Biodistribution and biological impact assessment of micro-plastics water contaminants using a sensitive and reliable Xenopus experimental platform

This research proposal addresses growing concerns about small plastic debris (0.1ƒÝm to 5 mm) or Microplastics (MPs) that have become major pollutants of aquatic ecosystems worldwide and pose serious threats to human health. We propose to leverage a comparative biology approach using the amphibian Xenopus laevis to define the biodistribution of representative environmentally relevant virgin and experimentally aged MPs; and determine how postembryonic exposure to these MPs can induce perturbations of development, fitness, immune homeostasis, chronic inflammation, and poorer antimicrobial immunity that are exacerbated at higher water temperature. Our rationale to leverage X. laevis is that (1) it is a reliable, extensively characterized and widely recognized model of human perinatal and biomedical research; (2) because the post-embryonic development of X. laevis tadpoles is external and not protected by the maternal environment, the immune system differentiation is particularly sensitive to perturbations by water pollutant such as MPs; (3) X. laevis wide thermotolerance is ideal for exploring the influence of temperature on MP biodistribution and biological activity; (4) it is cost effective to expose tadpoles in large numbers to MPs; and (5) X. laevis immune system is remarkably similar to that of humans and we have convincingly established X. laevis as a human health relevant experimental organism to reveal deleterious effects of developmental exposure to water pollutants. To test the hypothesis that developmental exposure to MPs induces perturbations of development, fitness, immune homeostasis, chronic inflammation and poorer antiviral immunity that are exacerbated at higher water temperature, we will determine: (1) the biodistribution of environmentally-relevant virgin and experimentally aged MPs in exposed tadpoles, by visualizing and quantifying the transit, dissemination and accumulation of different types, doses, sizes and treatments of MPs in exposed tadpoles; (2) the effect of water temperature on MP's biodistribution, by comparing the changes in biodistribution and accumulation of various MPs at different temperatures; and (3) the impacts of virgin and aged MPs on development, fitness, immunity, and resistance to pathogens by monitoring the survival, developmental rate, success, and fitness of tadpole exposed to virgin and aged post-consumer MPs for Ontario Lake, as well as by assessing whether later in life young adult frogs have any defects in basal immune function or resistance to infectious diseases. We anticipate that this innovative project will provide crucially needed evidence about biodistribution, biological activity and health risks posed by MPs in water under varied temperatures, including exacerbated or deregulated immune function and resistance to microbial pathogens. In addition, we will identify sensitive and reliable biomarkers useful for human studies. Given the high degree of evolutionary conservation of vertebrate physiology, the expected outcomes from this study will be applicable and relevant to humans.