Evidence map›Paper›PMID 34502044›Full record

ArticleInternational journal of molecular sciences2021

Prostaglandin E2 Receptor 4 (EP4) Affects Trophoblast Functions via Activating the cAMP-PKA-pCREB Signaling Pathway at the Maternal-Fetal Interface in Unexplained Recurrent Miscarriage.

Lin Peng, Anca Chelariu-Raicu, Yao Ye, Zhi Ma, Huixia Yang, Hellen Ishikawa-Ankerhold, Martina Rahmeh, Sven Mahner, Udo Jeschke, Viktoria von Schönfeldt

Open access · goldAbstract read
In one paragraph

Article in International journal of molecular sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 2 pooled it
0.2field-weighted citation impact, top 49% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 2 syntheses or guidelines pooled it, 9 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Prostaglandin E2 and Progesterone Receptor Coordinately Regulate Primary Cilia for Proper Decidualization.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    Article
  4. Article
  5. Role of CaFrontiers in molecular biosciences · 2025
    Article
  6. Article
  7. Article
  8. Role of protein post-translational modifications in unexplained recurrent pregnancy loss.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Lin PengDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
Anca Chelariu-RaicuDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
Yao YeDepartment of Reproductive Medicine Center, Zhongshan Hospital, Fudan University, Kongjiang Rd. 1665, Shanghai 200092, China.
Zhi MaDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.ORCID 0000-0003-0182-7854
Huixia YangDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.ORCID 0000-0001-8165-621X
Hellen Ishikawa-AnkerholdMedizinische Klinik und Poliklinik I, Klinikum der Universität München, Ludwig-Maximilians-University, 81377 Munich, Germany.ORCID 0000-0003-0307-7022
Martina RahmehDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
Sven MahnerDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.
Udo JeschkeDepartment of Obstetrics and Gynecology, University Hospital, Ludwig-Maximilians-University, Marchioninistr. 15, 81377 Munich, Germany.ORCID 0000-0003-2623-3235
Viktoria von SchönfeldtCenter of Gynecological Endocrinology and Reproductive Medicine, Department of Gynecology and Obstetrics, Ludwig-Maximilians University of Munich, Marchioninistr. 15, 81377 Munich, Germany.
Ludwig-Maximilians-Universität München · DEChongqing Maternal and Child Health Hospital · CNLMU Klinikum · DESun Yat-sen University · CNUniversity Hospital Augsburg · DE

Funding

China Sponsorship Council Zhi Ma, Huixia Yang, Yao Ye
6 · The paper itself

Abstract

Implantation consists of a complex process based on coordinated crosstalk between the endometrium and trophoblast. Furthermore, it is known that the microenvironment of this fetal-maternal interface plays an important role in the development of extravillous trophoblast cells. This is mainly due to the fact that tissues mediate embryonic signaling biologicals, among other molecules, prostaglandins. Prostaglandins influence tissue through several cell processes including differentiation, proliferation, and promotion of maternal immune tolerance. The aim of this study is to investigate the potential pathological mechanism of the prostaglandin E2 receptor 4 (EP4) in modulating extravillous trophoblast cells (EVTs) in unexplained recurrent marriage (uRM). Our results indicated that the expression of EP4 in EVTs was decreased in women experiencing uRM. Furthermore, silencing of EP4 showed an inhibition of the proliferation and induced apoptosis in vitro. In addition, our results demonstrated reductions in β- human chorionic gonadotropin (hCG), progesterone, and interleukin (IL)-6, which is likely a result from the activation of the cyclic adenosine monophosphate (cAMP)- cAMP-dependent protein kinase A (PKA)-phosphorylating CREB (pCREB) pathway. Our data might provide insight into the mechanisms of EP4 linked to trophoblast function. These findings help build a more comprehensive understanding of the effects of EP4 on the trophoblast at the fetal-maternal interface in the first trimester of pregnancy.

Indexed as

Signal TransductionAbortion, HabitualAdultApoptosisCell LineCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinFemaleGonadotropinsHumansInterleukin-6Middle AgedPregnancyProgesteroneReceptors, Prostaglandin E, EP4 SubtypeCREB1 protein, humanCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic AMP Response Element-Binding ProteinGonadotropinsInterleukin-6ProgesteroneReceptors, Prostaglandin E, EP4 Subtypeextravillous trophoblast cells (EVTs)phosphorylating CREB (pCREB)prostaglandin E2 receptor 4 (EP4)unexplained recurrent miscarriage (uRM)

Identifiers

PMID34502044
PMCPMC8430623
OpenAlexW3193449201

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.