World J Mens Health.  2016 Dec;34(3):209-216. 10.5534/wjmh.2016.34.3.209.

Effects of Betulinic Acid on the Male Reproductive System of a Streptozotocin-Nicotinamide-Induced Diabetic Mouse Model

• Ahangarpour A
• Oroojan AA
• Khorsandi
• Arzani G
• Afshari G

• KMID: 2364204
• DOI: http://doi.org/10.5534/wjmh.2016.34.3.209

Abstract

PURPOSE
The present study was conducted to evaluate the favorable or harmful effects of betulinic acid (BA) on a diabetic reproductive system.
MATERIALS AND METHODS
In this experimental study, 60 male Naval Medical Research Institute mice (20∼25 g) were randomly divided into 6 groups: control, diabetes, diabetes+BA (10, 20, and 40 mg/kg), and diabetes+ metformin (200 mg/kg). A diabetic model was induced by a single dose of streptozotocin (STZ) (65 mg/kg) injection intraperitoneally 15 minutes after an intraperitoneal administration of nicotinamide (NA) (120 mg/kg). BA and metformin were gavaged for 2 weeks after confirmed diabetes induction in the treatment groups. One day after the last treatment, plasma luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone levels were evaluated. The cauda epididymis and testis were removed to analyze the sperm count and testis histopathology.
RESULTS
LH levels increased in diabetic (p<0.001) and diabetic BA-treated mice (p=0.009). Plasma levels of testosterone (p< 0.001) and sperm count (p=0.04) decreased in these groups when compared to the control group. Furthermore, administration of 10 mg/kg (p=0.001), 20 mg/kg (p=0.004), or 40 mg/kg (p<0.001) of BA led to a greater reduction in plasma testosterone levels compared to the diabetes group. Seminiferous tubule vacuole numbers increased in diabetic and diabetic BA-treated mice, but testis morphology and FSH level assessment revealed no significant differences between the groups.
CONCLUSIONS
STZ-NA can induce diabetic alterations in the male reproductive system and the administration of BA in diabetic treated mice resulted in a worse outcome.

Keyword

Betulinic acid; Diabetes mellitus; Mice; Spermatozoa; Testis

MeSH Terms

Academies and Institutes
Animals
Diabetes Mellitus
Epididymis
Follicle Stimulating Hormone
Humans
Luteinizing Hormone
Male*
Metformin
Mice*
Niacinamide
Plasma
Seminiferous Tubules
Sperm Count
Spermatozoa
Streptozocin
Testis
Testosterone
Vacuoles
Follicle Stimulating Hormone
Luteinizing Hormone
Metformin
Niacinamide
Streptozocin
Testosterone

Figure

• 

  Fig. 1 The effect of BA on plasma LH levels of normal and streptozotocin-nicotinamide-induced diabetic mice. Values are presented as mean±standard error, n=10. LH: luteinizing hormone, DM: diabetes mellitus, BA: betulinic acid (mg/kg), Met: metformin. *p<0.05 compared with the DM group, ##p<0.01, ###p<0.001 compared with the control group.

• 

  Fig. 2 The effect of BA on plasma FSH levels of normal and streptozotocin-nicotinamide-induced diabetic mice. Values are presented as mean±standard error, n=10. FSH: follicle stimulating hormone, DM: diabetes mellitus, BA: betulinic acid (mg/kg), Met: metformin.

• 

  Fig. 3 The effect of BA on serum testosterone levels of normal and streptozotocin-nicotinamide-induced diabetic mice. Values are presented as mean±standard error, n=10. DM: diabetes mellitus, BA: betulinic acid (mg/kg), Met: metformin. **p<0.01, ***p<0.001 compared with the DM group, ###p<0.001 compared with the control group.

• 

  Fig. 4 Effect of BA on the sperm count of normal and streptozotocin-nicotinamide-induced diabetic mice. Values are presented as mean±standard error, n=10. DM: diabetes mellitus, BA: betulinic acid (mg/kg), Met: metformin. #p<0.05 compared with the control group.

• 

  Fig. 5 The effect of betulinic acid (BA) on testis histopathology (H&E, ×400). (A) Control. (B) Diabetes. (C) Diabetes+10 mg/kg of BA. (D) Diabetes+20 mg/kg of BA. (E) Diabetes+40 mg/kg of BA. (F) Diabetes+metformin. V: vacuolation.

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