Neural Progenitors Are Direct Targets of Xenoestrogens in Zebrafish

Abstract

Because a large proportion of endocrine disruptor chemicals (EDC) end up in surface waters, aquatic species are particularly vulnerable to their potential effects. In this regard, fish populations must be carefully monitored for fishes are absolutely crucial in terms of biodiversity and protein resources, but also they are extremely valuable as sentinel species. In this chapter, we discuss EDCs effects on the brain of fish, in particular on radial glial cells, which in all vertebrate species are brain stem cells. Indeed, one of the most prominent effect of EDCs in zebrafish is their impact on the cyp19a1b gene that encodes aromatase B. Strikingly, aromatase B is only expressed in radial glial cells that behave as neuronal progenitors. Detailed molecular and whole animal studies in transgenic zebrafish demonstrated the extreme sensitivity of the cyp19a1b gene to estrogen mimics. In particular, doses as low as 1.5 ng/L of EE2 were consistently shown to turn on cyp19a1b gene expression in 2–5 days old zebrafish embryos. As recent studies indicate that estrogens modulate proliferative activity of radial glia progenitors, it is likely that estrogen mimics may have similar activity. The potential outcome of such effects requires thorough investigations, not only in fish but also in developing mammals. In addition, those studies have led to the development of a very sensitive in vivo assay that makes use of cyp19a1b-GFP transgenic embryos whose brain exhibits GFP expression if exposed to any estrogen mimic acting through estrogen receptors.