Impact of diabetes on male sexual function in streptozotocin-induced diabetic rats: Protective role of soluble epoxide hydrolase inhibitor

Abstract

Diabetes-induced male sexual dysfunction is associated with endothelial dysfunction. Inhibition of soluble epoxide hydrolase (sEH) is known to improve endothelial function in diabetes. Therefore, we hypothesized that sEH inhibitor (sEHI), [trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid] / t-TUCB can restore the male sexual function in diabetic rat. After one week of administration of diabetogenic agent STZ (52 mg/kg i.p) injection, diabetic rats were treated with t-TUCB (0.1 and 0.3 mg/kg, p.o) or vehicle for 8 weeks. The sexual behaviour parameters of the animals were evaluated at the end of dosing period. The levels of testosterone and glucose in serum, and sperm were quantified. Effect of treatment on weight of reproductive organs and histopathology of penile tissue was evaluated. Diabetes had a negative effect on male sexual function, weight of sexual organs and production of sperm with a parallel decrease in the level of testosterone. The sEHI, t-TUCB, significantly preserved the sexual function and minimized an increase in the level of blood glucose in diabetic rats. It also prevented a decrease in the level of testosterone and sperm in diabetic rats, in comparison to diabetic control rats. Further, diabetes induced distortion of corpus cavernosum was attenuated by t-TUCB. Based on our findings, sEHI may delay the development of sexual dysfunction in diabetes.

Keywords: Corpus cavernosum; Diabetes-induced sexual dysfunction; Sperm count; Testosterone; sEH inhibitor t-TUCB.

Fig. 1.

The t-TUCB decreases diabetes-induced sexual dysfunction. An increase in the mount latency (A), intromission latency (B) and postejaculatory interval (C), but a decrease in the mount frequency (D), intromission latency (E) and ejaculatory latency (F) was observed in diabetic rats, in comparison to normal control rats. Diabetes-induced significant (^a p < 0.001) sexual dysfunction is evident due to increase in mount latency, intromission latency, post ejaculatory interval and decrease in mount frequency, intromission frequency and ejaculatory latency, in comparison to normal control animals. Treatment of t-TUCB significantly preserved sexual function, in comparison to diabetic control rats. * p < 0.05, ** p < 0.05, *** p < 0.001 when compared with diabetic control rats. NC: normal control, DC: diabetic control. Values are expressed as mean ± S.E.M. of six observations.

Fig. 2.

The t-TUCB minimizes an increase in the level of glucose in the serum of diabetic rats. Serum glucose level was significantly increased in the diabetic rats (^a p < 0.001) in comparison to the normal control rats. Treatment of t-TUCB prevented an increase in the serum glucose level (*** p < 0.001), in comparison to diabetic rats. NC: normal control, DC: diabetic control.

Fig. 3.

The t-TUCB improves sperm count and abnormal sperm of diabetic rats. Sperm count (A) was significantly decreased while % abnormal sperm (B) was significantly increased in the diabetic rats (^a p < 0.001), in comparison to the normal control rats. Treatment with t-TUCB minimized an increase in abnormal sperm and a decrease in sperm count in diabetic rats, in comparison to diabetic control rats. ** p < 0.05, *** p < 0.001 when compared with diabetic control rats. NC: normal control, DC: diabetic control. Values are expressed as mean ± S.E.M. of six observations.

Fig. 4.

The t-TUCB improves pathological changes of penile tissue in diabetic rat. Histopathology of penile tissue of normal rat (A) revealed a dilated corpus cavernosum lined with prominent endothelium, smooth muscle and fibroelastic connective tissue. Penile tissue of diabetic rat (B) revealed collapsed cavernous spaces and depleted endothelium. Penile tissue of diabetic rat treated with t-TUCB (0.1 mg/kg) (C) revealed few distortions of cavernous spaces lined by smooth muscle and connective tissue. Penile tissue of diabetic rat treated with t-TUCB 0.3 mg/kg (D) revealed cavernous spaces lined by endothelium with intact smooth muscle and fibroelastic connective tissue.