Acute atrazine exposure disrupts matrix metalloproteinases and retinoid signaling during organ morphogenesis in Xenopus laevis

Abstract

Exposure to the herbicide atrazine disrupts many developmental processes in non-target animals. Atrazine exposure during organ morphogenesis in amphibians results in dramatic malformations; the mechanism by which this happens has not been described. We have taken a candidate gene approach to explore two possible mechanisms by which acute atrazine exposure causes extensive malformations in several tissues in Xenopus laevis tadpoles. Using a static renewal system, we exposed tadpoles to atrazine for 6-48 h during organ morphogenesis (Nieuwkoop and Faber stage 42). We observed degradation of cranial cartilage and differentiated muscle in the head, gut and somites of exposed tadpoles. Additionally, transcript levels of matrix metalloproteinases (MMPs), specifically both MMP9TH and MMP18, increased in atrazine-exposed tadpoles in a dose-response test, and MMP18 increased as early as 6 h after exposure began. Gelatinase MMP activity was also altered by atrazine exposure, indicating that atrazine disrupts gene function at the level of transcription and protein activity. Furthermore, transcript levels of the enzyme Xcyp26, an enzyme in the retinoic acid signaling pathway, significantly decreased in the intestines of tadpoles exposed to 10 or 35 mg l(-1) atrazine for 48 h. Our results suggest two mechanisms by which atrazine can disrupt tissue morphogenesis: through misregulation of MMPs that are critical in extracellular matrix remodeling throughout development and the disruption of retinoic acid signaling. This study begins to describe conserved vertebrate developmental processes that are disrupted by atrazine exposure.