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Inter- and transgenerational effects of paternal arsenic exposure

Award Number: R01ES034768
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: 02/08/2023
PERIOD OF PERFORMANCE END DATE: 11/30/2027

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Inter- and transgenerational effects of paternal arsenic exposure - ABSTRACT/SUMMARY Industrialization had created widespread pollution, which has been steadily declining in developed countries for decades. It is unclear whether and how long-lasting effects of environmental exposure persist across generations and contribute to chronic diseases in later life. Inorganic arsenic (iAs) is the top chemical on the ATSDR priority list of hazardous substances. Here we use iAs as a prototype environmental chemical to dissect the epigenetic inheritance mechanisms in animal models. We focus exclusively on male-lineage exposure to avoid developmental confounding effects due to in utero exposure. We found that the exposure of male mice to iAs in drinking water caused glucose intolerance and upregulated hepatic glucose production in F1 females but not in F1 male offspring. In contrast, paternal iAs decreased liver triglyceride content and circulating free fatty acids levels in F1 males, but not F1 females. F0 sperm and F1 livers display altered DNA methylation and expression in genes related to gonadal hormone signaling and lipid metabolism. In the F2 generation from the male-lineage iAs exposure, mice display reduced adiposity, nutrient malabsorption, and the altered gut microbiome. We hypothesize that the interplay between estrogen receptor, DNA methylation, non-coding RNAs, and gut microbiome accounts for the inter- and transgenerational effects of iAs in metabolic physiology. We will characterize how paternal iAs exposure alters glucose metabolism in F1 female offspring; address how paternal iAs exposure alters lipid metabolism in F1 male offspring, and explore how paternal iAs exposure affects nutrient absorption through altering the gut microbiome in F2 offspring. The mechanistic insights from this study will advance our understanding of the cross-generational effects of environmental exposure on metabolic physiology through the disruption of the endocrine system.


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 = $472,448 )
2026	2026	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Environmental Health	000	4	12/9/2025	NON-COMPETING CONTINUATION	$472,448
														Subtotal = $472,448

Issue Date FY: 2025 ( Subtotal = $472,448 )
2025	2025	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Environmental Health	000	3	12/13/2024	NON-COMPETING CONTINUATION	$472,448
														Subtotal = $472,448

Issue Date FY: 2024 ( Subtotal = $472,448 )
2024	2024	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Environmental Health	000	2	11/17/2023	NON-COMPETING CONTINUATION	$472,448
														Subtotal = $472,448

Issue Date FY: 2023 ( Subtotal = $472,447 )
2023	2023	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	Environmental Health	000	1	2/7/2023	NEW	$472,447
														Subtotal = $472,447

Grand Total All Awards = $1,889,791

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Inter- and transgenerational effects of paternal arsenic exposure

Award Number: R01ES034768

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: 02/08/2023

PERIOD OF PERFORMANCE END DATE: 11/30/2027

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