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Parental Co-Exposure to Methylmercury and Inorganic Arsenic in Zebrafish (Danio rerio): Metabolism and Offspring Behavior

Award Number: R21ES033753
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2022
PERIOD OF PERFORMANCE END DATE: 08/31/2025

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Parental Co-Exposure to Methylmercury and Inorganic Arsenic in Zebrafish (Danio rerio): Metabolism and Offspring Behavior - Summary Methylmercury (MeHg) is a potent neurotoxin, and recent studies indicate that inorganic arsenic(III) (iAs) is also neurotoxic. Although chemicals co-occur in the environment, the study of chemical mixtures is more recent. Heavy metals target the central nervous system, and co-exposure may result in synergistic neurotoxic impacts. However, the biological and molecular mechanisms underlying these joint effects are uncertain. The aim of our study is to investigate synergism between iAs and MeHg, using the zebrafish (Danio rerio) model system. Aim 1. Investigate the uptake and metabolism of iAs and MeHg in zebrafish. We anticipate that co-exposure to both chemicals will alter the proportion of arsenic species in the liver, compared to controls. Adult zebrafish will be exposed to environmentally relevant levels of MeHg (through diet) and sodium arsenite (through water) (six treatment groups). In the liver, mercury species and arsenic species will be compared between treatment groups, and sex-specific differences will be investigated. Accumulation of mercury and arsenic in adult tissues and organs will be visualized using laser ablation-ICP-MS. Aim 2. Determine the impacts of MeHg and iAs exposure in progeny, including neurobehavioral outcomes, and mechanisms of toxicity. Mercury and arsenic species will be determined in whole embryos [120 hours post fertilization (hpf)], exposed to both neurotoxicants through maternal transfer. In embryos (6-120 hpf) and adults [90 days post fertilization (dpf)], morphological and neurobehavioral endpoints will be assessed. Using RNA sequencing, we will conduct genome-wide transcriptomics of offspring brains (90 dpf), and identify signaling pathways, which are enriched or depleted due to co-exposure. Transcriptomic results will be compared between treatment groups and males/females. This study will advance our understanding of the mechanisms by which co-exposure to two chemicals, which frequently co-occur in the environment, contribute synergistically to offspring neurotoxicity.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2022	OREGON STATE UNIVERSITY	1500 SW JEFFERSON AVE	CORVALLIS	OR	97331	BENTON	USA	Environmental Health	000	1	1/28/2026	NEW	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	OREGON STATE UNIVERSITY	1500 SW JEFFERSON AVE	CORVALLIS	OR	97331	BENTON	USA	Environmental Health	000	1	7/31/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $392,682 )
2022	2022	OREGON STATE UNIVERSITY	1500 SW JEFFERSON ST	CORVALLIS	OR	97331	BENTON	USA	Environmental Health	000	1	9/10/2022	NEW	$392,682
														Subtotal = $392,682

Grand Total All Awards = $392,682

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Parental Co-Exposure to Methylmercury and Inorganic Arsenic in Zebrafish (Danio rerio): Metabolism and Offspring Behavior

Award Number: R21ES033753

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2022

PERIOD OF PERFORMANCE END DATE: 08/31/2025

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