Comprehensive assessment of germline chemical toxicity using the nematode Caenorhabditis elegans.
Identifying the reproductive toxicity of the thousands of chemicals present in our environment has been one of the most tantalizing challenges in the field of environmental health. This is due in part to the paucity of model systems that can (1) accurately recapitulate keys features of reproductive processes and (2) do so in a medium- to high-throughput fashion, without the need for a high number of vertebrate animals. We describe here an assay in the nematode C. elegans that allows the rapid identification of germline toxicants by monitoring the induction of aneuploid embryos. By making use of a GFP reporter line, errors in chromosome segregation resulting from germline disruption are easily visualized and quantified by automated fluorescence microscopy. Thus the screening of a particular set of compounds for its toxicity can be performed in a 96- to 384-well plate format in a matter of days. Secondary analysis of positive hits can be performed to determine whether the chromosome abnormalities originated from meiotic disruption or from early embryonic chromosome segregation errors. Altogether, this assay represents a fast first-pass strategy for the rapid assessment of germline dysfunction following chemical exposure.
Institute for Society and Genetics, University of California, Los Angeles.
Daniela A
DA
Parodi
California Nanosystems Institute, Department of Molecular and Medical Pharmacology, University of California, Los Angeles.
Robert
R
Damoiseaux
Institute for Society and Genetics, University of California, Los Angeles; Environmental Health Sciences, University of California, Los Angeles; pallard@ucla.edu.
Patrick
P
Allard
D000782:Aneuploidy; D000818:Animals; D001681:Biological Assay; D017173:Caenorhabditis elegans; D002869:Chromosome Aberrations / Q000139:chemically induced; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D005854:Germ Cells / Q000187:drug effects*; D008297:Male; D012098:Reproduction / Q000187:drug effects; D018675:Toxicity Tests / Q000379:methods*