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Nitric oxide synthase in diabetic rat testicular tissue and the effects of pentoxifylline therapy
Mehmet Fatih Sönmez1, Eser Kılıç2, Derya Karabulut1
1a Department of Histology and Embryology , Faculty of Medicine, Erciyes University .
Abstract:
Diabetes is known to be associated with erectile dysfunction, retrograde ejaculation, level of testicular hormone, and a decrease in semen quality, respectively. In this project, we aimed to investigate at the molecular level, the effects of NOS on testes pathology in diabetes and examine the effects of pentoxifylline on healing. A total of 50 Wistar albino male rats were divided into five groups: Group I control; Group II only diabetes; Group III and IV diabetes + pentoxifylline; Group V only pentoxifylline. Group III rats received 50 mg/kg/day pentoxifylline during two months. In comparison, Group IV rats received saline in the first month followed by 50 mg/kg/day of pentoxifylline for the following month. NOS expression in testicular tissue was assessed using qRT-PCR, western blot, and immunohistochemistry. The mean seminiferous tubule diameter, Johnsen's testicular biopsy score, and serum testosterone levels decreased compared to controls. In contrast, the number of apoptotic cells, the levels of nNOS, iNOS and eNOS mRNA, and protein increased when compared to the control. Upon pentoxifylline therapy NOS decreased suggesting that it contributes to this damage and treatment with pentoxifylline may be effective in reversing this damage.
Insights
Diabetes negatively impacts male reproductive health, increasing nitric oxide synthase (NOS) in testes. Pentoxifylline treatment shows promise in reversing this diabetes-induced testicular damage.
Area of Science:
- Reproductive Endocrinology
- Molecular Biology
- Diabetology
Background:
- Diabetes mellitus is linked to male reproductive dysfunction, including hormonal imbalances and reduced semen quality.
- Nitric oxide synthases (NOS) play a role in testicular function, but their specific involvement in diabetes-associated pathology is not fully understood.
Purpose of the Study:
- To investigate the molecular effects of NOS on testicular pathology in diabetic rats.
- To evaluate the therapeutic potential of pentoxifylline in mitigating diabetes-induced testicular damage.
Main Methods:
- Utilized a rat model of diabetes, divided into control, diabetic, diabetic + pentoxifylline, and pentoxifylline-only groups.
- Assessed NOS expression (nNOS, iNOS, eNOS) at mRNA and protein levels using qRT-PCR, Western blot, and immunohistochemistry.
- Evaluated testicular histopathology, seminiferous tubule diameter, Johnsen's score, and serum testosterone levels.
Main Results:
- Diabetes led to decreased seminiferous tubule diameter, Johnsen's score, and testosterone levels.
- Diabetic rats exhibited increased apoptotic cells and elevated levels of nNOS, iNOS, and eNOS mRNA and protein.
- Pentoxifylline treatment reduced NOS levels, suggesting a reversal of diabetes-induced damage.
Conclusions:
- Diabetes induces testicular damage mediated by increased nitric oxide synthase expression.
- Pentoxifylline demonstrates potential therapeutic efficacy in reversing diabetes-associated testicular pathology.
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