AhR-CatSper2 Crosstalk Attenuates HFD-Induced Testicular Dysfunction

High-fat diet (HFD)-induced obesity is an important cause of male reproductive dysfunction.Aryl hydrocarbon receptor (AhR) and sperm-specific CatSper2 calcium channel are critical for reproductive function.However, information on the interaction between these two pathways under metabolic stress conditions and its impact on obesity-induced male infertility remains unexplored.This study aimed to investigate functional significance of AhR-CatSper2 crosstalk in attenuating HFD-induced testicular dysfunction.Forty adult male albino rats were randomly allocated into four equal groups: control group was fed standard chow, HFD group was fed diet rich in fat, HFD-RES was fed HFD plus resveratrol 100mg/kg, and HFD-AhR -group was fed HFD with CH223191 10mg/kg intra-peritoneally every 72h).The experimental period lasted for 8 weeks.Testicular expression of AhR and CatSper2 genes, sperm progressive motility, viability, acrosomal integrity, DNA fragmentation, serum testosterone levels, and testicular histopathology were assessed in experimental rats.Results revealed that HFD elevated AhR expression, and suppressed CatSper2 expression compared to controls (P<0.05).Resveratrol upregulated AhR, with improvements in sperm progressive motility, viability, acrosomal integrity and DNA integrity compared to HFD group.In contrast, AhR antagonist reduced CatSper2 expression and led to severe impairments across all parameters, including the highest rates of sperm DNA fragmentation, sperm with abnormal acrosomes, and the lowest testosterone levels.Histopathological examination confirmed extensive germ cell loss and Sertoli cell damage in the HFD-AhR -group, while resveratrol preserved testicular architecture close to normal.In conclusion, AhR signaling protects against metabolic stress-induced reproductive damage, while resveratrol offers partial therapeutic benefit.Conversely, AhR blockade appears detrimental for testicular function and sperm quality.Knowledge about this pathway may open new spectrums for managing obesity-related male infertility.