6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure
OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2023-04-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866123001073/type/journal_article |
| _version_ | 1797840395079516160 |
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| author | Sarah McLarnan Allison Kupsco Tessa Bloomquist Kathryn DeSantis Julie Herbstman Brandon Pearson |
| author_facet | Sarah McLarnan Allison Kupsco Tessa Bloomquist Kathryn DeSantis Julie Herbstman Brandon Pearson |
| author_sort | Sarah McLarnan |
| collection | DOAJ |
| description | OBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design. |
| first_indexed | 2024-04-09T16:14:24Z |
| format | Article |
| id | doaj.art-3a53513a31cf4dd2aa77496d8da95aa0 |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-09T16:14:24Z |
| publishDate | 2023-04-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-3a53513a31cf4dd2aa77496d8da95aa02023-04-24T05:55:56ZengCambridge University PressJournal of Clinical and Translational Science2059-86612023-04-0172210.1017/cts.2023.1076 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH ExposureSarah McLarnan0Allison Kupsco1Tessa Bloomquist2Kathryn DeSantis3Julie Herbstman4Brandon Pearson5Mailman School of Public Health, Columbia UniversityMailman School of Public Health, Columbia UniversityMailman School of Public Health, Columbia UniversityMailman School of Public Health, Columbia UniversityMailman School of Public Health, Columbia UniversityMailman School of Public Health, Columbia UniversityOBJECTIVES/GOALS: This study models a framework for integrating epidemiological and experimental approaches to investigate the effect of prenatal polycyclic aromatic hydrocarbon (PAH) exposure on mitochondrial function (mtDNAcn, superoxide production and membrane potential) as a potential mechanism of toxicity. METHODS/STUDY POPULATION: The epidemiological aim of this study characterizes mitochondrial outcomes in samples of umbilical cord tissue and blood from two Manhattan based birth cohorts. Prenatal PAH exposure is quantified using silicone wristbands worn for 48 hours during the third trimester of pregnancy. Experimentally, we are applying a PAH mixture designed to emulate the exposure profile of the human cohorts to mouse preimplantation embryos on various dosing schedules and quantifying the same mitochondrial outcomes. mtDNAcn is quantified using rtPCR while superoxide production and membrane potential are measured using fluorescence microscopy. The goal of this study design is to leverage the strengths of each approach to draw more robust conclusions than could be derived from either alone. RESULTS/ANTICIPATED RESULTS: Preliminary results of this study have found associations between higher levels of PAH exposure and increased mitochondrial superoxide production and hyperpolarization of the mitochondrial membrane potential in mouse preimplantation embryos. We anticipate these findings to persist across dosing schedules. We furthermore expect a decrease in mtDNAcn in association with higher PAH exposure in umbilical cord tissue samples and decreased mtDNAcn with exposure to the PAH mixture in mouse embryos. DISCUSSION/SIGNIFICANCE: Characterizing the effect of prenatal PAH exposure on the mitochondria is a critical step in understanding the mechanisms that underlie the toxicity of this exposure. By employing a similar exposure mixture and mitochondrial outcomes across epidemiological and experimental approaches, we offer a model of true interdisciplinary research design.https://www.cambridge.org/core/product/identifier/S2059866123001073/type/journal_article |
| spellingShingle | Sarah McLarnan Allison Kupsco Tessa Bloomquist Kathryn DeSantis Julie Herbstman Brandon Pearson 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure Journal of Clinical and Translational Science |
| title | 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure |
| title_full | 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure |
| title_fullStr | 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure |
| title_full_unstemmed | 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure |
| title_short | 6 An Interdisciplinary Approach to Studying the Mitochondrial Toxicity of Prenatal PAH Exposure |
| title_sort | 6 an interdisciplinary approach to studying the mitochondrial toxicity of prenatal pah exposure |
| url | https://www.cambridge.org/core/product/identifier/S2059866123001073/type/journal_article |
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