Aryl Hydrocarbon Receptor as a Target for Lycopene Preventing DEHP-Induced Spermatogenic Disorders

Di(2-ethylhexyl)phthalate (DEHP) is widely used as a plasticizer to improve product flexibility and workability. Lycopene (LYC) is a natural compound and has promising preventive potentials, especially antireproductive toxicity, but the specific underlying mechanism is yet to be fully defined. Our study investigated the effect of LYC on DEHP-induced spermatogenesis disorders. Male ICR mice were treated with DEHP (500 or 1000 mg/kg BW/day) and/or LYC (5 mg/kg BW/day) for 28 days. Our results indicated that LYC could relieve the DEHP-induced injury of seminiferous tubules and spermatogenic cells, swelling of endoplasmic reticulum (ER), and an increase of mitochondria. LYC prevented increased levels of nuclear damage to DNA and the deformity rate and decreased values of sperm motility, number, and density. Moreover, LYC treatment decreased DEHP-induced nuclear accumulation of aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT), and the expressions of their downstream target genes such as cytochrome P450-dependent monooxygenases (CYP) 1A1, 1A2, and 1B1 were markedly reduced to normal in the LYC treatment group. Our study showed that LYC can prevent DEHP-induced spermatogenic disorders via an AHR/ARNT signaling system. This study provided new evidence of AHR as a target for LYC, which can prevent DEHP-induced toxicity.