Physiological TLR4 regulation in human fetal membranes as an explicative mechanism of a pathological preterm case.
PPROM
TLR4
cell biology
fetal membrane
genetics
genomics
human
methylome
transcriptome
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
04 02 2022
04 02 2022
Historique:
received:
22
06
2021
accepted:
17
01
2022
entrez:
4
2
2022
pubmed:
5
2
2022
medline:
23
2
2022
Statut:
epublish
Résumé
The integrity of human fetal membranes is crucial for harmonious fetal development throughout pregnancy. Their premature rupture is often the consequence of a physiological phenomenon that has been exacerbated. Beyond all the implied biological processes, inflammation is of primary importance and is qualified as 'sterile' at the end of pregnancy. In this study, complementary methylomic and transcriptomic strategies on amnion and choriodecidua explants obtained from the altered (cervix zone) and intact fetal membranes at term and before labour were used. By cross-analysing genome-wide studies strengthened by in vitro experiments, we deciphered how the expression of toll-like receptor 4 (TLR4), an actor in pathological fetal membrane rupture, is controlled. Indeed, it is differentially regulated in the altered zone and between both layers by a dual mechanism: (1) the methylation of TLR4 and miRNA promoters and (2) targeting by miRNA (let-7a-2 and miR-125b-1) acting on the 3'-UTR of TLR4. Consequently, this study demonstrates that fine regulation of TLR4 is required for sterile inflammation establishment at the end of pregnancy and that it may be dysregulated in the pathological premature rupture of membranes.
Identifiants
pubmed: 35119365
doi: 10.7554/eLife.71521
pii: 71521
pmc: PMC8816379
doi:
pii:
Substances chimiques
3' Untranslated Regions
0
MicroRNAs
0
TLR4 protein, human
0
Toll-Like Receptor 4
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Belville et al.
Déclaration de conflit d'intérêts
CB, FP, MR, CG, BP, DG, VS, LB No competing interests declared
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