Cargando…

Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans

Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging...

Descripción completa

Detalles Bibliográficos
Autores principales: Shin, Nara, Cuenca, Luciann, Karthikraj, Rajendiran, Kannan, Kurunthachalam, Colaiácovo, Monica P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375566/
https://www.ncbi.nlm.nih.gov/pubmed/30763314
http://dx.doi.org/10.1371/journal.pgen.1007975
_version_ 1783395382301032448
author Shin, Nara
Cuenca, Luciann
Karthikraj, Rajendiran
Kannan, Kurunthachalam
Colaiácovo, Monica P.
author_facet Shin, Nara
Cuenca, Luciann
Karthikraj, Rajendiran
Kannan, Kurunthachalam
Colaiácovo, Monica P.
author_sort Shin, Nara
collection PubMed
description Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. elegans to identify chemicals inducing aneuploidy as a result of impaired germline function. We screened 46 chemicals that are widely present in our environment, but for which effects in the germline remain poorly understood. These included pesticides, phthalates, and chemicals used in hydraulic fracturing and crude oil processing. Of the 46 chemicals tested, 41% exhibited levels of aneuploidy higher than those detected for bisphenol A (BPA), an endocrine disruptor shown to affect meiosis, at concentrations correlating well with mammalian reproductive endpoints. We further examined three candidates eliciting aneuploidy: dibutyl phthalate (DBP), a likely endocrine disruptor and frequently used plasticizer, and the pesticides 2-(thiocyanomethylthio) benzothiazole (TCMTB) and permethrin. Exposure to these chemicals resulted in increased embryonic lethality, elevated DNA double-strand break (DSB) formation, activation of p53/CEP-1-dependent germ cell apoptosis, chromosomal abnormalities in oocytes at diakinesis, impaired chromosome segregation during early embryogenesis, and germline-specific alterations in gene expression. This study indicates that this high-throughput screening system is highly reliable for the identification of environmental chemicals inducing aneuploidy, and provides new insights into the impact of exposure to three widely used chemicals on meiosis and germline function.
format Online
Article
Text
id pubmed-6375566
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-63755662019-03-01 Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans Shin, Nara Cuenca, Luciann Karthikraj, Rajendiran Kannan, Kurunthachalam Colaiácovo, Monica P. PLoS Genet Research Article Chemicals that are highly prevalent in our environment, such as phthalates and pesticides, have been linked to problems associated with reproductive health. However, rapid assessment of their impact on reproductive health and understanding how they cause such deleterious effects, remain challenging due to their fast-growing numbers and the limitations of various current toxicity assessment model systems. Here, we performed a high-throughput screen in C. elegans to identify chemicals inducing aneuploidy as a result of impaired germline function. We screened 46 chemicals that are widely present in our environment, but for which effects in the germline remain poorly understood. These included pesticides, phthalates, and chemicals used in hydraulic fracturing and crude oil processing. Of the 46 chemicals tested, 41% exhibited levels of aneuploidy higher than those detected for bisphenol A (BPA), an endocrine disruptor shown to affect meiosis, at concentrations correlating well with mammalian reproductive endpoints. We further examined three candidates eliciting aneuploidy: dibutyl phthalate (DBP), a likely endocrine disruptor and frequently used plasticizer, and the pesticides 2-(thiocyanomethylthio) benzothiazole (TCMTB) and permethrin. Exposure to these chemicals resulted in increased embryonic lethality, elevated DNA double-strand break (DSB) formation, activation of p53/CEP-1-dependent germ cell apoptosis, chromosomal abnormalities in oocytes at diakinesis, impaired chromosome segregation during early embryogenesis, and germline-specific alterations in gene expression. This study indicates that this high-throughput screening system is highly reliable for the identification of environmental chemicals inducing aneuploidy, and provides new insights into the impact of exposure to three widely used chemicals on meiosis and germline function. Public Library of Science 2019-02-14 /pmc/articles/PMC6375566/ /pubmed/30763314 http://dx.doi.org/10.1371/journal.pgen.1007975 Text en © 2019 Shin et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Shin, Nara
Cuenca, Luciann
Karthikraj, Rajendiran
Kannan, Kurunthachalam
Colaiácovo, Monica P.
Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title_full Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title_fullStr Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title_full_unstemmed Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title_short Assessing effects of germline exposure to environmental toxicants by high-throughput screening in C. elegans
title_sort assessing effects of germline exposure to environmental toxicants by high-throughput screening in c. elegans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375566/
https://www.ncbi.nlm.nih.gov/pubmed/30763314
http://dx.doi.org/10.1371/journal.pgen.1007975
work_keys_str_mv AT shinnara assessingeffectsofgermlineexposuretoenvironmentaltoxicantsbyhighthroughputscreeningincelegans
AT cuencaluciann assessingeffectsofgermlineexposuretoenvironmentaltoxicantsbyhighthroughputscreeningincelegans
AT karthikrajrajendiran assessingeffectsofgermlineexposuretoenvironmentaltoxicantsbyhighthroughputscreeningincelegans
AT kannankurunthachalam assessingeffectsofgermlineexposuretoenvironmentaltoxicantsbyhighthroughputscreeningincelegans
AT colaiacovomonicap assessingeffectsofgermlineexposuretoenvironmentaltoxicantsbyhighthroughputscreeningincelegans