P-043 Vitamin D treatment reduces the mice testis damage generated by High-fat and vitamin D-deficiency diet via ameliorating oxidative stress

Abstract Study question Does vitamin D supplementation mitigate testicular dysfunction caused by a high-fat and vitamin D-deficient diet via modulation of PPARGC1A in an ICR mice model? Summary answer Vitamin D treatment significantly reduces oxidative stress, restores steroidogenic enzyme activity, and upregulates PPARGC1A, suggesting its role in protecting against diet-induced testicular damage. What is known already Oxidative stress is a key contributor to male infertility, often exacerbated by high-fat diets and vitamin D deficiency. PPARGC1A (PGC-1α) is a critical regulator of mitochondrial function and antioxidant defense, yet its role in testicular oxidative stress remains poorly understood. Vitamin D has been implicated in reproductive health due to its antioxidative and anti-inflammatory properties. However, evidence on whether vitamin D modulates PPARGC1A expression to mitigate testicular damage is limited. This study investigates the involvement of PPARGC1A in vitamin D-mediated protection against oxidative stress and steroidogenic dysfunction in an ICR mice model. Study design, size, duration This study utilized an ICR mice model (n = 24) to assess the effects of vitamin D supplementation on male reproductive health generated by obesity and/or vitamin deficiency testicular. Mice were divided into four groups based on diet: NC-VD, NC+VD, OB-VD and OB+VD groups. The study lasted for 2 years. Data in this study were analyzed statistically using one-way/ two-way ANOVA followed by Dunnett’s test orTukey’s test. Participants/materials, setting, methods This study utilized an ICR mice model (n = 24) to assess the effects of vitamin D supplementation on male reproductive health generated by obesity and/or vitamin deficiency testicular. Following the diet intervention, assessments were conducted on testicular tissue structure, sperm parameters and serum hormone levels. Oxidative stress in testicular tissue were evaluated. RNA sequencing and molecular docking analyses were utilized to identify differentially expressed genes and explore the molecular mechanisms underlying the observed effects Main results and the role of chance Mice in the OB-VD group exhibited significant testicular atrophy, reduced sperm count (p < 0.0001) and motility (p < 0.01), and increased oxidative stress markers. Vitamin D supplementation significantly restored sperm count (p < 0.05) and motility (p < 0.05), improved testicular morphology. Steroidogenic enzyme activity, including 3β-HSD and 17β-HSD, was markedly reduced in the OB-VD group (p < 0.0001, p < 0.01) but significantly upregulated following vitamin D treatment (p < 0.05, p < 0.01). Testosterone levels were significantly increased in the vitamin D-treated group (p < 0.0001).Oxidative stress markers, including ROS and malondialdehyde (MDA), were elevated in the OB-VD group (p < 0.01) and significantly reduced with vitamin D treatment (p < 0.05). Antioxidant enzyme superoxide dismutase (SOD) activity increased by 26% in the vitamin D-treated group (p < 0.05). Transcriptomic analysis identified PPARGC1A as a key regulator, with its expression significantly upregulated following vitamin D supplementation. Molecular docking and dynamics simulations confirmed strong binding interactions between vitamin D and PPARGC1A, suggesting its role in mitigating oxidative stress-induced testicular dysfunction.These findings highlight the potential therapeutic role of vitamin D in alleviating diet-induced male infertility. Limitations, reasons for caution Although this study provides strong evidence for the protective effects of vitamin D via PPARGC1A, its findings are limited to an animal model. Further clinical studies are needed to validate the translational relevance of PPARGC1A modulation in human male infertility. Wider implications of the findings Vitamin D supplementation may serve as a potential therapeutic strategy to mitigate oxidative stress-induced male infertility by upregulating PPARGC1A. These findings highlight the need for further research on the interplay between vitamin D, mitochondrial biogenesis, and reproductive health in clinical settings. Trial registration number No