AFB1 exacerbates testicular and intestinal inflammation by increasing stearoyl ethanolamide and homocysteine levels

In environmental toxicology, aflatoxin B1 (AFB1) is recognized for its detrimental effects on reproductive and intestinal health. This study elucidates how AFB1-induced elevations in stearoyl ethanolamide (SEA) and homocysteine (HCY) impact male fertility and intestinal function in mice. AFB1 was found to markedly reduce sperm concentration and exacerbate sperm damage in mice, primarily by increasing serum SEA and HCY levels. These metabolites compromise testicular structure and function, disrupt the blood-testicular barrier, and downregulate critical testicular proteins including DAZL, SYCP1, SYCP2, StAR, and CYP17A1. Transcriptomic analysis revealed that SEA and HCY broadly alter testicular gene expression, activate NOD-like receptor signaling pathways, induce testicular inflammation, and promote apoptosis. Additionally, SEA and HCY impair intestinal barrier function by reducing the expression of tight junction proteins ZO-1 and Occludin. Functional network analysis indicated that SEA and HCY regulate intestinal immune responses by promoting M1 macrophage polarization and the upregulation of pro-inflammatory cytokines, while simultaneously inhibiting anti-inflammatory factors. This study underscores the multifaceted adverse effects of SEA and HCY on male reproductive health and gut integrity, and highlights the need for further research into mechanisms and potential interventions to mitigate these harmful outcomes.