Early pregnancy peripheral blood gene expression and risk of preterm delivery: a nested case control study

Abstract

BackgroundPreterm delivery (PTD) is a significant public health problem associated with greater risk of mortality and morbidity in infants and mothers. Pathophysiologic processes that may lead to PTD start early in pregnancy. We investigated early pregnancy peripheral blood global gene expression and PTD risk.MethodsAs part of a prospective study, ribonucleic acid was extracted from blood samples (collected at 16 weeks gestational age) from 14 women who had PTD (cases) and 16 women who delivered at term (controls). Gene expressions were measured using the GeneChip® Human Genome U133 Plus 2.0 Array. Student's T-test and fold change analysis were used to identify differentially expressed genes. We used hierarchical clustering and principle components analysis to characterize signature gene expression patterns among cases and controls. Pathway and promoter sequence analyses were used to investigate functions and functional relationships as well as regulatory regions of differentially expressed genes.ResultsA total of 209 genes, including potential candidate genes (e.g. PTGDS, prostaglandin D2 synthase 21 kDa), were differentially expressed. A set of these genes achieved accurate pre-diagnostic separation of cases and controls. These genes participate in functions related to immune system and inflammation, organ development, metabolism (lipid, carbohydrate and amino acid) and cell signaling. Binding sites of putative transcription factors such as EGR1 (early growth response 1), TFAP2A (transcription factor AP2A), Sp1 (specificity protein 1) and Sp3 (specificity protein 3) were over represented in promoter regions of differentially expressed genes. Real-time PCR confirmed microarray expression measurements of selected genes.ConclusionsPTD is associated with maternal early pregnancy peripheral blood gene expression changes. Maternal early pregnancy peripheral blood gene expression patterns may be useful for better understanding of PTD pathophysiology and PTD risk prediction.

Development and validation of a spontaneous preterm delivery predictor in asymptomatic women

“…Current "omics" studies suggest that perturbations in the physiological state of pregnancy can be detected in maternal serum analytes measured in sPTD subjects. "Omics" discovery studies in PTD have included proteomic, 10,12,13,[31][32][33][34] transcriptomic, [35][36][37] genomic, [38][39][40][41][42] and metabolomic 43 approaches. However, to date, none of these approaches has produced validated testing methods to reliably predict the risk of sPTD in asymptomatic women.…”

A Bioinformatics Approach to Preterm Birth

“…We included the genes and genetic variants identified by curation and in public databases, largely transcriptome wide array data sets 5,6 and some proteomic analyses related to preterm birth. 7 The genes identified by the ingenuity pathway analysis were entered into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.…”

“…We used the ingenuity pathway analysis (IPA, Ingenuity ® Systems, www.ingenuity.com) to identify pathways and networks involving the genes we identified with significant evidence for their roles in preterm birth. We included the genes and genetic variants identified by curation and in public databases, largely transcriptome wide array data sets 5,6 and some proteomic analyses related to preterm birth. 7 The genes identified by the ingenuity pathway analysis were entered into the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.…”

Transcriptome analysis of early pregnancy vitamin D status and spontaneous preterm birth

“…Gene expression profiling can be useful for identifying pathway genes that provide insight into understanding the molecular mechanisms responsible for sPTB at early pregnancy. Previous research has looked at early pregnancy peripheral blood gene expression in patients who had preterm deliveries, each finding a set of genes that can be explored further for their roles in PTB [19,20]. Therefore, gene expression profiling could be employed as a helpful tool for exploring the biological pathways related to early pregnancy vitamin D status that may contribute to sPTB.…”