Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics
| Autor: | David A. MacIntyre, Yun S. Lee, Phillip R. Bennett, Henrik Hagberg, Donald Peebles, Roberta Migale, Mark R. Johnson, Simon N. Waddington, Stefano Cacciatore, Bronwen R. Herbert |
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| Přispěvatelé: | Medical Research Council (MRC) |
| Jazyk: | angličtina |
| Předmět: |
Lipopolysaccharides
0301 basic medicine medicine.medical_specialty Preterm labor Lipopolysaccharide Uterus RNA-Seq Inflammation Andrology Transcriptome Mice 03 medical and health sciences chemistry.chemical_compound Obstetric Labor Premature 0302 clinical medicine Pregnancy General & Internal Medicine Internal medicine Animals Humans Medicine Progesterone Medicine(all) Labor Obstetric 030219 obstetrics & reproductive medicine business.industry Parturition Myometrium 11 Medical And Health Sciences General Medicine medicine.disease 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Models Animal Female Inflammation Mediators medicine.symptom business Research Article Hormone |
| Zdroj: | BMC Medicine Migale, R, MacIntyre, D A, Cacciatore, S, Lee, Y S, Hagberg, H, Herbert, B R, Johnson, M R, Peebles, D, Waddington, S N & Bennett, P R 2016, ' Modeling hormonal and inflammatory contributions to preterm and term labor using uterine temporal transcriptomics ', BMC Medicine, vol. 14, 86, pp. 1-17 . https://doi.org/10.1186/s12916-016-0632-4 |
| ISSN: | 1741-7015 |
| DOI: | 10.1186/s12916-016-0632-4 |
| Popis: | 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 the development of PTL prevention strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12916-016-0632-4) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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