EARLY LIFE STRESS AND PHARMACEUTICAL POLLUTANTS: DEVELOPMENTAL TOXICITY OF EMERGING AQUATIC CONTAMINANTS IN A MODEL TERRESTRIAL SPECIES

Abstract

Trace amounts of pharmaceutical and personal care products are plaguing water sources around the globe, and with no current regulations, these emerging contaminants pose a threat to environmental and human health. While there are dozens of studies describing the toxicity of pharmaceutical pollutants in aquatic organisms, virtually no studies exist pertaining to the potential impacts of environmentally relevant concentrations of these biologically active compounds on terrestrial beings. Further, even less is known about the potential hazards to susceptible populations and the long-lasting effects of chronic exposure. In this dissertation, we investigated the effects of developmental exposure to three abundantly detected pharmaceuticals, fluoxetine, fenofibrate, and norethisterone, in an in ovo chicken model, a well-accepted model of developmental ecotoxicity. Following developmental exposure, general biomarkers of toxicity were evaluated in addition to biomarkers associated specifically with the stress axis. We hypothesized that the developmental stress axis, a highly conserved system among vertebrate species, would serve as a sensitive axis that can be altered by pharmaceutical pollutant exposure. Indeed, in one day old chicken hatchlings, we detected alterations within the stress axis, particularly in DNA methylation alterations. In subsequent studies, we observed persistent molecular changes within the stress axis, including lowered basal corticosterone levels, reduced glucocorticoid receptor content, and insufficient immune responses in developmentally exposed chickens raised to two weeks old. Additionally, we suggest key components of an adverse outcome pathway that could help describe the toxicity of pharmaceutical pollutants in a non-aquatic species. Together, these experiments demonstrate, for the first time, the toxicity of environmental concentrations of pharmaceutical pollutants in a sentinel terrestrial species.