IntroductionHeating tobacco products (HTPs) are advanced electronic cigarette models. Classified by the FDA as a modified-risk tobacco product and can be used as part of efforts to quit smoking. Using heat-not-burn (HnB) technology, these devices heat tobacco avoiding complete combustion. Although the levels of toxicants in the mainstream are significantly lower than those observed in tobacco smoke, some recent studies have raised concerns about potential health risks associated with their use, particularly regarding their effects on male gonadal function, which remain largely unexplored.MethodsAdult male Sprague-Dawley rats were exposed, whole body, 5 days/week for 4 weeks to HnB mainstream.ResultsThe expression of the cell cycle regulators Bax/Bcl-2 ratio is not affected, along with no changes in p-38. On the other hand, an increase in oxidative stress markers, including those associated with DNA damage, was observed in exposed animals, along with the induction of NF-kB dependent pro-inflammatory mediators: TNF-α, IL-1β, IL-6 and COX-2. Furthermore, inactivation of key androgenic enzymes, such as 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase, together with decreased testosterone synthesis suggest a potential impairment of male gonadal function.DiscussionThe results indicate that animals exposed to HnB smoke show higher levels of oxidative stress markers, including those associated with DNA damage, as well as higher levels of pro-inflammatory cytokines. The impairment of some androgenic key enzymes and those related to the activity of seminiferous epithelium, together with the decrease in testosterone levels, suggest an impairment of gonadal function through the alteration of some cellular pathways typically associated with tobacco consumption.