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Thesis: Ling LI

When Jul 09, 2014
from 01:30 to 05:30
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Development problems induced by endocrine disruptors (EDCs) are currently understudied. However, early exposure to EDCs may lead to deleterious and permanent problems in later lifetime. Zebrafish (Danio rerio) transgenic lines with tissue-specific expression of GFP are useful tools to identify the organs affected by a given compound. We have used 7 transgenic lines to visualize in vivo whether 6 known EDCs and 3 other pharmaceuticals can alter organogenesis during development of zebrafish. This screen revealed that 4 chemicals have effects on 4 different organs. The EDC tetrabromobisphenol-A, as well as the tested medicines (diclofenac, trichostatin A and valproic acid) disrupt vascular system development in zebrafish embryo. Moreover, HDAC inhibitors trichostatin A and valproic acid inhibit both endocrine and exocrine pancreas development. Developmental delays were also induced by trichostatin A and valproic acid in the liver and in the pharyngeal teeth.

Traditional Chinese medicines (TCMs) are important components of modern medicine. However we know little about the biological activities of TCMs compounds during development. We used zebrafish embryos to study the effects of 3 plants and 5 of their major compounds on the development. We observed that zebrafish embryogenesis was delayed by water extracts from Astragalus membranaceus and Akebia quinata. We also found that the vascular development was affected at different levels by Salvia miltiorrhiza water extracts and by its 3 major components either used alone or mixed together. Our results show that EDCs and TCMs can cause problems during zebrafish embryogenesis. They also show that zebrafish is a powerful tool for rapid in vivo screening of small molecules and their effects on development. This work also enables us to draw a parallel between EDC and some TCMS, which may act on similar targets, such as nuclear receptors.

Key words:

Endocrine disrupting chemicals (EDCs), Traditional Chinese Medicine (TCMs), exposure, Zebrafish, embryo, screening, transgenic lines, development, Nuclear receptor (NR)