Cross-Tissue Molecular Responses in the Liver and Blood After Toxicant Exposures

Authors

• Bo Zhang
• Benpeng Miao
• Shuhua Fu
• Wanqing Shao
• Cristian Coarfa
• Ravindra Kumar
• Prashant Kuntala
• Bongsoo Park
• Sandra Grimm
• Rahul Jangid
• Laurie Svoboda
• Xiaoyun Xing
• Daofeng Li
• Shaopeng Liu
• Robert Hamanaka
• Claudia Lalancette
• Maureen Sartor
• Christopher Krapp
• Gregory Crawford
• Heather Patisaul
• Tim Wiltshire
• Shyam Biswal
• Gokhan Mutlu
• Sanjay Rajagopalan
• Wan-Yee Tang
• Marisa Bartolomei
• Cheryl Walker
• Dana Dolinoy
• Justin Colacino
• David Aylor
• Ting Wang

Language

English

Publication Date

10-10-2025

Journal

Research Square

DOI

10.21203/rs.3.rs-7610132/v1

PMID

41282178

PMCID

PMC12632707

PubMedCentral® Posted Date

10-10-2025

PubMedCentral® Full Text Version

Pre-Print

Abstract

Exposure to toxic substances, particularly early in life, can perturb epigenomic marks linked to disease susceptibility. Human studies of environmental exposures often rely on surrogate tissues such as blood, but toxicant accumulation differs across organs and results in tissue-specific responses. Thus, understanding whether exposure-induced epigenomic alterations in surrogate tissues such as blood reflect changes in toxicant target tissues, such as liver, is essential for designing and interpreting environmental epigenetic studies. To address this knowledge gap, we systematically analyzed 1,013 multi-omics data from the TaRGET II Consortium, comparing molecular responses in mouse liver and blood following perinatal exposure to arsenic, lead, bisphenol A, tributyltin, di-2-ethylhexyl phthalate, tetrachlorodibenzo-p-dioxin, or air pollution in the form of particulate matter < 2.5μm (PM2.5). Most toxicant-induced molecular changes were tissue-specific, yet we identified a subset of co-regulated genes and regulatory elements in liver and blood in response to early-life exposure to toxicants. Moreover, we discovered that specific pathways, such as immune-related processes, were commonly affected by exposures in both tissues, and transcription factors, including Klf, Jun, Ets1, and Cebp, emerged as shared regulators. While molecular alterations are infrequently conserved between tissues following toxicant exposure, the shared alterations in transcription factors and biological pathways may provide a strategy to link effects in surrogate tissues to target tissues.

Keywords

Environmental epigenetics, surrogate and target tissue, transcriptome, epigenetic biomarkers, TaRGET II Consortium, early-life exposure

Published Open-Access

yes

Recommended Citation

Zhang, Bo; Miao, Benpeng; Fu, Shuhua; et al., "Cross-Tissue Molecular Responses in the Liver and Blood After Toxicant Exposures" (2025). Faculty, Staff and Students Publications. 8311.
https://digitalcommons.library.tmc.edu/baylor_docs/8311