Evaluating mechanisms of environmental chemical exposure with developing zebrafish urinary system

Key Words: Zebrafish, genitourinary development, congenital malformation, translational diagnostics

Many children with improper organ growth before birth have disfigured pelvic organs. In many cases these disfigured organs affect the urinary system: they urinate from more than one hole, their kidneys are blocked, or their bladder is on the outside of their body. Urinary organs must grow properly before birth in order to function and children with improper organ growth face a lifetime of medical procedures, surgery, and doctor’s visits. There is concerning evidence that chemicals in our environment can affect how urinary organs grow. How these chemicals disrupt organ growth is unclear. Zebrafish are frequently used to study such disruptions, but were not thought to have the same urinary organs as humans. Our lab looked closely at zebrafish and discovered they have bladders that hold urine, contract, and even have similar cells to human bladders. This allows us to study how zebrafish bladders grow and change, test what happens to genes when zebrafish are exposed to specific chemicals, and ask questions about the DNA-related changes that may drive problems in growth. Similar studies in “closer” animals like mouse are more difficult. We now use zebrafish to examine bladder growth with advanced DNA-modifying tools and glowing fish to easily see changes in growth. We have already created a computer program capable of seeing differences in normal and abnormal zebrafish bladders. Using the glowing fish, we can see changes more easily and pick only the fish with problems instead of guessing what may be wrong just because the fish was in the wrong water. We would like to accomplish two things. First, we will test whether reported DNA changes after chemical exposure to understand change how organs grow. Second, we will put young zebrafish in water with one of these environmental chemicals, the same way unborn babies and children would be exposed to chemicals when their mothers drink water, and discover new changes in DNA signals than change organ growth. By doing these experiments, we hope to better understand the risks of these thousands of chemicals, learn more about urinary organ growth, and ultimately end these diseases that affect children.