title: Reproductive toxicity and meiotic dysfunction following exposure to the pesticides Maneb, Diazinon and Fenarimol.
abstract: The comprehensive identification and mechanistic analysis of reproductive toxicants constitutes one of the major hurdles in the toxicological assessment of chemicals originating from the large number of chemicals to be tested and the difficulty in examining germ cells at various stages of their development. We previously described the development of an assay in the roundwormCaenorhabditis elegansthat allows the detection of chemicals bearing aneugenic activity and that could be used for the detection of germline toxicity. We present here new evidence for the reproductive toxicity of three pesticides identified in our germline toxicity assay: Maneb, Diazinon and Fenarimol. We show that all three pesticides cause an acute germline nuclear loss in exposed nematodes in a dose-dependent fashion. The loss of germline nuclei coincides with the meiotic stage of pachytene during Prophase I and is dependent on the germline apoptotic machinery suggesting activation of a meiotic checkpoint. Further investigation revealed a profound dysregulation of the meiotic program revealed by (1) an alteration of the kinetics of double strand repair, (2) the disruption of the process of chromosome morphogenesis at the end of Prophase I and (3) the reorganization of the meiotic differentiation gradient inherent to theC. elegansgermline following exposure to Maneb and Diazinon. These defects correlate with a significant increase in embryonic lethality and a corresponding decrease in the number of progeny. These results therefore provide strong evidence for the reproductive toxicity of Maneb, Diazinon and Fenarimol rooted in the alteration of early steps of germ cell differentiation.
authors.affiliation: Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, USA.
authors.forename: Daniela A
authors.initials: DA
authors.lastname: Parodi
authors.affiliation: Department of Environmental Health Sciences, University of California, Los Angeles, Los Angeles, USA.
authors.forename: Jasmine
authors.initials: J
authors.lastname: Sjarif
authors.affiliation: Department of Environmental Health Sciences, University of California, Los Angeles, Los Angeles, USA ; Molecular Toxicology Inter-Departmental Program, University of California, Los Angeles, Los Angeles, USA.
authors.forename: Yichang
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute for Society and Genetics, University of California, Los Angeles, Los Angeles, USA ; Department of Environmental Health Sciences, University of California, Los Angeles, Los Angeles, USA ; Molecular Toxicology Inter-Departmental Program, University of California, Los Angeles, Los Angeles, USA.
authors.forename: Patrick
authors.initials: P
authors.lastname: Allard
keywords: Caenorhabditis elegans; aneuploidy; chemical screen; reproductive toxicicity