The aryl hydrocarbon receptor: a new frontier in male reproductive system

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically recognized for its role in the regulation of toxicity mediated by environmental chemicals. Recent research points to AhR’s critical participation in male reproductive physiology, particularly in spermatogenesis, hormone signaling, and the maintenance of sperm quality. Both endogenous ligands (e.g., dietary and gut microbiota-derived metabolites) and exogenous pollutants (e.g., dioxins and benzo-α-pyrene) influence AhR-mediated pathways, making it a key link between environmental exposures and male fertility. This review highlights AhR’s influence on the male reproductive system, emphasizing the role of endogenous AhR ligands and AhR expression in the maturation and function of male reproductive organs. Environmental AhR agonists have been shown to induce oxidative stress, hormonal imbalance, and sperm DNA damage, which impact harmfully on the spermatogenesis process, which leads to reproductive abnormalities. Conversely, certain natural compounds such as resveratrol, curcumin, and lycopene appear to antagonize AhR activation and reduce its negative effects, thus offering potential protective benefits against male reproductive toxicity. Nevertheless, discrepancies persist regarding the exact interplay between AhR signaling and critical reproductive hormones such as testosterone and LH, and it remains unclear how transgenerational epigenetic changes triggered by AhR activation might affect long-term male fertility. AhR is pivotal in male reproductive physiology, influencing spermatogenesis, sperm quality, and hormone regulation through its interactions with both endogenous and environmental ligands. Persistent pollutants such as dioxins and polycyclic aromatic hydrocarbons cause oxidative damage and hormonal disturbances via AhR, contributing to reduced sperm quality and fertility. The Impact of ligands of Aryl Hydrocarbon Receptor (AhR) on Male Reproductive Health. →, activation; $$\dashv$$ , inhibition; DEHP, Di(2-ethylhexyl) phthalate; I3C, indole-3-carbinol; PAH, polycyclic aromatic hydrocarbon; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin (Created by Biorender.com).