Healthy fish, healthy people: how fish can inform our understanding of effects of metabolism disrupting compound exposure on wildlife and human health
Crawford, Kathryn Anna
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Biologists have traditionally studied adverse health effects of contaminants on wildlife, whereas public health researchers have independently studied effects of the same chemicals on humans. This siloed approach limits maximal progress towards understanding and managing pollution if relevant findings are not translated between fields. A new threat to human health, and potentially ecological health, is metabolic disruption. Metabolism disrupting chemicals (MDCs) are environmental chemicals that can act at systemic and molecular levels across the lifespan to interfere with normal adipose tissue development, lipid storage in the liver, and alter whole-body energetics. Using fish from New Bedford Harbor (NBH), Massachusetts, a marine Superfund site, this research demonstrates the benefit of using a holistic approach to examine exposures to and effects of contaminants in urban waterways. The overall goals of this dissertation were to investigate trends in polychlorinated biphenyl (PCB) contamination in NBH and to test the hypothesis that PCB and/or organotin exposure has resulted in metabolic disruption in Atlantic killifish (Fundulus heteroclitus) resident in New Bedford Harbor. First, trends in PCBs in seafood harvested throughout NBH since 2003 were characterized over time and space. PCBs declined in shellfish, but not finfish, over time. My risk assessment shows that human health risks associated with seafood consumption have decreased, but safe levels in seafood are not likely to be reached by the end of NBH sediment remediation, in the early 2020s. PCBs and tributyltin (TBT), a pollutant also commonly found in commercial harbors because of its use as an antifouling agent in marine paints, act as MDCs by distinct mechanisms. Dioxin-like PCBs act through the aryl hydrocarbon receptor. TBT acts through nuclear receptors, particularly PPARγ and RXR. In the second aim, using historical sediments and current sediments, I document the presence of tin in NBH above background levels. Biological investigations show that adult killifish two generations removed from NBH have more adipose tissue and higher levels of liver triglycerides than killifish from an uncontaminated location. Initial analyses show that changes in PPAR signaling may be particularly important in male killifish. In the third aim, I demonstrate that killifish embryos are minimally responsive to changes in PPARγ-regulated gene expression when treated with TBT or mammalian agonists. However, embryonic TBT exposure interferes with caudal fin development, likely through RXR activation and a reduction in bone formation signaling. Overall, these findings demonstrate metabolic disruption is occurring in a fish species resident to a highly polluted harbor and support the use of sentinel species not only for addressing potential human exposures but also potential adverse human health effects.
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