Approaches for assessing the presence and impact of thyroid hormone disrupting chemicals in delphinid cetaceans

Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Massachusetts Institute of Technology and the Woods Hole Oceanographic Institution September 2006Cetacean blubber is a primary site for lipid storage, which the animal utilizes during periods of energetic stress. It is important to understand how the blubber responds to factors such as ontogeny, water temperature, reproductive status, and nutritional state because blubber is also the primary bioaccumulation site for persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs). During periods of lipid mobilization such as lactation, PCBs from the blubber are mobilized into the circulatory system and may cause toxic effects. One particular toxic mechanism may include the induction of cytochrome P450 enzymes in the integument and liver, which could enhance the biotransformation of PCBs to hydroxylated metabolites (OH-PCBs). OH-PCBs may then interfere with thyroid hormone dependent neurodevelopment. The goals of these studies were to investigate the relationships between lipid dynamics and PCB effects and to devise a quantitative approach to assess neurodevelopment in delphinid cetaceans. Blubber morphology, cytochrome P450 1A1 (CYP1A1) expression in the skin-blubber biopsy, blubber and plasma PCBs, and plasma OH-PCBs were assessed in bottlenose dolphins (Tursiops truncatus). In addition, magnetic resonance (MR) images of the postmortem brain in situ were obtained from Atlantic white-sided dolphin (Lagenorhynchus acutus) specimens.These results showed that: 1) Factors such as ontogeny, water temperature, and reproductive status affected blubber morphology in bottlenose dolphins. In response to warmer water, the lipid content of the blubber decreased and this appeared to involve loss of lipids from adipocytes in the middle blubber layer. Similar to the effects of starvation on blubber morphology, lactation decreased adipocyte size predominantly in the deeper blubber, 2) CYP1A1 levels in the deep blubber were significantly related to the total plasma TEQ98 concentrations, adipocyte shrinkage, and plasma OH-PCB levels, 3) Through in situ MR imaging of stranded, Atlantic white-sided dolphin specimens, the size of brain structures that depend on thyroid hormones for maturation could be measured accurately. Future studies can use this technique, coupled with chemical analysis of brain regions, to determine if thyroid hormone disrupting chemicals in delphinid cetaceans are associated with changes in the size of brain structures.Funding for this research was provided by an Environmental Protection Agency STAR fellowship (U-91616101-2) awarded to Eric Montie, NOAA contract #WC1330- 02SE0257, NOAA contract #JHT04P1226, NOAA Fisheries Marine Mammal Health and Stranding Response Program, the Florida Protect Wild Dolphins License Plate Fund, the National Woman’s Farm and Garden Association Scholarship awarded to Eric Montie, Shields MRI and CT of Cape Cod, the Quebec Labrador Fund/Atlantic Center for the Environment, Woods Hole Oceanographic Institution Academic Programs Office, Office of Naval Research, and NOAA Fisheries Marine Mammal Health and Stranding Response Program