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Grantee Research Project Results

Grantee Research Project Results

First-Born Marine Mammals: High Risk for Abnormal Neurodevelopment From Exposure to Environmental Chemicals?

EPA Grant Number: U916161
Title: First-Born Marine Mammals: High Risk for Abnormal Neurodevelopment From Exposure to Environmental Chemicals?
Investigators: Montie, Eric W.
Institution: Massachusetts Institute of Technology
EPA Project Officer: Zambrana, Jose
Project Period: January 1, 2003 through January 1, 2006
Project Amount: $108,172
RFA: STAR Graduate Fellowships (2003)
Research Category: Fellowship - Toxicology , Academic Fellowships , Health Effects

Description:

Objective:

The objective of this research project is to test the hypothesis that first-born marine mammals are at high risk for abnormal neurodevelopment as a result of exposure to persistent organic pollutants (POPs) that interfere with the thyroid hormone (TH) system. THs play an integral part in neurodevelopment. In research studies with rodents, polychlorinated biphenyls (PCBs) and other POPs interfere with TH signaling. These pollutants are widespread in the marine environment and biomagnify in marine mammals to high levels. Thus, PCBs and other environmental contaminants with similar mechanisms of toxicity may affect neuro-development of marine mammals. First-born marine mammals may be particularly sensitive because of increased maternal transfer of POPs during gestation and nursing as compared to subsequent offspring.

Approach:

First, I will determine if specific brain regions in odontocetes and pinnipeds selectively retain higher levels of specific POPs and their metabolites and, if so, determine if the retention can be explained by lipid content or transthyretin (TTR) concentrations. Plasma, blubber, liver, brain regions, and cerebrospinal fluid from deceased animals will be analyzed for POPs, lipid content, and TTR. I also will examine the potential for maternal transfer of certain POPs and metabolites to the fetus and neonate. Fetal/maternal and neonatal/maternal ratios of individual POPs for blubber, plasma, liver, and specific brain regions will be determined. Second, I will determine if odontocetes and pinnipeds are susceptible to the disruption of TH transport by POPs. Using a reverse transcription-polymerase chain reaction approach, mRNA isolated from liver and choroid plexus of select species will be screened for the presence of TTR. From one of these species, the TTR cDNA will be cloned and sequenced, and the TTR protein will be expressed in vitro to examine its affinity for T4, T3, and selected POPs. These characteristics will be directly compared to human TTR expressed in the same manner. Third, I will develop and validate appropriate TH biochemical and molecular markers in marine mammals at the cellular level, and I will determine if these markers are affected in marine mammals contaminated with POPs. Deiodinase (DI, DII, and DIII) activity and expression in the brain, inner ear, pituitary gland, skin/blubber, and liver of pinnipeds and odontocets will be examined. In an epidemiological study, it will be determined if these markers are affected by POPs. Lastly, I will employ clinical imaging techniques—magnetic resonance and x-ray computed tomography—to obtain total brain, hippocampus, cerebellum, and cerebral cortex volumes to test the hypothesis that volume reductions are observed in animals with high levels of POPs.

Supplemental Keywords:

fellowship, marine mammals, neurodevelopment, thyroid hormone, TH, persistent organic pollutant, POP, polychlorinated biphenyl, PCB, transthyretin, TTR.

Relevant Websites:

2004 STAR Graduate Fellowship Conference Poster (PDF, 1p., 224KB, about PDF)

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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