(Project 2 - Pearson, Swanson) Polychlorinated biphenyls (PCBs), one of a number of chlorinated organic pollutants, are highly lipid-soluble toxins that are characterized by relative chemical stability and prevalence in the environment. These traits are responsible for their widely recognized role as a source of serious environmental public health risks. PCBs have been shown to cross the placenta and enter breast milk, and a recent paper suggests that prenatal organochlorine levels contribute to gender-specific obesity development in children. In a mouse model, additional observations revealed that offspring exposed perinatally to PCB 126, a coplanar PCB that acts through the aryl hydrocarbon receptor, had significantly worse fat and lean mass profiles compared to offspring born to vehicle-treated dams. Further, mature offspring born to PCB-exposed dams had impaired glucose tolerance compared to offspring from vehicle-treated dams. The principal investigator's group has shown that short-term maternal voluntary exercise prior to and during healthy pregnancy and nursing can enhance long- term glucose homeostasis in offspring. The goal of the proposed research is to elucidate the potential long- term health complications and mechanisms of PCB toxicity during the critical periods of in utero and early postnatal life and to explore maternal exercise as a transgenerational intervention.
Specific Aim 1 will establish the importance of the timing of perinatal PCB exposure (unexposed/in utero exposure/postnatal exposure/in utero + postnatal exposure) that precipitates impaired glucose tolerance in offspring. A subset of offspring will be fed a high fat diet to determine whether a 'second hit'will exacerbate the PCB-induced detriments.
Specific Aim 2 will elucidate the mechanism of impaired glucose tolerance in offspring born to PCB-exposed dams.
Specific Aim 3 will test if voluntary maternal exercise can be used as an intervention to protect adult offspring from the long-term effects of perinatal PCB exposure. The proposed studies will provide new etiological evidence supporting current observations that perinatal exposures to environmental PCBs are important contributors to the epidemic of diabetes in the United States. This work will also contribute innovative new insights to understanding the role of exercise in mitigating the environmental health impacts of PCB exposure by highlighting pregnancy as a sensitive period when environmental pollutants could have significant and long- lasting effects on offspring metabolism and when interventions could prove effective in ameliorating the detrimental health outcomes. Anticipated results are particularly significant in that they highlight early developmental stages, i.e., fetal and neonatal, as potential periods of particular vulnerability to lasting effects of toxic environmental insult from PCB contamination.

Public Health Relevance

Obesity and diabetes are at epidemic levels, and the toxicity of environmental contaminants during perinatal development could be a significant contributor to these trends. The proposed studies will provide novel information on the detrimental impact that pollutants can have on maternal and offspring health and will test whether the lifestyle intervention, maternal exercise, can attenuate these effects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES007380-17A1
Application #
8649939
Study Section
Special Emphasis Panel (ZES1-LKB-K (S))
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
17
Fiscal Year
2014
Total Cost
$330,976
Indirect Cost
$87,976
Name
University of Kentucky
Department
Type
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Murphy, Margaret O; Petriello, Michael C; Han, Sung Gu et al. (2016) Exercise protects against PCB-induced inflammation and associated cardiovascular risk factors. Environ Sci Pollut Res Int 23:2201-11
Perkins, Jordan T; Petriello, Michael C; Newsome, Bradley J et al. (2016) Polychlorinated biphenyls and links to cardiovascular disease. Environ Sci Pollut Res Int 23:2160-72
Platt, Kristen M; Charnigo, Richard J; Shertzer, Howard G et al. (2016) Branched-Chain Amino Acid Supplementation in Combination with Voluntary Running Improves Body Composition in Female C57BL/6 Mice. J Diet Suppl 13:473-86
Wahlang, Banrida; Petriello, Michael C; Perkins, Jordan T et al. (2016) Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases. Toxicol In Vitro 35:180-7
Pennell, Kelly G; Scammell, Madeleine K; McClean, Michael D et al. (2016) Field data and numerical modeling: A multiple lines of evidence approach for assessing vapor intrusion exposure risks. Sci Total Environ 556:291-301
Hunt, Gary; Stegeman, John; Robertson, Larry (2016) PCBs: exposures, effects, remediation, and regulation with special emphasis on PCBs in schools. Environ Sci Pollut Res Int 23:1971-4
Liu, Dandan; Perkins, Jordan T; Hennig, Bernhard (2016) EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells. J Nutr Biochem 28:164-70
Kania-Korwel, Izabela; Lehmler, Hans-Joachim (2016) Chiral polychlorinated biphenyls: absorption, metabolism and excretion-a review. Environ Sci Pollut Res Int 23:2042-57
Petriello, Michael C; Hoffman, Jessie B; Sunkara, Manjula et al. (2016) Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors. J Nutr Biochem 33:145-53
Baker, Nicki A; Shoemaker, Robin; English, Victoria et al. (2015) Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice. Environ Health Perspect 123:944-50

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