Environmental Benzene Exposure Induces a Conserved Neutrophil Degranulation Program Across Species.

Area of Science:

• Environmental toxicology
• Developmental biology
• Immunology

Background:

• Environmental exposures during development can disrupt immune regulatory networks.
• Benzene is a common contaminant linked to immune dysregulation, but its developmental effects are unclear.
• Conserved immune defense mechanisms exist across diverse organisms.

Purpose of the Study:

• To investigate conserved cross-species immune regulatory pathways affected by benzene exposure during development.
• To characterize transcriptional responses to low-level benzene exposure in human, murine, and zebrafish developmental models.

Main Methods:

• Comparative transcriptomic analysis using bulk RNA sequencing on human placenta, murine placenta, and zebrafish larvae.
• Analysis of benzene exposure in experimental models (≤5 ppm) and benzene adducts in human maternal plasma.
• Stratification of murine data by fetal sex and pathway/network analyses to identify conserved responses.

Main Results:

• Benzene exposure consistently activated innate immune pathways, including neutrophil degranulation and IL-8 signaling.
• Rho GTPase-mediated inflammatory responses were identified as a conserved reaction.
• CXCL8 and ERK1/2 emerged as shared regulatory hubs across species.

Conclusions:

• Benzene exposure during vertebrate development elicits a conserved innate immune signature.
• Environmental chemical perturbations can disrupt fundamental, evolutionarily conserved immune regulatory programs.
• Findings highlight potential cross-species impacts of environmental contaminants on immune development.