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

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.