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Exposure to Ambient Air Pollution and Temperature During Spermatogenesis: Impact on Men's Reproductive Health and Infertility Treatment Outcomes

Award Number: K01ES034005
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 05/04/2022
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Exposure to Ambient Air Pollution and Temperature During Spermatogenesis: Impact on Men's Reproductive Health and Infertility Treatment Outcomes - PROJECT SUMMARY/ABSTRACT Approximately 12% of couples in the United States seek infertility treatment, which for some is associated with treatment-related side-effects, treatment-related stressors, and a significant financial burden. Although male- factor infertility contributes to an estimated 30-50% of cases of couple infertility, risk factors, mechanisms, and potential interventions for male-factor infertility have been critically understudied. Ambient air pollution and ambient temperature extremes are ubiquitous exposures associated with systemic inflammation and oxidative stress, to which the process of spermatogenesis may be uniquely susceptible. Research has found exposure to high levels of air pollution may adversely impact semen quality; however, the effect of exposure during developmentally-sensitive windows of spermatogenesis on semen quality, impacts on sperm epigenetic factors including DNA methylation, and the cumulative impact of male partner exposure on infertility treatment outcomes have been little evaluated. This study will utilize data from the Folic Acid and Zinc Supplementation Trial (FAZST) to estimate impacts of ambient environmental factors on male fertility, adding estimates of individual exposure to ambient air pollution and temperature. Adding to sparse literature from countries with low-to-moderate levels of air pollution, this study will evaluate exposure to air pollution and high and low ambient temperatures during developmentally susceptible windows of spermatogenesis (mitosis, meiosis, spermiogenesis, and spermiation) with semen quality, leveraging four repeated semen samples from more than 1,900 participants (Aim 1). Epigenetic alterations in sperm are increasingly recognized as a potential mechanism impacting male fertility, with exposure to several oxidative stress-inducing and endocrine- disrupting environmental factors linked to differential DNA methylation in sperm. This study will conduct a novel assessment of the impact of ambient air pollution exposure on sperm DNA methylation (Aim 2). Finally, this study will utilize information on outcomes of infertility treatment cycles (in vitro fertilization and intrauterine insemination cycles) and timing of treatment-related semen samples to evaluate the impact of male partner exposure to air pollution and ambient temperature during spermatogenesis on probability of pregnancy during infertility treatment, accounting for exposure windows during embryogenesis and implantation (Aim 3). This career development award will extend the candidate’s prior training and research experience in environmental and reproductive epidemiology by providing expert mentoring and targeted training in epigenetics, air quality exposure assessment, and causal inference. Her primary mentor Dr. Richard Pilsner (epigenetics), along with members of her mentoring team Dr. Timothy Canty (air quality modeling) and Dr. Laura Balzer (causal inference), with provide the needed mentoring for the candidate to establish a productive independent research program. In addition to targeted training, this K01 award will add novel evidence for the impact of ambient air pollution and temperature on men’s reproductive health and outcomes of infertility treatment.


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: 2024 ( Subtotal = $145,787 )
2024	2024	UNIVERSITY OF MASSACHUSETTS	101 COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	3	4/17/2024	NON-COMPETING CONTINUATION	$145,787
														Subtotal = $145,787

Issue Date FY: 2023 ( Subtotal = $147,748 )
2023	2023	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	2	4/20/2023	NON-COMPETING CONTINUATION	$147,748
														Subtotal = $147,748

Issue Date FY: 2022 ( Subtotal = $144,004 )
2022	2022	UNIVERSITY OF MASSACHUSETTS	COMMONWEALTH AVE	AMHERST	MA	01003	HAMPSHIRE	USA	Environmental Health	000	1	5/4/2022	NEW	$144,004
														Subtotal = $144,004

Grand Total All Awards = $437,539

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Exposure to Ambient Air Pollution and Temperature During Spermatogenesis: Impact on Men's Reproductive Health and Infertility Treatment Outcomes

Award Number: K01ES034005

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 05/04/2022

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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