# PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $462,951

## Abstract

Placental tissue is normally discarded at birth, but is essentially a molecular time capsule for
gene by environmental interactions and dysregulated molecular and cellular pathways that
can be revealed at the level of the epigenome. Identifying epigenetic biomarkers at birth that
reflect in utero exposures or predict adverse neurodevelopmental outcomes is an important
goal that has been limited by prior technologies or lack of relevant tissue availability. Our
team of currently collaborating interdisciplinary scientists within the Children’s Center for
Environmental Health plans to use existing placental samples from a prospective high-risk
cohort study (MARBLES) to identify epigenetic biomarkers at birth for in utero exposure to
polychlorinated biphenyls (PCB) and neurodevelopmental outcomes by age three. Using
unbiased whole genome bisulfite sequencing (WGBS), we have previously demonstrated
that placental tissues retain the distinctive DNA methylation patterns of the preimplantation
embryo and so can capture the molecular state in very early development, a feature that is
conserved across mammalian species, including mouse. The new hypothesis to be tested in
this proposal is that perinatal exposures to PCB adversely impact neurodevelopment and
leave a lasting molecular signature over genes relevant to neurodevelopment that can be
detected in placenta. The proposed PCB Epigenomic Brain & Behavior Lasting Effects
Study (PEBBLES) will combine the analysis of human placental samples from the high-risk
MARBLES cohort with the analysis of placenta and brain tissues and sorted cell types
derived from a mouse model of perinatal exposure to the same mixture of PCB congeners
detected in MARBLES mothers. This study will leverage existing neurological and
behavioral analyses and samples to examine the relationship between PCB-induced
perturbations of DNA methylation marks with adverse neurotoxic outcomes. Epigenomic
analyses of placenta and brain as well as sorted cellular subtypes from each of these
tissues will include WGBS for methylome, RNA-seq for transcriptome, and ATAC-seq for
chromatin accessibility. Bioinformatic and statistical analyses will integrate the genomic data
sets with behavioral and molecular outcome measures and determine whether similar
epigenetic marks are observed in placenta that could be used to predict long-lasting adverse
brain and behavioral outcomes in humans.
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## Key facts

- **NIH application ID:** 10416017
- **Project number:** 5R01ES029213-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Janine M LaSalle
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $462,951
- **Award type:** 5
- **Project period:** 2018-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10416017

## Citation

> US National Institutes of Health, RePORTER application 10416017, PCB Epigenomic Brain & Behavior Lasting Effects Study (PEBBLES) (5R01ES029213-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10416017. Licensed CC0.

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