Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.
Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.
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作者：
Bukowski R;Sadovsky Y;Goodarzi H;Zhang H;Biggio JR;Varner M;Parry S;Xiao F;Esplin SM;Andrews W;Saade GR;Ilekis JV;Reddy UM;Baldwin DA
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 preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus 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. The largest differences in gene expression among the four groups occurred 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. 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 birth. 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.
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影响因子：
3.7
作者：
Lim S;MacIntyre DA;Lee YS;Khanjani S;Terzidou V;Teoh TG;Bennett PR
通讯作者：
Bennett PR
DOI：
10.1038/nrneph.2014.102
发表时间：
2014-08
期刊：
Nature reviews. Nephrology
影响因子：
--
作者：
Chaiworapongsa T;Chaemsaithong P;Yeo L;Romero R
通讯作者：
Romero R
影响因子：
5.8
作者：
Chan, EC;Fraser, S;Smith, R
通讯作者：
Smith, R
影响因子：
15.8
作者：
Bukowski R;Hankins GD;Saade GR;Anderson GD;Thornton S
通讯作者：
Thornton S
Mirbase：MicroRNA基因组学的工具。
影响因子：
14.9
作者：
Griffiths-Jones, Sam;Saini, Harpreet Kaur;van Dongen, Stijn;Enright, Anton J.
通讯作者：
Enright, Anton J.