Journal article
Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface
PeerJ (San Francisco, CA), Vol.5(9), p.e3685
09/01/2017
DOI: 10.7717/peerj.3685
PMCID: PMC5582610
PMID: 28879060
Abstract
Background. Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterrn and term partuntion.
Methods. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fungus and lower segment (n=183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes.
Results. The largest differences in gene expression among the four groups occur red at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5' and 3' UTR regions.
Conclusions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding. by, the activation of multiple pathways of the immune system in the Preterm Complications of the pregnancy associated with impairment of placental function, which necessitated. premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.
Details
- Title: Subtitle
- Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface
- Creators
- Radek Bukowski - The University of Texas at AustinYoel Sadovsky - Magee-Womens Research InstituteHani Goodarzi - University of California, San FranciscoHeping Zhang - Yale UniversityJoseph R. Biggio - University of Alabama at BirminghamMichael Varner - University of UtahSamuel Parry - University of PennsylvaniaFeifei Xiao - University of South CarolinaSean M. Esplin - Intermountain HealthcareWilliam Andrews - University of Alabama at BirminghamGeorge R. Saade - The University of Texas Medical Branch at GalvestonJohn V. Ilekis - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUma M Reddy - Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentDonald A. Baldwin - Signal GeneticsEunice Kennedy Shriver National Institute of Child Health and Human Development Genomic and Proteomic Network for Preterm Birth ResearchJeffrey C Murray (Contributor)
- Resource Type
- Journal article
- Publication Details
- PeerJ (San Francisco, CA), Vol.5(9), p.e3685
- DOI
- 10.7717/peerj.3685
- PMID
- 28879060
- PMCID
- PMC5582610
- NLM abbreviation
- PeerJ
- ISSN
- 2167-8359
- eISSN
- 2167-8359
- Publisher
- Peerj Inc
- Number of pages
- 29
- Grant note
- U01-HD-050062; U01-HD-050078; U01-HD-050080; U01-HD-050088; U01-HD-050094 / Eunice Kennedy Shriver National Institute of Child Health and Human Development Genomic and Proteomic Network for Preterm Birth Research
- Language
- English
- Date published
- 09/01/2017
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9985034988702771
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