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Dissecting the Role of Lrh1 in Phthalate-Related Reproductive Impairments: A Cellular and Molecular Approach

Award Number: R15ES037124
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: 09/01/2025
PERIOD OF PERFORMANCE END DATE: 08/31/2028

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Dissecting the Role of Lrh1 in Phthalate-Related Reproductive Impairments: A Cellular and Molecular Approach - Project Summary/Abstract The World Health Organization reports that approximately 20% of couples worldwide experience infertility. Phthalates, widely utilized as plasticizers or solvents in a vast array of consumer products, have been implicated in reproductive disturbances, as evidenced by human epidemiological studies and rodent research. This proposal is dedicated to offering comprehensive mentorship and career development in reproductive toxicology research for pre-doctoral health professionals and graduate students. The project is centered on the premise that exposure to phthalates at environmentally relevant concentrations during critical developmental windows for the testis (from embryonic day 15.5 to postnatal day 3) adversely affects spermatogenesis. This is hypothesized to occur through the disruption of Lrh1 signaling in Sertoli cells, crucial for germ cell development. Our approach comprises two innovative aims: The first aims to elucidate how phthalates may impair germ cell development by disrupting Lrh1-mediated regulation of steroidogenesis and metabolism in mouse Sertoli cells. The second seeks to determine the effects of phthalates on the functional capacities of both mouse and human Sertoli cells (using primary cells and cell lines) in vitro by targeting LRH1. The successful completion of these objectives will significantly advance our understanding of the molecular dynamics through which phthalates influence gonadal function and germ cell maturation. Gaining insight into the sex-specific effects of phthalates will facilitate the development of tailored healthcare interventions for diseases related to development, reproduction, and endocrine function. This research, alongside the career development activities proposed, will empower pre-doctoral health professionals and graduate students pursuing careers in healthcare, setting the stage for pivotal breakthroughs in medical science. Ultimately, this project aligns with the National Institute of Environmental Health Sciences (NIEHS) goal to explore the consequences of environmental exposures on human health, marking a critical step forward in environmental and reproductive health research.


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 = $521,992 )
2025	2025	MIDWESTERN UNIVERSITY	19555 N. 59TH AVE ADMINISTRATION BUILDING	GLENDALE	AZ	85308	MARICOPA	USA	Environmental Health	000	1	8/28/2025	NEW	$521,992
														Subtotal = $521,992

Grand Total All Awards = $521,992

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Dissecting the Role of Lrh1 in Phthalate-Related Reproductive Impairments: A Cellular and Molecular Approach

Award Number: R15ES037124

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: 09/01/2025

PERIOD OF PERFORMANCE END DATE: 08/31/2028

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