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.

Public Health Relevance

Exposure of pregnant women to environmental chemicals may be contributing to the high rate of preterm birth worldwide. In this project we are seeking evidence for the role of chemical exposure in preterm birth by exploring the chemical composition of urine and placental samples from pregnant women, and also of water that they drink and use for bathing and cooking. Our work could lead to more understanding of preterm birth, and new regulations for chemical exposures that decrease its incidence.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES017198-05
Application #
8649397
Study Section
Special Emphasis Panel (ZES1-LKB-K (S))
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
5
Fiscal Year
2014
Total Cost
$248,497
Indirect Cost
$88,692
Name
Northeastern University
Department
Type
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115
Watkins, Deborah J; Ferguson, Kelly K; Anzalota Del Toro, Liza V et al. (2015) Associations between urinary phenol and paraben concentrations and markers of oxidative stress and inflammation among pregnant women in Puerto Rico. Int J Hyg Environ Health 218:212-9
Yu, Xue; Ghasemizadeh, Reza; Padilla, Ingrid et al. (2015) Spatiotemporal changes of CVOC concentrations in karst aquifers: analysis of three decades of data from Puerto Rico. Sci Total Environ 511:10-Jan
Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu et al. (2015) Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth. Am J Obstet Gynecol 212:208.e1-8
Boldenow, Erica; Hogan, Kelly A; Chames, Mark C et al. (2015) Role of cytokine signaling in group B Streptococcus-stimulated expression of human beta defensin-2 in human extraplacental membranes. Am J Reprod Immunol 73:263-72
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Ferguson, Kelly K; Cantonwine, David E; Rivera-González, Luis O et al. (2014) Urinary phthalate metabolite associations with biomarkers of inflammation and oxidative stress across pregnancy in Puerto Rico. Environ Sci Technol 48:7018-25
Ferguson, Kelly K; McElrath, Thomas F; Ko, Yi-An et al. (2014) Variability in urinary phthalate metabolite levels across pregnancy and sensitive windows of exposure for the risk of preterm birth. Environ Int 70:118-24
Korir, Michelle L; Knupp, David; LeMerise, Kathryn et al. (2014) Association and virulence gene expression vary among serotype III group B streptococcus isolates following exposure to decidual and lung epithelial cells. Infect Immun 82:4587-95
Yao, Yuanyuan; Wang, Poguang; Giese, Roger (2014) Evaporative derivatization of phenols with 2-sulfobenzoic anhydride for detection by matrix-assisted laser desorption/ionization mass spectrometry. Rapid Commun Mass Spectrom 28:653-61
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