Fumonisin-Induced Disruptions in Sphingolipid Metabolism: Implications for Steroid Hormone Biosynthesis and Hormone...

Fumonisins, a class of mycotoxins produced primarily by Fusarium fungi, pose significant health risks to humans and animals through contamination of the food and feed chains. They rank among the most prevalent mycotoxins contaminating maize and maize-derived feeds worldwide, resulting in chronic dietary exposure of both humans and livestock populations across many regions. Their core mechanism of action is the inhibition of ceramide synthases (CerS), which disrupts the essential balance of sphingolipid metabolism by causing an accumulation of free sphingoid bases and a depletion of complex sphingolipids. Both sphingolipids and steroidogenesis are metabolically linked to mitochondrial, membrane and kinase-cascade mechanisms; hence this metabolic disruption may consequently affect steroid hormone biosynthesis, triggering toxicity phenotypes marked by impaired gametogenesis hormonal imbalances, and compromised pregnancy outcomes across mammalian species. Despite the established link between fumonisins and sphingolipid disruption, there is a gap in the literature, as no study to date has integrated sphingolipid disruptions with steroid hormone levels in a dose-dependent manner within reproductive tissues in vivo. This review synthesizes current scientific knowledge across mammalian species to highlight the risks fumonisins pose to reproductive physiology and to identify directions for future research.