Exploring the effects of the herbicide atrazine on tadpoles in the model amphibian Xenopus laevis during organ morphogenesis.

摘要

Environmental chemical contamination is of concern for both wild animal and human populations both because of defined and uncertain risks associated with any given chemical. Human activity contributes directly to this problem in many ways, one of which is the application of pesticides. This dissertation aims to begin to define how the common agricultural herbicide atrazine can affect amphibians, only one of many non-target organisms exposed to the chemical. Use of this herbicide has been highly controversial in recent years due to many factors including its long history of use, persistence in the environment, and contradicting evidence about whether or not chronic exposure causes reproductive anomalies in amphibians. Many studies have examined the effects of atrazine exposure on amphibians early in embryonic development or later in development during metamorphosis. This dissertation fills a gap in previous literature by exploring the effects of acute atrazine exposure during organ morphogenesis, which occurs between embryogenesis and metamorphosis. Using the model amphibian species Xenopus laevis, we first identified organ morphogenesis as being particularly sensitive to atrazine exposure and determined that the observed malformations were specific to atrazine exposure. We have observed dramatic malformations of the intestine, heart, axis, muscle and cartilage following atrazine exposure. We have begun to explore mechanisms to explain why these malformations occur. First, we observed a significant increase in programmed cell death, or apoptosis, in the midbrain and pronephric kidney of atrazine-exposed tadpoles. Additionally, we observed altered gene expression following acute atrazine exposure. Acute atrazine exposure caused an increase in the expression of matrix metalloproteinase enzymes that break down supportive tissue. Specifically, the mRNA expression of MMP18 and MMP9TH as well as gelatinolytic activity are altered in atrazine-exposed tadpoles as compared to non-treated controls. Acute atrazine exposure also disrupts gene expression in the retinoic acid signaling pathway, a pathway for which any perturbation is known to be teratogenic. This dissertation contributes to an ever growing body of research that provides molecular mechanisms by which environmental contaminants can disrupt normal developmental processes.