MOLECULAR REGULATION AND DISRUPTION OF THE PROGESTERONE RECEPTOR SIGNALING PATHWAYS DURING FROG EMBRYONIC DEVELOPMENT
Gestagens are a class of steroid hormones capable of binding and activating progesterone receptors. Gestagens include endogenous progestogens, such as progesterone (P4), which have critically important roles in vertebrate physiology and reproduction and synthetic P4 analogues (progestins), such as melengestrol acetate (MGA). Both gestagens are administered as growth promotants in beef cattle and have been measured in surface water receiving runoff from animal agricultural operations. This project aims to understand the roles and the regulatory mechanisms of P4 in early amphibian development and to assess the consequences of exposures to environmental gestagens on the P4-receptor signaling pathways in frog embryos. We first established the developmental transcript profiles of the three P4 receptors in Western clawed frog (Silurana tropicalis) embryos. P4-receptor mRNAs were detected but differentially expressed throughout embryogenesis. Secondly, we conducted P4 and MGA acute exposures to an environmentally realistic range of concentrations to determine the effects of embryonic exposure to gestagens on development, mortality, and gene expression of reproduction-related genes. Acute exposure to P4 induced a 2- to 5-fold change increase of steroid hormone receptor mRNA levels, whereas MGA exposure induced a dissimilar transcriptional profile than P4. Therefore, we conclude that that MGA and P4 may signal through different molecular cascades in frogs. This is the first study to report developmental transcript profiles in embryonic frogs and to assess the molecular effects of MGA exposure in frogs. While our data suggests that P4 and MGA have dissimilar effects, exposure to either P4 or MGA induced multiple endocrine responses and adverse effects at environmentally realistic concentrations in S. tropicalis. Therefore, we conclude that environmental gestagen contamination may pose a risk to wild populations of amphibians.