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Effects of Preconception Phthalate Exposure on Implantation and Placentation

Award Number: K01ES038947
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 08/20/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2029

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Effects of Preconception Phthalate Exposure on Implantation and Placentation - Project Summary Worldwide, the incidence of human infertility, reproductive disorders, and pregnancy complications are on the rise. Now more than ever, humans are exposed to endocrine-disrupting chemicals (EDCs), agents that interfere with hormone action in the body, which have been shown to contribute to the risk for infertility and reduce fecundity. To date, mechanistic understanding of reproductive susceptibility to EDCs has primarily focused on exposure during gestation and postnatal development. There remains a significant knowledge gap about the physiological consequences of EDC exposure on female reproductive tissues during the preconception window between puberty and pregnancy. During this window, cyclical hormonal events dictate the tissue remodeling required to facilitate interactions between the embryo and the lining of the uterus. The steroid hormones estrogen (E2) and progesterone (P4) are the master regulators that mediate these modifications, initiating a temporary window of receptivity during which the embryo can undergo implantation and initiate placenta development. The scientific objective of this proposal is to elucidate the mechanisms by which preconception EDC exposure can impact adaptations in the maternal reproductive system that facilitate implantation and placentation. Phthalates are known endocrine disruptors that have been shown to disrupt E2 and P4 and are of particular concern for women’s reproductive health due to their prevalence in personal care, beauty, and feminine hygiene products. Moreover, between puberty and pregnancy, exposure to phthalates is likely to increase concurrently with the use of cosmetics and feminine hygiene products. To date, only a few studies have investigated the impact of phthalates on implantation outcomes. However, these studies focused on exposure at the time of implantation. We hypothesize that preconception phthalate exposure disrupts endometrial receptivity and blastocyst implantation by altering peri-implantation E2 and P4 signaling. We further hypothesize that phthalate-induced aberrations in implantation will lead to placental abnormalities and reduce offspring viability. We aim to do this using the following specific aims: 1) measure functional changes in peri- implantation uterine remodeling and receptivity following preconception phthalate exposure, 2) identify the mechanisms by which preconception phthalate exposure disrupts blastocyst adhesion and invasion, and 3) evaluate the long-term impacts of preconception phthalate exposure on placental development and function, and fetal viability. Completing these aims will help fill an important knowledge gap about the role of preconception endocrine disruption on female fertility and fecundity. The training objective of this proposal is to complement the PI’s background in reproductive toxicology, bioinformatics, experimental, and career development skills. In conjunction with the mentoring team and institutional environment, this proposal will provide the candidate with the scientific skills and career mentorship to independently lead a translational research program in reproductive toxicology to improve human 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: 2026 ( Subtotal = $167,562 )
2026	2026	CLEMSON UNIVERSITY	201 SIKES HALL	CLEMSON	SC	29634	PICKENS	USA	Environmental Health	000	1	8/20/2026	NEW	$167,562
														Subtotal = $167,562

Grand Total All Awards = $167,562

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Effects of Preconception Phthalate Exposure on Implantation and Placentation

Award Number: K01ES038947

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 08/20/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2029

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