Abstract Sub-lethal toxic effects of Bisphenol A on Caenorhabditis elegans: the role of stress resistance genes in BPA-induced growth inhibition by Zailene Flood

Sub-lethal toxic effects of Bisphenol A on Caenorhabditis elegans: the role of stress resistance genes in BPA-induced growth inhibition by Zailene Flood July, 2014 Director: Xiaoping Pan DEPARTMENT OF BIOLOGY Endocrine disrupting chemicals (EDCs) have become of concern for a variety of health issues. Bisphenol-A (BPA) is a widely studied EDC and has been characterized by its estrogen-like effects. BPA is a prevalent component in polycarbonate plastics, having one of the highest production volumes in the world. Humans are exposed to BPA in products such as water bottles, dental sealants and on the inside of food and beverage cans. Due to frequent human exposure to BPA, research on the resulting biological effects is highly significant. In this study, we utilized the model organism Caenorhabditis elegans (C. elegans) to investigate potential impacts of BPA on growth, reproduction, locomotion and feeding behaviors and gene expressions. At dosage of 1.0 μM of BPA exposure from L1 stage to adulthood, the worm’s body size was significantly reduced. To test the hypothesis that BPA exposure may associated with obesity risk, we conducted Oil Red O staining to test fat storage in worms exposed to 0.1 and 1.0 μM of BPA exposure from L1 stage to adulthood, using glucose as a positive control. However, our results show that the body fat storage decreased when exposed to BPA at both tested concentrations. For behavior assays, worms experienced a decrease in locomotion speed when exposed to high concentration of BPA (1.0 μM) and a stimulation of locomotion speed at low concentration BPA exposure (0.1 μM). Attainment levels of worms were significantly decreased in the high concentration treatment group. At the first 8 hrs of observation, less than 10% of 1.0 μM of BPA treated worms were able to reach the food source. Additionally, high BPA exposure (1.0 μM) decreased egg productions throughout the egg-laying period. The brood size of 1.0 μM treated worms was reduced to 7% of control. In contrast, low BPA treatment group (0.1 μM) significantly increased early egg laying between 65-96 hr period after L1. The expression of 3 (egl-10, sod-1 and old-1) selected genes were affected significantly. Changes in gene expression were more evident at high dosage than at the relatively low level. Egl-10 and old-1 genes implicated in egg-laying and stress resistance was upregulated by BPA. Sod-1 associated with protecting cells from oxidative damaged was down regulated. Other tested genes were cat-4, egl-5, egl-19, egl-44, egl-46, egl-47, pink-1, age-1, old-1 and ric-3. Together these results suggest BPA-associated reproductive toxicity and neurobehavioral deficits. Sub-lethal toxic effects of Bisphenol-A on Caenorhabditis elegans: the role of stress resistance genes in BPA-induced growth inhibition A Thesis Presented To The Faculty of the Department of Biology East Carolina University In Partial Fulfillment of the Requirements for the Degree Master of Science by Zailene Flood July, 2014 ©Copyright 2014 Zailene Flood Sub-lethal toxic effects of Bisphenol-A on Caenorhabditis elegans: the role of stress resistance genes in BPA-induced growth inhibition