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Rapid identification of reproductive toxicants among environmental chemicals using an in vivo evaluation of gametogenesis in budding yeast Saccharomyces cerevisiae

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Název: Rapid identification of reproductive toxicants among environmental chemicals using an in vivo evaluation of gametogenesis in budding yeast Saccharomyces cerevisiae
Autoři: Kumar, Ravinder, Oke, Ashwini, Rockmill, Beth, de Cruz, Matthew, Verduzco, Rafael, Shodhan, Anura, Woodruff-Madeira, Xavier, Abrahamsson, Dimitri P, Varshavsky, Julia, Lam, Juleen, Robinson, Joshua F, Allard, Patrick, Woodruff, Tracey J, Fung, Jennifer C
Zdroj: Reproductive Toxicology, vol 128
Informace o vydavateli: Elsevier BV, 2024.
Rok vydání: 2024
Témata: reproductive toxicity, High-Throughput Screening Assays (mesh), 1117 Public Health and Health Services (for), Endocrine Disruptors, Toxicology, Gametogenesis, Toxicity Tests (mesh), Contraception/Reproduction (rcdc), 3215 Reproductive medicine (for-2020), Animals (mesh), meiosis, Environmental Pollutants (mesh), 32 Biomedical and Clinical Sciences (for-2020), high-throughput, 3214 Pharmacology and Pharmaceutical Sciences (for-2020), 3 Good Health and Well Being (sdg), Estradiol, Reproduction, Pharmacology and Pharmaceutical Sciences, Public Health and Health Services, Environmental Pollutants, infertility, Endocrine Disruptors (rcdc), Estradiol (mesh), 3215 Reproductive Medicine (for-2020), Benzhydryl Compounds (mesh), Saccharomyces cerevisiae, 1114 Paediatrics and Reproductive Medicine (for), gametogenesis, Paediatrics and Reproductive Medicine, Phenols, Gametogenesis (mesh), Toxicity Tests, Reproduction (mesh), Animals, Toxicology (science-metrix), Saccharomyces cerevisiae (mesh), quaternary ammonium compounds, Benzhydryl Compounds, Endocrine Disruptors (mesh), Biomedical and Clinical Sciences, 1115 Pharmacology and Pharmaceutical Sciences (for), Contraception/Reproduction, Phenols (mesh), High-Throughput Screening Assays, Good Health and Well Being, Reproductive Medicine, bisphenols, Infertility, NAM, 3214 Pharmacology and pharmaceutical sciences (for-2020), Infertility (rcdc)
Popis: Infertility affects ∼12 % of couples, with environmental chemical exposure as a potential contributor. Of the chemicals that are actively manufactured, very few are assessed for reproductive health effects. Rodents are commonly used to evaluate reproductive effects, which is both costly and time consuming. Thus, there is a pressing need for rapid methods to test a broader range of chemicals. Here, we developed a strategy to evaluate large numbers of chemicals for reproductive toxicity via a yeast, S. cerevisiae high-throughput assay to assess gametogenesis as a potential new approach method (NAM). By simultaneously assessing chemicals for growth effects, we can distinguish if a chemical affects gametogenesis only, proliferative growth only or both. We identified a well-known mammalian reproductive toxicant, bisphenol A (BPA) and ranked 19 BPA analogs for reproductive harm. By testing mixtures of BPA and its analogs, we found that BPE and 17 β-estradiol each together with BPA showed synergistic effects that worsened reproductive outcome. We examined an additional 179 environmental chemicals including phthalates, pesticides, quaternary ammonium compounds and per- and polyfluoroalkyl substances and found 57 with reproductive effects. Many of the chemicals were found to be strong reproductive toxicants that have yet to be tested in mammals. Chemicals having affect before meiosis I division vs. meiosis II division were identified for 16 gametogenesis-specific chemicals. Finally, we demonstrate that in general yeast reproductive toxicity correlates well with published reproductive toxicity in mammals illustrating the promise of this NAM to quickly assess chemicals to prioritize the evaluation for human reproductive harm.
Druh dokumentu: Article
Popis souboru: application/pdf
Jazyk: English
ISSN: 0890-6238
DOI: 10.1016/j.reprotox.2024.108630
Přístupová URL adresa: https://pubmed.ncbi.nlm.nih.gov/38906490
https://escholarship.org/content/qt4431z1b6/qt4431z1b6.pdf
https://escholarship.org/uc/item/4431z1b6
Rights: CC BY NC ND
CC BY
Přístupové číslo: edsair.doi.dedup.....13e93e28271d7b493ee81aeef79524db
Databáze: OpenAIRE
Popis
Abstrakt:Infertility affects ∼12 % of couples, with environmental chemical exposure as a potential contributor. Of the chemicals that are actively manufactured, very few are assessed for reproductive health effects. Rodents are commonly used to evaluate reproductive effects, which is both costly and time consuming. Thus, there is a pressing need for rapid methods to test a broader range of chemicals. Here, we developed a strategy to evaluate large numbers of chemicals for reproductive toxicity via a yeast, S. cerevisiae high-throughput assay to assess gametogenesis as a potential new approach method (NAM). By simultaneously assessing chemicals for growth effects, we can distinguish if a chemical affects gametogenesis only, proliferative growth only or both. We identified a well-known mammalian reproductive toxicant, bisphenol A (BPA) and ranked 19 BPA analogs for reproductive harm. By testing mixtures of BPA and its analogs, we found that BPE and 17 β-estradiol each together with BPA showed synergistic effects that worsened reproductive outcome. We examined an additional 179 environmental chemicals including phthalates, pesticides, quaternary ammonium compounds and per- and polyfluoroalkyl substances and found 57 with reproductive effects. Many of the chemicals were found to be strong reproductive toxicants that have yet to be tested in mammals. Chemicals having affect before meiosis I division vs. meiosis II division were identified for 16 gametogenesis-specific chemicals. Finally, we demonstrate that in general yeast reproductive toxicity correlates well with published reproductive toxicity in mammals illustrating the promise of this NAM to quickly assess chemicals to prioritize the evaluation for human reproductive harm.
ISSN:08906238
DOI:10.1016/j.reprotox.2024.108630