(057) Influence of Circadian Disruption on Erectile Function in Chronic Jet-Lagged Young Rats

Abstract

Sleep is crucial during the developing stage of one’s life and has been associated with physical activity. However, as the number of 24-hour stores such as convenience stores and supermarkets have increased, along with increased internet usage, people have developed the habit of staying up late, resulting in sleep deprivation due to disruption in the light-dark cycle. Jet lag is widely used in animal models for inducing irregular circadian rhythms. Chronic jet lagged model animals are known to develop a variety of disorders. To investigate the influences of chronic jet lag on erectile function in rats in order to elucidate the effects of irregular circadian rhythms on future sexual function. 4-week-old rats underwent randomly assigned to remain either under the control light/dark cycle (Cont group) or under chronic light/dark shift schedule to simulate the conditions of chronic jet lag (CJL group). The shift-lag protocol consisted of 8 h light/dark phase advances repeated every 3 days for 4 weeks. Erectile function was examined at 1, 2, and 4 weeks post CJL treatment. After 4 weeks of CJL treatment, the rats were returned to control light/dark cycle for 4 and 8 weeks, as CJL(4w)+Rest(4w) group and CJL(4w)+Rest(8w) group, and erectile function was examined correspondingly. Erectile function was tested using intracavernous pharmacotherapy (ICP) measurements, and endothelial function was tested through an isometric tension study. Western blot analysis was used to assess the levels of endothelial nitric oxide (eNOS) and phosphorylated eNOS (p-eNOS). Additionally, mRNA expressions of clock genes (Bmal1 and Cry 1) and growth factors (TGF-β1 and ICAM-1) were tested using real-time PCR. The ICP/MAP ratio was significantly lower in the CJL group (0.35 ± 0.05) at 4 weeks than in the control group (0.66 ± 0.05) (P < 0.05). CJL group exhibited significantly lower testosterone levels, Bmal1, Cry 1, TGF-β1, and ICAM-1 expression, and p-eNOS and cGMP levels. The ICP/MAP ratio in the CJL(4w)+Rest(4w) group (0.47 ± 0.06) was lower than that in the control group (P < 0.01) whereas the ratio in the CJL(4w)+Rest(8w) group (0.81 ± 0.03) was similar to that in the control group (P > 0.05). In this study, chronic jet lagged (4 weeks) rats exhibited a decreased ICP/MAP ratio, reduced testosterone level, and decreased p-eNOS expression, indicating the development of erectile dysfunction (ED). Upon 8 weeks of normal light/dark shift schedule, erectile function was recovered. This study suggests that irregular circadian rhythms induced by repeated jet lag, especially in childhood, may affect the production of sex hormones and erectile function in the future. Therefore, it is necessary for children to follow a regular circadian rhythm and healthy lifestyle. No.