Aflatoxin B1-Induced male reproductive Toxicity: Bioactivation, mechanisms, molecular pathways, and Mitigation by phytochemicals in humans and animals

Abstract

Aflatoxins (AFTs) represent a major subclass of mycotoxins that are widely recognized as critical contaminants in both food systems and environmental matrices (soil, water, air dust). Among them, aflatoxin B1 (AFB1) is identified as the most toxic and biologically active compound, exhibiting a broad spectrum of deleterious effects, including nephrotoxicity, immunotoxicity, neurotoxicity, hepatotoxicity and genotoxicity. Increasing evidence has highlighted the role of AFB1 in impairing reproductive health, with a particular emphasis on AFB1-induced infertility in both humans and animals. The compound adversely affects the architecture and physiological functions of reproductive organs, leading to disrupted gametogenesis in males and consequent reductions in fertility rates. These testicular toxicities pose serious threats to public health, food security, and animal productivity. The molecular mechanisms implicated in AFB1-mediated reproductive damage include apoptosis, inflammation, autophagy, cell cycle dysregulation, and oxidative stress. Recently, naturally derived phytochemicals have emerged as promising countermeasures due to their low toxicity at appropriate doses and natural structural motifs. These bioactive compounds exert antioxidant, anti-inflammatory, and anti-apoptotic effects, thereby mitigating AFB1-induced germ cell toxicity. Additionally, certain phytochemicals modulate the biotransformation and detoxification of AFB1 in vivo, reducing its genotoxic potential and facilitating its excretion. This review provides a comprehensive analysis of AFB1-induced testicular toxicity in male mammals, with a focus on the underlying molecular pathways and protective roles of various plant-based agents. It further delineates the mechanistic basis for the anti-AFB1 activity of these phytochemicals, drawing attention to their shared properties and species-specific responses. Here, we identify existing gaps in current research and propose future directions to optimize phytochemical interventions. Overall, this review underscores the therapeutic potential of phytochemicals in alleviating AFB1-associated reproductive dysfunction through targeted modulation of critical signaling pathways.