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Reconstructing the Maternal-Fetal Interface: A Placenta–Brain Axis on a Chip Platform to Transform Models of Prenatal Neurotoxicity

Award Number: DP2ES039816
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: 08/26/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Reconstructing the Maternal-Fetal Interface: A Placenta–Brain Axis on a Chip Platform to Transform Models of Prenatal Neurotoxicity - Project Summary: Environmental exposures during pregnancy including pesticides, air pollutants, and common medications are among the most potent yet least understood drivers of adverse neurodevelopment. Epidemiological studies consistently link such exposures to disorders such as autism, ADHD, and schizophrenia, but the mechanistic pathways connecting maternal environment to fetal brain remain a black box. We will address this gap by building the first placenta–brain axis-on-a-chip: a physiologically integrated human co-culture system that couples placental trophoblasts, maternal immune cells, fetal endothelial cells, and cortical organoids via directional microfluidic flow. This platform recreates the maternal-fetal-brain interface in vitro, enabling real-time tracking of how exposures traverse the placental barrier and alter fetal brain development. A defining innovation is the incorporation of next-generation genetically encoded redox biosensors, which allow continuous, cell-type–specific monitoring of oxidative state: a near-universal pathway of vulnerability across diverse toxicants. We hope to determine how maternal exposures alter placental transport and oxidative state in fetal brain organoids; dissect how oxidative stress perturbs neurogenesis, neuronal migration, and circuit assembly; and define predictive “oxidative fingerprints” of vulnerability and resilience across diverse genetic backgrounds, including induced pluripotent stem cell lines from individuals with autism spectrum disorder. Preliminary data demonstrate the feasibility of this approach: we have fabricated perfusable placental barrier chips, validated biosensor integration, and shown oxidative stress responses to paraquat and acetaminophen exposures that correlate with mitochondrial dysfunction and neuronal viability. By resolving the dynamic interplay between maternal exposures, placental physiology, and fetal brain development, this project will transform how we model prenatal neurotoxicity. The knowledge gained will establish mechanistic links between maternal environment and child brain health, inform biomarker discovery, and create a broadly adaptable platform for studying maternal–fetal interactions in development and disease.


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 = $760,000 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Trans-NIH Research Support	000	1	8/26/2026	NEW	$760,000
														Subtotal = $760,000

Grand Total All Awards = $760,000

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Reconstructing the Maternal-Fetal Interface: A Placenta–Brain Axis on a Chip Platform to Transform Models of Prenatal Neurotoxicity

Award Number: DP2ES039816

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: 08/26/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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