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Creatine monohydrate modulates testicular morphology and SOD1/NFκB-p65 immunoexpression in streptozotocin-induced
Ludmila Thainá Chaves Freitas1, Hailton Pereira de Melo Júnior1, Emily Lima Oliveira1
1Department of Morphology, Federal University of Rio Grande Do Norte, Natal, RN, Brazil.
Abstract:
Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia that may impair testicular function, including spermatogenesis and steroidogenesis. Creatine, an endogenously synthesized nitrogenous compound and one of the main reservoirs in the testes, is widely used, particularly among men. However, evidence regarding its effects on male reproductive health, especially under DM, remains limited. This study evaluated the impact of creatine supplementation on testicular morphology in streptozotocin-induced diabetic rats. Forty-eight adult Wistar rats were randomly assigned to four groups (n = 12 each): C, control; CT, creatine; D, diabetes; and DT, diabetes + creatine. Creatine-enriched chow was administered in two phases: a loading phase (13%; 130 g/kg) for 5 days prior to DM induction, followed by a maintenance phase (2%; 20 g/kg) for 35 days. Biochemical, histomorphometric, histopathological, and immunohistochemical analyses were performed. Compared to controls, group D showed increased seminiferous tubule and epithelial proportions, epithelial height, tubular volume (TV), and tubulosomatic index (TSI), while intertubular proportions decreased. DT normalized most morphological parameters to C group levels, and attenuated the diabetes-induced increases in TV and TSI. In the intertubular compartment, group D showed increased Leydig cell and connective tissue proportions versus C, while DT exhibited larger lymphatic spaces (vs. D) and the greatest Leydig cell nuclear diameter among all groups. Histopathological degeneration was significant in both D and DT and remained higher than in control levels. Immunohistochemistry revealed reduced SOD1 and increased NFκB-p65 expression in DT compared to D. These findings indicate that creatine supplementation is associated with morphometric and histopathological changes in the testicular parenchyma of diabetic rats, along with alterations in oxidative stress and inflammatory markers. Further studies are required to determine the functional implications for male reproductive health.
Insights
Creatine supplementation in diabetic rats altered testicular morphology and oxidative stress markers. While it normalized some parameters, histopathological damage and inflammation persisted, requiring further research into male reproductive health implications.
Area of Science:
- Reproductive Biology
- Endocrinology
- Metabolic Disorders
Background:
- Diabetes mellitus (DM) impairs testicular function, affecting spermatogenesis and steroidogenesis.
- Creatine is a key testicular compound, but its role in male reproductive health under DM is unclear.
Purpose of the Study:
- To investigate the impact of creatine supplementation on testicular morphology in diabetic rats.
- To assess changes in oxidative stress and inflammation markers.
Main Methods:
- Streptozotocin-induced diabetic Wistar rats were supplemented with creatine.
- Histomorphometric, histopathological, and immunohistochemical analyses were performed.
Main Results:
- Creatine normalized some diabetes-induced testicular morphological changes but did not prevent histopathological damage.
- Creatine altered Leydig cell morphology and increased lymphatic spaces.
- Creatine supplementation modulated oxidative stress (SOD1) and inflammation (NFκB-p65) markers.
Conclusions:
- Creatine supplementation affects testicular parenchyma in diabetic rats, with mixed effects on morphology and inflammation.
- Further studies are needed to clarify the functional consequences for male reproductive health.
