB, IL15, SCNN1A, SGK1, and SLC2A1. A combined evaluation of these 6 signature factors was designated as a decidualization score in which the maximal score was "6" and the minimal was "0". Among controls, 89% of the samples had a score ≥5 and 11% had a score of "4". A total of 76% of samples in the patient group had scores ≤4 and 19% had the lowest score of "0". A decidualization score <4 provided evidence of abnormality in the decidualization process with a sensitivity of 76% (95% CI 61%-88%) and specificity of 89% (95% CI 65%-99%).ConclusionsDecidualization scoring can determine whether the endometrial molecular profile is implantation-friendly. Further validation of this testing approach is necessary to determine a particular patient population in whom it could be used for selecting patients that require therapeutic actions to improve endometrial conditions prior to the in vitro fertilization procedure.

Dataset Information

Prostaglandin E₂ receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses.

Publications

Prostaglandin E<sub>2</sub> receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses.

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