Deoxynivalenol Disrupts Male Mice Reproduction through Gut-Testis Axis Dysregulation and Metabolic Alterations

Abstract

The mycotoxin deoxynivalenol (DON) is a widespread contaminant that threatens male reproductive health, though the systemic mechanisms involving the gut-testis axis remain incompletely understood. We employed a multi-omics approach-integrating transcriptomics, 16S rRNA sequencing, and serum metabolomics-in a mouse model to investigate these mechanisms. Oral exposure to DON (2 mg/kg/day for two weeks) induced testicular damage and disrupted the blood-testis barrier, marked by the downregulation of Occludin and GJA1, alongside the suppression of steroidogenesis-related genes and proteins including StAR and CYP17A1. Concurrently, DON triggered gut microbiota dysbiosis, characterized by an increased abundance of Desulfovibrio and a decline in beneficial bacteria. Serum metabolomics further identified a significant depletion of key fatty acids and the cholesterol precursor 5Alpha-Cholestanol. Crucially, fecal microbiota transplantation from DON-treated mice reproduced testicular damage and suppressed steroidogenesis in recipient animals, directly establishing the causal role of gut microbiota in DON-induced reproductive toxicity. These findings collectively demonstrate that DON impairs male reproductive function by inducing gut microbiota dysbiosis and associated metabolic alterations. This work advances our understanding of the gut-testis axis in toxicology and provides mechanistic insights for mitigating mycotoxin-induced reproductive dysfunction.

Keywords: Deoxynivalenol; fatty acid; spermatogenesis; steroid hormone.