Project 3: Discovery of Xenobiotics Associated with Preterm Birth

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SUMMARY The long term goal of this project is to discover xenobiotics that contribute to preterm birth, relying on nontargeted chemical analysis by mass spectrometry. The study is focused on Puerto Rico because the incidence of preterm birth there is the second highest in the world. Three types of samples will be studied: urine, placenta and water. There are five Specific Aims. Specific Aim 1 concerns the urine samples, and studies the hypothesis that preterm urines in Puerto Rico contain a different exposome (xenobiotics or in vivo environmental chemical exposure) than term urines. For this Specific Aim, a large volume (0.5 gallon) of urine as an accumulation of early morning voids is being collected from each pregnant woman, which then is extracted with a porous extraction paddle (stirring "tea bag" filled with 2.0 g of particulate adsorbents). This new technique yields a convenient repository sample (the bag) for shipment, storage, and analysis of aliquots. Specific Aim 2 addresses placenta, since it is the target tissue for postulated environmental chemicals that contribute to preterm birth. Here the hypothesis is that the exposome of women in Puerto Rico (preterm birth rate 17.7%) is different qualitatively or quantitatively than in Boston (preterm birth rate 10.7%). In this Specific Aim, both the organic extractable exposome, and the exposome that has formed DNA adducts, will be tested in placenta. This Specific Aim helps to deal with the possibility that preterm birth is high in Puerto Rico because the exposomes of pregnant women there are high in general without any differences between preterm and term women. Specific Aim 3 focuses on placental cell cultures subjected to oxidative stress and inflammation (that can be caused by xenobiotics), and seeks to learn whether DNA adducts in these stressed cultures are similar to those in preterm placenta from Puerto Rico. Specific Aim 4 seeks to identify pollutants in ground and tap water samples in Puerto Rico, and also corresponding pollutant degradation products when these samples are remediated in Project 5 by electrolysis. Specific Aim 5 proposes to increase the sensitivity, scope, and qualitative capability of current methods for nontargeted chemical analysis by advancing and incorporating derivatization by ionic tagging. The methodology of Specific Aim 5 will be used in the work on Specific Aims 1, 2 and 4. Overall, the project is significant in its potential to help reduce the incidence of preterm birth; in establishing and characterizing by mass spectrometry valuable repository samples from pregnant women from whom extensive demographic information is being collected; and in advancing the usefulness of nontargeted chemical analysis in general for defining the risks from exposure to environmental chemicals.