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HERITABLE, EPIGENETIC EFFECTS OF PATERNAL ALCOHOL USE ON FASD PHENOTYPES

Award Number: R01AA028219
ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 05/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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HERITABLE, EPIGENETIC EFFECTS OF PATERNAL ALCOHOL USE ON FASD PHENOTYPES - Project Summary & Abstract PROJECT SUMMARY & ABSTRACT Despite evidence that poor paternal health increases the risk of pregnancy loss and that maternal alcohol use correlates with paternal drinking, all public health messaging addressing fetal alcohol spectrum disorders (FASDs) exclusively targets women. The Golding lab and other researchers examining paternal epigenetic effects propose that the exclusive emphasis on maternal health has created a significant blind spot in our efforts to understand the origins of FASDs and that paternal drinking is an entirely unexplored source of variation in alcohol-related birth defect penetrance and severity. Published preclinical studies from the Golding lab demonstrate that chronic preconception male alcohol exposures cause dose-dependent effects on offspring fetoplacental growth and craniofacial patterning. Emerging research reveals that these effects on offspring development arise as part of a heritable response to paternal oxidative stress, promoting the epigenetic inheritance of mitochondrial dysfunction. The offspring of alcohol-exposed fathers exhibit deficits in mitochondrial function, including alterations in mitochondrial structure, increased inflammatory cytokines, a reduced NAD+/NAHD ratio, and increased mitophagy, the removal of damaged mitochondria. Notably, these deficits interact with maternal alcohol exposures to exacerbate FASD outcomes and persist into adulthood. Individuals diagnosed with FASDs exhibit an increased incidence of age-related diseases and a reduced life expectancy. This proposal posits that some FASD adverse health outcomes are linked to paternal epigenetic effects on mitochondrial health. This proposal will test the hypothesis that paternal systemic mitochondrial stress induced by chronic alcohol exposure alters sperm-inherited noncoding RNAs, which provoke lasting epigenetic changes in offspring mitochondrial function and the emergence of FASD outcomes. The research outlined in this proposal will use transgenic mouse models to exacerbate and track the epigenetic transmission of mitochondrial dysfunction from parents to offspring, through fetal life and into adulthood. Published studies from the Golding lab demonstrate that chronic male alcohol use induces mitochondrial stress in the liver and epididymis – the portion of the male reproductive tract where sperm mature. This paternal mitochondrial stress correlates with the enrichment of sperm-inherited microRNAs, influencing the antioxidant response and mitochondrial function. This proposal will determine the function of these sperm-inherited noncoding RNAs and their relationship to the emergence of FASD phenotypes. Maternal education on the benefits of dietary folic acid intake and the dangers of drug use during pregnancy has helped significantly increase children's health. However, 50% of the information necessary to optimize the chances of achieving a healthy pregnancy may be missing because the father's lifestyle choices are not deemed important. The research outlined in this grant proposal will address this knowledge gap.


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 = $607,064 )
2026	2026	TEXAS A&M AGRILIFE RESEARCH	2147 TAMU	COLLEGE STATION	TX	77843	BRAZOS	USA	Alcohol Research Programs	000	6	4/29/2026	COMPETING CONTINUATION	$607,064
														Subtotal = $607,064

Issue Date FY: 2024 ( Subtotal = $329,679 )
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	001	5	5/21/2024	NON-COMPETING CONTINUATION	$32,967
2024	2024	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	000	5	3/25/2024	NON-COMPETING CONTINUATION	$296,712
														Subtotal = $329,679

Issue Date FY: 2023 ( Subtotal = $330,212 )
2023	2023	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	000	4	3/16/2023	NON-COMPETING CONTINUATION	$330,212
														Subtotal = $330,212

Issue Date FY: 2022 ( Subtotal = $330,720 )
2022	2022	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	000	3	3/29/2022	NON-COMPETING CONTINUATION	$330,720
														Subtotal = $330,720

Issue Date FY: 2021 ( Subtotal = $331,204 )
2021	2021	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	000	2	3/22/2021	NON-COMPETING CONTINUATION	$331,204
														Subtotal = $331,204

Issue Date FY: 2020 ( Subtotal = $330,888 )
2020	2020	TEXAS A & M UNIVERSITY	400 HARVEY MITCHELL PKY S STE 300	COLLEGE STATION	TX	77845	BRAZOS	USA	Alcohol Research Programs	000	1	6/17/2020	NEW	$330,888
														Subtotal = $330,888

Grand Total All Awards = $2,259,767

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HERITABLE, EPIGENETIC EFFECTS OF PATERNAL ALCOHOL USE ON FASD PHENOTYPES

Award Number: R01AA028219

ORGANIZATION: NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 05/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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