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Nested case–control study of environmental exposure within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort.

ABSTRACT: Preterm birth is the leading cause of infant mortality worldwide, and also greatly increases the risk of developing serious health complications in childhood and throughout life. Conditions that contribute to preterm birth remain largely unclear, though an influence by environmental exposures is suspected but poorly understood. In our preliminary work, we found that exposure to common chemicals, such as phthalates and bisphenol A (BPA), may contribute to this serious but understudied public health problem. We also observed strong associations between phthalates/BPA and general markers of oxidative stress, and in turn between these general markers of oxidative stress and risk of preterm birth. In this nested case-control study within an ongoing cohort of pregnant women in Puerto Rico (PROTECT), we will explore untargeted lipidomics, as well as levels of eicosanoids specific to arachidonic acid oxidation pathways, in relation to both environmental exposures and preterm birth.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

SUBMITTER: Maureen Kachman

PROVIDER: ST001828 | MetabolomicsWorkbench | Fri Jun 11 00:00:00 BST 2021

REPOSITORIES: MetabolomicsWorkbench

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Project description:Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, precise phenotyping of the preterm birth is hampered 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. The studyâ??s aim was to comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor using precisely phenotyped samples. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified the four groups of patients: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). The largest differences in gene expression among the four groups occurred 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 5â?? and 3â??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. 183 total RNA samples from 8 tissue types collected from 35 women grouped into six categories of pregnancy outcome. One microarray replicate per sample. Other Contributors: Radek Bukowski, Sam Parry and the NICHD Genomic and Proteomic Network for Preterm Birth Research

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Nested case–control study of environmental exposure within the ongoing Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) pregnancy cohort.

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