Investigation of the potential effects of chronic asprosin administration on the male reproductive system in adult male rats with induced sexual dysfunction

Asprosin, a glucogenic adipokine secreted by white adipose tissue cells, is a proteinaceous glucogenic adipokine that modulates hepatic glucose release by causing rapid release of glucose into the circulation during fasting. It is known that asprosine crosses the blood-brain barrier through a cAMP-dependent pathway and directly activates orexigenic AgRP and plays a role in sperm motility essential for fertilization through the olfactory receptor OLFR734. The fact that reproductive organs such as testes, like the brain, need free glucose at all times suggests that asprosin may also have an important role in reproductive functions. Based on this idea, we aimed to reveal the effects of asprosin on the hypothalamic-pituitary-gonadal axis and on reproductive functions in rats with paroxetine-induced sexual dysfunction. In our thesis study, 60 male Sprague Dawley rats were used as control, sham control, paroxetine, asprosine and paroxetine+asprosine groups (n=12). Paroxetine was administered via oral gavage, while asprosine infusion was administered via intracerebroventricular cannula. Following the behavioral experiments, rats were decapitated and body fluids and related tissues were collected for serum hormone levels, sperm parameters, histological examinations and gene expression analysis. SPSS 23 was used to evaluate the data and p values less than 0.05 were considered significant. As a result of our study, it was observed that asprosine infusion promoted erection in behavioral experiments and increased sexual motivation by facilitating ejaculation. In histologic examinations, paroxetine group rats showed edema and vascular congestion in the interstitial area and separation of the basement membranes of the seminiferous tubules, while paroxetine+asprosine group rats showed significant improvements (p<0.05). While there was no difference in epididymis weight between the groups, paroxetine treatment decreased sperm concentration compared to the control group (p<0.05) and asprosine increased sperm concentration and total motility compared to the control and paroxetine groups (p<0.01). In our investigations on serum hormone levels, asprosine decreased prolactin level (p<0.05) and increased oxytocin level (p<0.01). In our PCR studies, kisspeptin and RFRP3 expressions in the DMH region were found to be significantly increased in the asprosin-administered group compared to the control, sham control and paroxetine groups (p<0.05). Although kisspeptin levels were significantly lower in the paroxetine+asprosine group compared to the asprosine group, there was no significant difference compared to the other groups. In conclusion, this thesis is the first comprehensive study to investigate the potential effects of asprosin administration on reproductive physiology in male rats. The findings demonstrate that asprosin, acting through the OLFR734 receptor, exerts positive effects on male reproduction via olfactory pheromone pathways and may play a role in the central regulation of reproduction. The data obtained in this study provide strong evidence that asprosin and thus adipose tissue may have significant roles in the regulation of male reproductive physiology.