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Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals

Award Number: R01ES030722
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: 11/01/2021
PERIOD OF PERFORMANCE END DATE: 10/31/2026

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Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals - PROJECT SUMMARY A single toxicant exposure during development can produce reproductive defects in adulthood and subsequent generations, presenting a major hurdle in the prevention and treatment of human infertility. Despite its significance, however, the mechanisms that mediate this process are poorly understood. Endocrine disrupting chemicals (EDCs) play a role in the increasing incidence of male infertility worldwide, and mounting evidence suggests that EDC exposure can alter gene expression and the epigenome. Our long-term goal is to determine how environmental toxicants interfere with reproductive health so that evidence-based strategies to prevent and treat adult-onset and transgenerational disease can be developed.!The overall objective for this NIEHS R01 Award (PA-19-056) application is to determine genome function alterations and epigenetic regulation of environmentally-influenced infertility. The central hypothesis is that sublethal EDC exposure during male gonad development leads to genomic and epigenetic dysregulation that alters testicular mitochondrial function in exposed generation and subsequent generations. The rationale for the proposed research is that investigation of the mechanisms underlying EDC induced infertility will advance prevention, risk-assessment, diagnostic, and treatment strategies for human male infertility. Guided by strong preliminary data, this hypothesis will be tested by pursuing three specific aims: 1) Determine testicular cell-type specific and life stage specific changes in genome function to identify critical windows for biomarkers of effect and gene relationships; 2) Identify changes in the epigenome related to phenotypic and genetic endpoints; 3) Determine multigenerational and transgenerational cell-specific transcriptomic and epigenetic changes induced by ancestral exposure. Ultimately, these results will identify critical windows for biomarkers of effect, inform the interplay among pathways mediating toxic endpoints.


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	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	000	5	11/26/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2025 ( Subtotal = $311,752 )
2025	2025	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	000	5	10/29/2024	NON-COMPETING CONTINUATION	$311,752
														Subtotal = $311,752

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	000	4	12/13/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $449,630 )
2023	2023	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	000	4	10/31/2022	NON-COMPETING CONTINUATION	$449,630
														Subtotal = $449,630

Issue Date FY: 2022 ( Subtotal = $529,891 )
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	001	3	10/28/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$529,891
2022	2022	UNIVERSITY OF FLORIDA	1523 UNION RD RM 207	GAINESVILLE	FL	32611	ALACHUA	USA	Environmental Health	003	3	4/5/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$428,161
2022	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	2	10/25/2021	NON-COMPETING CONTINUATION	$0
2022	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	002	2	4/5/2022	NON-COMPETING CONTINUATION	-$428,161
														Subtotal = $529,891

Issue Date FY: 2021 ( Subtotal = $493,681 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	2	10/28/2020	NON-COMPETING CONTINUATION	$493,681
														Subtotal = $493,681

Issue Date FY: 2020 ( Subtotal = $351,876 )
2020	2020	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	1	12/19/2019	NEW	$351,876
														Subtotal = $351,876

Grand Total All Awards = $2,136,830

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Genetic and epigenetic mechanisms of infertility caused by endocrine disrupting chemicals

Award Number: R01ES030722

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: 11/01/2021

PERIOD OF PERFORMANCE END DATE: 10/31/2026

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