Vitamin D3 is an important element in improving erectile function. However, the mechanisms of vitamin D3 remain unknown. Thus, we explored the effect of vitamin D3 on erectile function recovery after nerve injury in a rat model and investigated its possible molecular mechanisms. Eighteen male Sprague–Dawley rats were used in this study. The rats were randomly divided into three groups: the control, bilateral cavernous nerve crush (BCNC), and BCNC + vitamin D3 groups. BCNC model was established in rats by surgery. The intracavernosal pressure and the ratio of intracavernosal pressure to mean arterial pressure were utilized to evaluate erectile function. Masson trichrome staining, immunohistochemistry, terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling and western blot analysis were performed on penile tissues to elucidate the molecular mechanism. The results indicated that vitamin D3 alleviated hypoxia and suppressed the fibrosis signalling pathway by upregulating the expression of eNOS (p = 0.001), nNOS (p = 0.018) and α-SMA (p = 0.025) and downregulating the expression of HIF-1α (p = 0.048) and TGF-β1 (p = 0.034) in BCNC rats. Vitamin D3 promoted erectile function restoration by enhancing the autophagy process through decreases in the p-mTOR/mTOR ratio (p = 0.02) and p62 (p = 0.001) expression and increases in Beclin1 expression (p = 0.001) and the LC3B/LC3A ratio (p = 0.041). Vitamin D3 application improved erectile function rehabilitation by suppressing the apoptotic process through decreases in the expression of Bax (p = 0.002) and caspase-3 (p = 0.046) and an increase in the expression of Bcl2 (p = 0.004). Therefore, We concluded that vitamin D3 improved the erectile function recovery in BCNC rats by alleviating hypoxia and fibrosis, enhancing autophagy and inhibiting apoptosis in the corpus cavernosum.
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We thank the pathological laboratory of West China Hospital for their technical assistance with this research. This research was supported by the Natural Science Foundation of China (81871147 and 82071639) and the Chengdu Science and Technology Program (2019-YFYF-00087-SN).
The authors declare no competing interests.
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Zhu, S., Xiong, Y., Yu, B. et al. Vitamin D3 improved erectile function recovery by regulating autophagy and apoptosis in a rat model of cavernous nerve injury. Int J Impot Res (2023). https://doi.org/10.1038/s41443-023-00679-4