Grantee Research Project Results
Final Report: Linking Biological Scales Across Generations: An Estuarine and Marine Model for Measuring The Ecological Impact of Endocrine Disrupting Compounds
EPA Grant Number: R835799Title: Linking Biological Scales Across Generations: An Estuarine and Marine Model for Measuring The Ecological Impact of Endocrine Disrupting Compounds
Investigators: Brander, Susanne M , White, J. Wilson , Mehinto, Alvine C , Connon, Richard E
Institution: Oregon State University , Southern California Coastal Water Research Project Authority , University of California - Davis
EPA Project Officer: Aja, Hayley
Project Period: June 1, 2015 through May 31, 2018 (Extended to May 31, 2020)
Project Amount: $399,884
RFA: Systems-Based Research for Evaluating Ecological Impacts of Manufactured Chemicals (2014) RFA Text | Recipients Lists
Research Category: Chemical Safety for Sustainability
Objective:
Many pollutants cause endocrine disruption in aquatic organisms. While studies of the direct effects of toxicants on exposed organisms are commonplace, little is known about the potential for toxicant exposures in a parental (F0) generation to affect unexposed F1 or F2 generations (multigenerational and transgenerational effects, respectively), particularly in estuarine fishes.
Summary/Accomplishments (Outputs/Outcomes):
To investigate this possibility, we exposed Inland silversides (Menidia beryllina) to environmentally relevant (low ng/L) concentrations of ethinylestradiol, bifenthrin, trenbolone, and levonorgestrel from 8 hpf to 21 dph. We then measured development, immune response, reproduction, gene expression, and DNA methylation for two subsequent generations following the exposure. Larval exposure to each compound resulted in negative effects in the F0 and F1 generations, and for ethinylestradiol and levonorgestrel, the F2 also. The specific endpoints that were responsive to exposure in each generation varied, but included increased incidence of larval deformities, reduced larval growth and survival, impaired immune function, skewed sex ratios, ovarian atresia, reduced egg production, and altered gene expression. Additionally, exposed fish exhibited differences in DNA methylation in selected genes, across all three generations, indicating epigenetic transfer of effects. We then assessed DNA methylation patterns for three generations (F0, F1, and F2) in whole body larval fish using reduced representation bisulfite sequencing (RRBS). We found significant (a = 0.05) differences in promoter and/or gene body methylation in treatment fish relative to controls for all EDCs and all generations indicating that both multigenerational (F1) and transgenerational (F2) effects that were caused by strict inheritance of DNA methylation alterations and the dysregulation of epigenetic control mechanisms. Using gene ontology and pathway analyses, we found enrichment in biological processes and pathways representative of growth and development, immune function, reproduction, pigmentation, epigenetic regulation, stress response and repair (including pathways important in carcinogenesis). Further, we found that a subset of potentially EDC responsive genes (EDCRGs) were differentially methylated across all treatments and generations and included hormone receptors, genes involved in steroidogenesis, prostaglandin synthesis, sexual development, DNA methylation, protein metabolism and synthesis, cell signaling, and neurodevelopment. The analysis of EDCRGs provided additional evidence that differential methylation is inherited by the offspring of EDC-treated animals, sometimes in the F2 generation that was never exposed.
Conclusions:
These findings show that low, environmentally relevant levels of EDCs can cause altered methylation in genes that are functionally relevant to impaired phenotypes documented in EDC-exposed animals, that EDC exposure has the potential to affect epigenetic regulation in fish that have not been directly exposed, and suggest that assessments across multiple generations are key to determining the full magnitude of adverse effects from contaminant exposure in early life. Modeling simulations indicate that given empirically observed effects, that all four chemicals would cause significant decline in chronically exposed populations.
Journal Articles on this Report : 2 Displayed | Download in RIS Format
| Other project views: | All 10 publications | 10 publications in selected types | All 10 journal articles |
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Athey S, Albotra S, Gordon C, Monteleone B, Seaton P, Andrady A, Taylor A, Brander S. Trophic transfer of microplastics in an estuarine food chain and the effects of a sorbed legacy pollutant. LETTERS 2020;5(1):154-162 |
R835799 (Final) |
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DeCourten B, Forbes J, Roark H, Burns N, Major K, White J, Li J, Mehinto A, Connon R, Brander S. Multigenerational and Transgenerational Effects of Environmentally Relevant Concentrations of Endocrine Disruptors in an Estuarine Fish Model. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2020;54(21):13849-13860 |
R835799 (Final) |
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Progress and Final Reports:
Original AbstractThe perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.
Project Research Results
- 2018 Progress Report
- 2017 Progress Report
- 2016 Progress Report
- 2015 Progress Report
- Original Abstract
10 journal articles for this project