Imperial College London
Alternate

DrStefanoCacciatore

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Honorary Research Fellow
 
 
 
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Contact

 

+44 (0)20 7594 2137s.cacciatore

 
 
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Location

 

Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Migale:2016:10.1186/s12916-016-0632-4,
author = {Migale, R and MacIntyre, DA and Cacciatore, S and Lee, YS and Hagberg, H and Herbert, BR and Johnson, MR and Peebles, D and Waddington, SN and Bennett, PR},
doi = {10.1186/s12916-016-0632-4},
journal = {BMC Medicine},
title = {Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics},
url = {http://dx.doi.org/10.1186/s12916-016-0632-4},
volume = {14},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Preterm birth is now recognized as the primary cause of infant mortality worldwide. Interplay between hormonal and inflammatory signaling in the uterus modulates the onset of contractions; however, the relative contribution of each remains unclear. In this study we aimed to characterize temporal transcriptome changes in the uterus preceding term labor and preterm labor (PTL) induced by progesterone withdrawal or inflammation in the mouse and compare these findings with human data. METHODS: Myometrium was collected at multiple time points during gestation and labor from three murine models of parturition: (1) term gestation; (2) PTL induced by RU486; and (3) PTL induced by lipopolysaccharide (LPS). RNA was extracted and cDNA libraries were prepared and sequenced using the Illumina HiSeq 2000 system. Resulting RNA-Seq data were analyzed using multivariate modeling approaches as well as pathway and causal network analyses and compared against human myometrial transcriptome data. RESULTS: We identified a core set of temporal myometrial gene changes associated with term labor and PTL in the mouse induced by either inflammation or progesterone withdrawal. Progesterone withdrawal initiated labor without inflammatory gene activation, yet LPS activation of uterine inflammation was sufficient to override the repressive effects of progesterone and induce a laboring phenotype. Comparison of human and mouse uterine transcriptomic datasets revealed that human labor more closely resembles inflammation-induced PTL in the mouse. CONCLUSIONS: Labor in the mouse can be achieved through inflammatory gene activation yet these changes are not a requisite for labor itself. Human labor more closely resembles LPS-induced PTL in the mouse, supporting an essential role for inflammatory mediators in human "functional progesterone withdrawal." This improved understanding of inflammatory and progesterone influence on the uterine transcriptome has important implications for
AU  - Migale,R
AU  - MacIntyre,DA
AU  - Cacciatore,S
AU  - Lee,YS
AU  - Hagberg,H
AU  - Herbert,BR
AU  - Johnson,MR
AU  - Peebles,D
AU  - Waddington,SN
AU  - Bennett,PR
DO  - 10.1186/s12916-016-0632-4
PY  - 2016///
SN  - 1741-7015
TI  - Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics
T2  - BMC Medicine
UR  - http://dx.doi.org/10.1186/s12916-016-0632-4
UR  - http://hdl.handle.net/10044/1/33899
VL  - 14
ER  -
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