Characterization of an Adapted Murine Model of Intrauterine Inflammation-Induced Preterm Birth.
Journal
The American journal of pathology
ISSN: 1525-2191
Titre abrégé: Am J Pathol
Pays: United States
ID NLM: 0370502
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
10
06
2019
revised:
11
09
2019
accepted:
03
10
2019
pubmed:
15
12
2019
medline:
6
5
2020
entrez:
15
12
2019
Statut:
ppublish
Résumé
Preterm birth (PTB) affects nearly 15 million infants each year. Of these PTBs, >25% are a result of inflammation or infection. Animal models have improved our understanding of the mechanisms leading to PTB. Prior work has described induction of intrauterine inflammation in mice with a single injection of lipopolysaccharide (LPS). Herein, we have improved the reproducibility and potency of LPS in the model using two injections distal to the cervix. An in vivo imaging system revealed more uniform distribution of Evans Blue Dye using a double distal injection (DDI) approach compared with a single proximal injection (SPI). Endotoxin concentrations in vaginal lavage fluid from SPI dams were significantly higher than from DDI dams. At equivalent LPS doses, DDI consistently induced more PTB than SPI, and DDI showed a linear dose-response, whereas SPI did not. Gene expression in myometrial tissue revealed increased levels of inflammatory markers in dams that received LPS DDI compared with LPS SPI. The SPI group showed more significant overexpression in cervical remodeling genes, likely due to the leakage of LPS from the uterine horns through the cervix. The more reliable PTB induction and uniform uterine exposure provided by this new model will be useful for further studying fetal outcomes and potential therapeutics for the prevention of inflammation-induced PTB.
Identifiants
pubmed: 31837289
pii: S0002-9440(19)30850-8
doi: 10.1016/j.ajpath.2019.10.013
pmc: PMC7013271
pii:
doi:
Substances chimiques
Lipopolysaccharides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
295-305Subventions
Organisme : NCI NIH HHS
ID : P30 CA006973
Pays : United States
Organisme : NEI NIH HHS
ID : P30 EY001765
Pays : United States
Organisme : NCRR NIH HHS
ID : S10 RR026824
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001079
Pays : United States
Informations de copyright
Copyright © 2020 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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