Exenatida e exendina(9-39) oriundos do lagarto venenoso Heloderma suspectum e seus efeitos sobre a qualidade espermática de ratos obesos e diabéticos

Abstract

The effects of exenatide (EXE) and exendin(9-39) (EXE9), peptides isolated from poisonous lizard H. suspectum on obesity and diabetes mellitus on male fertility are still poorly understood. The aim of this study was to evaluate the effects of EXE and EXE9 on parameters that contribute to sperm quality in hypothalamic injury-induced obesity (MSG) and hypercaloric diet (DIO) as well as streptozotocin-induced diabetes mellitus (STZ). Obese and diabetic rats received 10μg EXE / kg or 100μg EXE9 / kg sc daily or remained untreated for 20 days. Healthy rats at same age for each experimental models were used for comparison, only MSG model used healthy rats treated with exenatide. Biometric and glucoregulatory parameters treated with EXE (STZ) and EXE9 (STZ, DIO, MSG) were evaluated. Blood, testes and tail of the epididymis were collected. Sex hormones, leptin and insulin were evaluated by ELISA. Sperm were obtained from the epididymal tail by washing with HTF culture medium. The percentage of abnormal sperm morphology was analyzed under a phase contrast microscope. Functional analyzes of sperm were performed only STZ and MSG models. Sperm kinetics was evaluated by Computer Aided Analysis. The EXE-treated STZ group (STZ-E) improved the biometric parameters, glycemic control as well as the morphology, functionality and kinetics of mature sperm and EXE9 (STZ-E9) has an EXE effect on essential parameters for maintaining sperm quality. DIO showed impaired sperm quality, but there were occasional changes in the parameters that affect sperm quality. DIO-E improved sperm quality, suggesting that the antiobesogenic, antidislipidemic, and antidiabetogenic action of EXE restored the accuracy of the pathway of mature sperm, whereas treatment with EXE9 did not dramatically affect sperm kinetics, but was unable to restore path accuracy. EXE, through glucoregulatory improvement in MSG, has beneficial effects on hormone levels as well as sperm morphology, functionality and kinetics. Negative changes caused by EXE9 in glycorregulatory parameters, exacerbated increase in mass of periepididimal adipose tissue deposition, decreased testosterone and FSH plasma levels, with consequences on kinetics negatively affect sperm quality. EXE has been shown to be an excellent therapeutic agent to be used for beneficial effects on sperm quality in obese and diabetic patients. Results of treatment with EXE9 similar to those obtained with EXE in some evaluated parameters suggest two hypotheses (1) the use of an alternative to classical receptor; or (2) a dose-dependent situation if the dose of EXE9 administered is not sufficient for its action as an antagonist in a given organ and / or tissue. Therefore clinical research is needed to deepen the knowledge as well as the use of exenatide in a new incretinomimetic function as therapy.