Quercetin-mediated restoration of high-fat diet-induced male reproductive dysfunction through modifying spermatogenesis and unraveling 3β-HSD, 17β-HSD, and StAR pathways.

PURPOSE: We explored the astounding potential of quercetin (QRT) to counteract the determinantal impacts of a high-fat diet (HFD) on testicular function in rat model. The goal was to understand how QRT, and its mechanisms of action can protect testicular health from HFD. METHODS: Rats were divided into four groups receiving a control diet, QRT supplement (100 mg/kg), HFD, or HFD plus QRT for 8 weeks. Afterward, assessments were conducted, and reproductive organs were analyzed for hormone levels, gene expression, and subjected to biochemical, histopathological, and immunohistochemical analyses. RESULTS: The HFD caused substantial declines in testicular weight, accessory sex glands and epididymis. The HFD also negatively impacted sperm characteristics including reduced motility, viability, and count, along with impaired morphology. Additionally, the HFD decreased testosterone levels in the testes and serum, impaired antioxidant enzymes like superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase, and reduced expression of key steroid metabolism enzymes 17β-hydroxysteroid dehydrogenase (17β-HSD), 3β-hydroxysteroid dehydrogenase (3β-HSD), and steroidogenic acute regulatory protein (StAR) involved in testosterone synthesis. These changes were paired with enhanced testicular lipid peroxidation, nitrite, and the inflammatory marker tumor necrosis factor-alpha (TNF-α), reflecting the damaging еffеcts of the HFD. Examination of testicular tissues verified structural damage and significantly fewer proliferating cell nuclear antigen (PCNA)-positive spermatogenic cells in seminiferous tubules of HFD-fed group, confirming HFD's adverse еffеcts. CONCLUSION: QRT supplementation was able to curb the harmful impacts of the HFD on testicular spermatogenesis and steroidogenesis through its antioxidant, anti-inflammatory and androgen boosting properties.