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

Autor: Zhi Ma, Lin Peng, Sven Mahner, Hellen Ishikawa-Ankerhold, Udo Jeschke, Martina Rahmeh, Anca Chelariu-Raicu, Huixia Yang, Yao Ye, Viktoria von Schönfeldt
Rok vydání: 2021
Předmět:
phosphorylating CREB (pCREB)
Apoptosis
Immune tolerance
Human chorionic gonadotropin
chemistry.chemical_compound
Pregnancy
Cyclic AMP
Biology (General)
Cyclic AMP Response Element-Binding Protein
Progesterone
Spectroscopy
unexplained recurrent miscarriage (uRM)
biology
Chemistry
General Medicine
Middle Aged
Trophoblasts
Computer Science Applications
Cell biology
medicine.anatomical_structure
embryonic structures
Female
lipids (amino acids
peptides
and proteins)
extravillous trophoblast cells (EVTs)
Signal transduction
Signal Transduction
Adult
Abortion
Habitual
QH301-705.5
Prostaglandin E2 receptor
CREB
Article
Catalysis
Cell Line
Inorganic Chemistry
medicine
Humans
Cyclic adenosine monophosphate
ddc:610
Physical and Theoretical Chemistry
Protein kinase A
QD1-999
Molecular Biology
Interleukin-6
Organic Chemistry
Trophoblast
Cyclic AMP-Dependent Protein Kinases
prostaglandin E2 receptor 4 (EP4)
biology.protein
Receptors
Prostaglandin E
EP4 Subtype
Gonadotropins
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 9134, p 9134 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 17
ISSN: 1422-0067
DOI: 10.3390/ijms22179134
Popis: 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.
Databáze: OpenAIRE
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