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Paternal exposures, sperm epigenetic marks, and autism spectrum disorder in offspring

Award Number: K99ES035433
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 06/07/2024
PERIOD OF PERFORMANCE END DATE: 05/31/2026

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Paternal exposures, sperm epigenetic marks, and autism spectrum disorder in offspring - Abstract Research on environmental risk factors for autism spectrum disorder (ASD) has largely focused on maternal gestational exposures and on exposures in the early postnatal period. The possibility that paternal preconception factors play important etiological roles in the disorder has not been extensively studied. A possible role for paternal factors in ASD is suggested based on the consistently robust associations observed between ASD and paternal age. In addition, ASD has been associated with alterations in epigenetic marks and related gene expression across several somatic tissues, suggesting that one possible etiologic mechanism could be through effects on sperm epigenetic imprinting. Exposure to ambient air pollution has been associated in animal studies with alteration in sperm epigenetic marks that can be transmitted to offspring and affect phenotype. Human data has also linked exposure to air pollution, certain comorbidities, and use of some medications with reduced sperm quality parameters, possibly due to inheritable epigenetic effects. My aim in the proposed work is to evaluate the role of paternal factors in the etiology of ASD. Specifically, I will evaluate whether exposure to air pollution during the spermatogenesis period preceding a conception is associated with an increased risk of autism in the offspring (aim 1); whether paternal comorbidities and their pharmacologic treatments have additive or synergistic effects with air pollution on ASD risk given that similar biologic pathways have been implicated in these different sets of exposures (aim 2); and whether exposure to air pollution causes DNA methylation changes in sperm overall and specifically in ASD related loci, which will inform mechanistic pathways (aim 3). For these goals, I will use data from a large Israeli birth cohort of nearly half a million children with detailed demographic and clinical information, and will also collect semen biospecimens from subgroup of men attending a large IVF clinic. Air pollution exposure will be estimated using state-of-the-art satellite-derived air pollution exposure models based on geocoded residential addresses. The proposed work will make novel translational and mechanistic contributions to ASD through identification of specific paternal factors and biological pathways that cause, exacerbate, or mediate ASD risk. Findings stemming from the proposed work will help guide interventions to reduce exposure to harmful environmental toxicants or attenuate their downstream effects. In addition to the research goals, the proposed work has a strong training component in epigenetic and pharmacologic epidemiology and in statistical genomics that would substantially advance my skillset in using innovative study designs and analytic approaches in exposomic research of heterogenous risk factors for neurodevelopmental disorders using observational data. The proposed training and mentoring will be instrumental for advancing my goal of becoming an independent researcher in the field of environmental neuroepidemiology and precision environmental health.


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	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	000	2	5/18/2026	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $92,887 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	1033 MASSACHUSETTS AVE STE 3	CAMBRIDGE	MA	02138	MIDDLESEX	USA	Environmental Health	000	2	7/15/2025	NON-COMPETING CONTINUATION	$92,887
														Subtotal = $92,887

Issue Date FY: 2024 ( Subtotal = $92,854 )
2024	2024	HARVARD COLLEGE PRESIDENT & FELLOWS OF	677 HUNTINGTON AVE	BOSTON	MA	02115	SUFFOLK	USA	Environmental Health	000	1	6/4/2024	NEW	$92,854
														Subtotal = $92,854

Grand Total All Awards = $185,741

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Paternal exposures, sperm epigenetic marks, and autism spectrum disorder in offspring

Award Number: K99ES035433

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 06/07/2024

PERIOD OF PERFORMANCE END DATE: 05/31/2026

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