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Phthalate exposure, diet effect modification and human reproductive health

Award Number: R01ES038742
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: 08/25/2026
PERIOD OF PERFORMANCE END DATE: 08/24/2030

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Phthalate exposure, diet effect modification and human reproductive health - PROJECT SUMMARY General population has little control on phthalate exposure, which is ubiquitous. Adverse reproductive effects for exposure to phthalates have been well documented in animals and humans. Experimental work showed that administration of certain carotenoids significantly attenuated phthalate-induced gonadotoxicity. Similarly, an interaction between long-chain n-3 polyunsaturated fatty acids (n3PUFA) and phthalate metabolites may be possible since they both can bind to human peroxisome proliferator-activated receptors (PPARs). Despite the biological plausibility, demonstrated interactions for different diseases or biological processes, and studies showing the main effects of serum n3PUFA on success rates among women undergoing infertility treatment, little is known on whether serum carotenoids or n3PUFA can modify the adverse reproductive effects of phthalates. To address this important knowledge gap, we propose to evaluate the associations of urinary phthalate metabolite concentrations (individually and as a mixture) and effect modification by serum n3PUFA and carotenoids with markers of ovarian reserve (aim 1), semen parameters (aim 2) and pregnancy and perinatal endpoints (aim 3). We will leverage data and biological samples from the Environment and Reproductive Health (EARTH) Study, a prospective preconception cohort of couples recruited from a fertility clinic and followed through delivery, in which urine, serum and semen samples have already been collected along with clinical data on pregnancy and perinatal outcomes of couples who have conceived during the study. By taking advantage of this unique resource, we will be able to address these important questions in a time- and cost-efficient manner. Results of the proposed study will increase our understanding of how diet-phthalate interactions can influence human reproduction with clear implications for the clinical management of infertility. Both supplemental n3PUFA and carotenoids are very low cost and available as both over the counter. Advising on intake of n3PUFA or carotenoids may be used to protect against the negative reproductive effect of phthalates. This can be useful in clinical practice reducing the burden of infertility by phthalate exposure among the general population and improving treatment outcomes among subfertile couples.


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 = $4,061,969 )
2026	2026	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90033	LOS ANGELES	USA	Environmental Health	000	1	8/19/2026	NEW	$4,061,969
														Subtotal = $4,061,969

Grand Total All Awards = $4,061,969

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Phthalate exposure, diet effect modification and human reproductive health

Award Number: R01ES038742

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: 08/25/2026

PERIOD OF PERFORMANCE END DATE: 08/24/2030

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