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Determining how preconception exposure to phthalates impacts sperm function, the epigenome fertility and reproductive outcomes in mice and men

Award Number: R01ES030942
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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SUMMARY Infertility is one of the most common reproductive health disorders affecting 16% of couples in the U.S. Most concerning are the new meta-analysis data showing that sperm counts among men in developed countries have declined over 50% in the past four decades. With no sign of reversing this downward trajectory in the most recent years, we may not only be facing a fertility crisis, but low sperm count has also wider public health implications including increased risks in morbidity and mortality (3, 4). Given this dramatic decrease in sperm quality over a short period, genetic influences are likely not attributable, but rather, environmental factors encountered over the life-course. In particular, phthalates, a class of endocrine disrupting compounds (EDCs) used in plastics and personal care products, are ubiquitous environmental contaminants resulting in widespread human exposure. The ViCTER mechanism provides a unique opportunity to enhance cross-disciplinary and translational research. As such, our research team is poised to determine how paternal preconception phthalates impacts sperm function, the epigenome and early-life development by leveraging ongoing research in mice models (R01: ES028214; PI: Dr. Pilsner) and couples undergoing in vitro fertilization (IVF) as part of the human cohort (Sperm Environmental Epigenetics and Development Study; SEEDS: R01: ES028298; PI: Dr. Pilsner). We hypothesize that a key to understanding how adult exposures to phthalates affects reproductive health lies within sperm epigenetics and physiology. Therefore, our ViCTER objectives are to determine the effects of adult male exposure to phthalates on: 1) small noncoding RNA (sncRNA) in extracellular vesicles (EVs) (Dr. Pilsner); 2) sperm histone methylation (Dr. Kimmins); and 3) sperm capacitation, IVF and embryo development (Dr. Visconti). For our first aim, we will examine the associations of paternal phthalate exposure on sncRNA expression from extracellular vesicles (EVs) of mice and men. Next, we will examine the effect of adult male exposure to phthalates on histone methylation in sperm from mice and men. Finally, we will determine the effect of adult mouse exposure to DEHP, DBP and its mixture on sperm capacitation, acrosome reaction and subsequent embryo development. The proposed research is expected to uncover pathways linking paternal phthalate exposures with adverse reproductive outcomes via sperm physiology and epigenetics. Characterization of potential intermediate pathways between the exposure and outcome continuum is of significant importance because it will inform avenues of translational research for the development of novel approaches to treat and prevent adverse reproductive 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: 2025 ( Subtotal = -$4,477 )
2025	2021	WAYNE STATE UNIVERSITY	5700 CASS AVE STE 4900	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	3	11/20/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$4,477
														Subtotal = -$4,477

Issue Date FY: 2023 ( Subtotal = $0 )
2023	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	000	3	5/5/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $452,638 )
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	001	3	9/15/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$452,638
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	004	3	9/28/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$527,044
2021	2021	WAYNE STATE UNIVERSITY	5057 WOODWARD STE 13001	DETROIT	MI	48202	WAYNE	USA	Environmental Health	002	3	9/25/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2021	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	2	9/13/2021	NON-COMPETING CONTINUATION	$0
2021	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	003	2	9/28/2021	NON-COMPETING CONTINUATION	-$527,044
														Subtotal = $452,638

Issue Date FY: 2020 ( Subtotal = $532,825 )
2020	2020	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	2	6/26/2020	NON-COMPETING CONTINUATION	$532,825
														Subtotal = $532,825

Issue Date FY: 2019 ( Subtotal = $563,082 )
2019	2019	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	1	9/12/2019	NEW	$563,082
														Subtotal = $563,082

Grand Total All Awards = $1,544,068

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Determining how preconception exposure to phthalates impacts sperm function, the epigenome fertility and reproductive outcomes in mice and men

Award Number: R01ES030942

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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