Role of ROS/JAK2/STAT3 signaling pathway in di-n-butyl phthalate-induced testosterone synthesis inhibition and antagonism of lycopene

Di-n-butyl phthalate (DBP) causes adverse effects on male reproduction, especially testosterone synthesis inhi-bition. However, the specific mechanism of DBP-induced testosterone synthesis inhibition and its effective intervention measures of prevention and treatment are scarce presently. Lycopene (LYC) plays beneficial roles in male infertility because of its antioxidant activity. Nevertheless, it is unclear whether LYC could prevent DBP-induced male reproductive toxicity. By in vitro and in vivo investigations, this study demonstrated that DBP activated ROS/JAK2/STAT3 signaling pathway, promoted mitophagy and apoptosis, which in turn inhibited testosterone synthesis. Additionally, another major finding was that LYC supplement could reverse the above change, presenting as the restraint of ROS/JAK2/STAT3 signaling pathway, reduction of mitophagy and apoptosis, and improvement of testosterone synthesis. Our study facilitates deeper understandings of the mechanism in DBP-induced testosterone synthesis inhibition, and identifies LYC as the effective prevention and control strategies for DBP poisoning.

Automated summary

Di-n-butyl phthalate (DBP) is known to negatively affect male reproduction, particularly by inhibiting testosterone synthesis. However, the specific mechanism behind this inhibition and effective intervention measures are limited. This study found that DBP activates the ROS/JAK2/STAT3 signaling pathway, promotes mitophagy and apoptosis, leading to a decrease in testosterone synthesis. Furthermore, it was discovered that lycopene supplementation reverses these effects, inhibiting the ROS/JAK2/STAT3 signaling pathway, reducing mitophagy and apoptosis, and improving testosterone synthesis. This research enhances our understanding of the mechanism behind DBP-induced testosterone synthesis inhibition and identifies lycopene as an effective strategy for prevention and treatment of DBP poisoning.