# Paternal Zearalenone Exposure Is Associated with Hepatic Dysfunction in F1 Offspring: Insights from Proteomic Analysis

## TL;DR

Paternal exposure to zearalenone causes liver problems in offspring, with proteomic analysis revealing immune and inflammatory pathway disruptions.

## Contribution

This study reveals novel intergenerational effects of paternal zearalenone exposure on offspring liver health and immune pathways.

## Key findings

- F1 offspring of ZEN-exposed fathers developed hepatic steatosis and oxidative stress.
- Proteomic analysis showed dysregulation of NF-κB and chemokine signaling pathways in F1 offspring livers.
- Reduced MHC-I and increased MHC-II levels suggest altered immune responses in affected offspring.

## Abstract

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin that adversely affects directly exposed individuals, yet the intergenerational consequences of paternal ZEN exposure remain poorly understood. In this study, we investigated the impact of paternal ZEN exposure on hepatic outcomes in F1 offspring, with a focus on the underlying molecular mechanisms. Kunming male mice (F0) were fed a ZEN-supplemented diet (10 mg/kg bw/day) for 5 weeks. Their F1 offspring developed hepatic steatosis, elevated oxidative stress, and a chronic inflammatory state. Proteomic analysis of F1 livers revealed significant dysregulation of immune and inflammatory pathways, including NF-κB and chemokine signaling, with reduced MHC-I and increased MHC-II levels. These findings provide mechanistic insight into how paternal ZEN exposure disrupts hepatic immune-metabolic homeostasis in F1 offspring, highlighting a critical and understudied pathway in intergenerational toxicology.