ENDOCRINE DISRUPTORS IN THE DEVELOPING NERVOUS SYSTEM

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In recent years, both the evidence and the concern have been steadily growing that synthetic compounds, including pesticides, herbicides, and industrial solvents, have deleterious effects on the development of a wide range of species by disrupting endocrine sensitive processes. Numerous studies indicate that these putative endocrine disrupting compounds (EDCs) induce abnormalities in peripheral reproductive organs and in reproductive behaviors (Gray et al, 1992; Cooper and Kavlock, 1997; Reiter et al, 1998). Gonadal steroids are known to have significant and widespread effects on the development of the nervous system (Dohler, 1991), and deficits in neural systems are inferred from studies demonstrating EDC-dependent abnormalities in reproductive behaviors (Gray et al, 1985; Andersen et al, 1997). In spite of these studies, little data is available documenting potential effects of EDCs on cellular processes underlying neuronal differentiation. Moreover, although data clearly suggest that developing organisms are more sensitive to endocrine disruption than adult animals, little information is available delineating critical periods for EDC effects. The goal of the present study is to determine both critical periods and dose-response relationships for putative EDCs in inducing adverse effects on the early embryonic development of vertebrate spinal neurons from the amphibian, Xenopus laevis. Xenopus embryos provide a highly tractable system in which early events underlying formation of the nervous system and establishment of synaptic connections can be screened rapidly in a large number of animals, and in which developmental changes for identified neurons in vivo, as well as these same cells dissociated and maintained in vitro, have been amply documented (Brehm and Henderson, 1988; Spizter, 1994). Using a multidisciplinary approach that includes morphometric analysis, fluorescence microscopy, whole cell patch clamp recording, and ultrafast perfusion techniques, we will determine if exposure to putative estrogenic and anti-androgenic EDCs leads to selective defects in the differentiation of identified populations of spinal cord neurons during early embryonic development.