Obesity and sperm quality: Ghrelin as a possible therapeutic tool, alone or in synergy with physical exercise

Abstract

Obesity (Ob) is a pathology with high prevalence worldwide. Among other manifestations, it affects sperm quality in both animals and humans. In a previous study, we demonstrated that ghrelin (Ghrl) restores sperm quality affected by metabolic syndrome in rats. Physical exercise (Exc) is also an effective therapeutic tool, and there is a poorly characterized association between Exc and Ghrl secretion.

Working with a murine model, our hypothesis was that Ghrl reverses the negative effects of obesity on sperm quality and, in combination with Exc, exerts synergistic effects. To this end, by applying an obesogenic diet (ObD = 30% pork fat balanced food plus 5% fructose water) from weaning (day 21), we aimed to study the evolution of body weight and, in adulthood, the metabolic profile and sperm quality in male Wistar rats. We also evaluated whether the application of Exc (forced walking, 15 min, 3 times/week from day 65 to 103) and/or Ghrl (6 nmol/animal/day s.c. from day 85 to 103) would modify these results. Five groups were studied (n=11 animals/group): a) control diet (CD): balanced food + water, b) ObD, c) ObD + Ghrl, d) ObD + Exc, and e) ObD + Ghrl + Exc. Results were evaluated using ANOVA.

Ghrelin reversed the damage caused by obesity on sperm quality (P<0.05, sperm concentration: ObD = 18.8 ± 0.7 x10⁶/ml vs CD = 25.3 ± 0.7 x10⁶/ml, ObD + Ghrl = 26.4 ± 2.7 x10⁶/ml, ObD + Exc = 24.5 ± 2.2 x10⁶/ml, and ObD + Ghrl + Exc = 24.5 ± 1.9 x10⁶/ml; sperm motility ObD = 44.2 ± 3.4% vs CD = 57.9 ± 3.1%, ObD + Ghrl = 58.1 ± 3.2%, ObD + Exc = 53.3 ± 3.6%, and ObD + Ghrl + Exc = 59.2 ± 3.8%). It also slowed body weight gain and modestly improved dyslipidemia by significantly reducing plasma triglycerides and the triglycerides/LDL ratio. In all evaluated parameters, both metabolic and reproductive, the beneficial effects of Exc were confirmed. Ghrelin and Exc did not show synergistic effects.

In conclusion, both Ghrl and Exc were capable of reversing the negative effects of obesity on sperm quality; however, they did not show a synergistic effect. Since Ghrl has been used clinically for the treatment of chronic autoimmune diseases, and since Exc is not always an easily applicable option for obese patients, it may be feasible to evaluate the use of this hormone for the treatment of infertile obese men.