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Toxic effects of trichloroethylene and its metabolite on placental cells at the maternal-fetal interface

Award Number: K01ES036552
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/20/2024
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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Toxic effects of trichloroethylene and its metabolite on placental cells at the maternal-fetal interface - PROJECT SUMMARY/ABSTRACT Adverse birth outcomes are prevalent conditions that increase the risk of morbidity and mortality during infancy and the development of chronic metabolic diseases in adulthood. Despite being multifactorial in nature, the causes of adverse birth outcomes, particularly concerning placental dysfunction, are not well understood. Maternal exposure to environmental contaminants is believed to contribute to these outcomes. As a reproductive toxicologist, Dr. Elkin's research seeks to understand the role that maternal exposure to environmental contaminants play in contributing to adverse birth outcomes involving placental dysfunction, and to identify mechanisms by which these aberrant effects can be mitigated or prevented. This Transition to Independent Environmental Health Research (TIEHR) Care Award will provide Dr. Elkin the opportunity to increase training and experience to meet: 1) research development goals, including utilization of single-nucleus technologies and establishment of an in vitro model to represent the syncytial barrier at the maternal-fetal interface, and 2) professional development goals, including science communication, mentoring, and management skills. In humans, maternal exposure to the industrial solvent trichloroethylene is associated with increased risk of low birth weight and restricted fetal growth, conditions linked to placental dysfunction. For the research component of this project, Dr. Elkin will investigate the biological mechanisms of the trichloroethylene metabolite S-(1,2-dichlorovinyl)-L-cysteine (DCVC) contributing to restricted fetal growth by identifying molecular factors underpinning disruption of placental function at the maternal-fetal interface. At the maternal- fetal interface, several different cell types of trophoblast lineage have critical functions. Previously, Dr. Elkin extensively characterized the effects of DCVC on HTR-8/SVneo cells, which model invasive extravillous trophoblasts. Nevertheless, toxic effects on other important cell types at the maternal-fetal interface have not been explored. Recently, Dr. Elkin's colleagues published promising preliminary data showing that DCVC caused aberrant apoptosis, oxidative stress and inflammation in differentiated BeWo cells, a cell line that models the interhaemal barrier of multinucleated syncytiotrophoblasts separating maternal and fetal circulations. Using an in vitro approach, Dr. Elkin's project will expand on compelling preliminary data by: (1) identifying other placental cell types vulnerable to DCVC at the maternal fetal interface using single-nucleus RNA-sequencing (2) examining DCVC effects on mitochondrial energetics of differentiated syncytiotrophoblasts and (3) determining if DCVC affects placental villous barrier function. The proposed research will address the NIEHS goal of “advancing scientific understanding of the role that early exposure to environmental contaminants play in impacting disease risk later in life.” The findings will inform various stakeholders including lawmakers tasked with protecting the public and clinicians developing therapeutic interventions to combat elevated risk of untoward complications, ultimately improving maternal/fetal outcomes.


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 = $176,243 )
2026	2026	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Environmental Health	000	3	6/19/2026	NON-COMPETING CONTINUATION	$176,243
														Subtotal = $176,243

Issue Date FY: 2025 ( Subtotal = $175,746 )
2025	2025	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Environmental Health	000	2	6/16/2025	NON-COMPETING CONTINUATION	$175,746
														Subtotal = $175,746

Issue Date FY: 2024 ( Subtotal = $176,270 )
2024	2024	SAN DIEGO STATE UNIVERSITY FOUNDATION	5250 CAMPANILE DR	SAN DIEGO	CA	92182	SAN DIEGO	USA	Environmental Health	000	1	7/19/2024	NEW	$176,270
														Subtotal = $176,270

Grand Total All Awards = $528,259

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Toxic effects of trichloroethylene and its metabolite on placental cells at the maternal-fetal interface

Award Number: K01ES036552

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/20/2024

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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