Artificial Sweeteners and Male Infertility: Network Toxicology and Experimental Evidence Reveal Fgfr1 as the Critical Target

Scout Impact

This study investigates artificial sweeteners, specifically aspartame, neotame, and sucralose, and their impact on male fertility. The data demonstrates that these sweeteners bind to FGFR1, a critical gene associated with testicular function, leading to reproductive toxicity. Scout penalizes artificial sweeteners due to their confirmed negative effects on male reproductive health.

Key Findings

• Finding 1: Aspartame, neotame, and sucralose show high-confidence reproductive-toxicity signals.
• Finding 2: Ninety-one candidate targets were identified, with FGFR1 emerging as the core gene.
• Finding 3: Aspartame upregulated FGFR1, DUSP6, and SPRY2, and downregulated STAR in TM3 Leydig cells.
• Finding 4: Molecular docking and MD simulations confirmed stable binding of artificial sweeteners to FGFR1.
• Finding 5: Aspartame exposure levels ranged from 0.5-2mM over 48 hours in TM3 Leydig cells.

Limitations

• Limitation 1: The study was conducted in vitro using TM3 Leydig cells, which may not fully replicate in vivo conditions.
• Limitation 2: The findings are based on animal models, limiting direct generalizability to human populations.