%0 Journal Article
%A Bianca Barreira
%A Francisco Perez-Vizcaino
%A Olivencia Plaza, Miguel Ángel
%A Climent Flórez, Belén
%A Morales Cano, Daniel
%A Moreno Gutiérrez, Laura
%A Rodríguez Prados, Claudia
%A Prieto Ocejo, Dolores
%A Cogolludo Torralba, Ángel Luis
%A Pérez Vizcaíno, Francisco
%T Vitamin D deficiency induces erectile dysfunction: Role ofsuperoxide and Slpi
%D 2025
%U https://hdl.handle.net/20.500.14352/130083
%X Background and purpose: Epidemiological studies suggest a relationship between vitamin D deficiency and erectile dysfunction (ED). We hypothesized that vitamin D deficiency or vitamin D receptor (VDR) knockout causes ED and analysed the underlying molecular mechanisms.Experimental approach: Erectile function was assessed in vivo in anaesthetized male mice or rats by evaluating intracavernosal pressure (ICP) and in vitro in male Vdr-/- mice, and rat or human isolated corpora cavernosa (CCs) mounted in a myograph. Bulk RNA-sequencing (RNA-seq) transcriptomic analysis was performed in rat CCs. Vitamin D deficiency was induced in rats fed a vitamin D-free diet for 5 months.Key results: CCs from human donors with low plasma vitamin D exhibited reduced nitric oxide (NO)-dependent erectile function. This ED was also reproduced in vitamin D-deficient rats and VDR knockout mice, in vivo and ex vivo, and is associated with penile fibrosis and reduced response to the phosphodiesterase 5 inhibitor (PDE5i) sildenafil. CCs from deficient rats show increased superoxide levels, and their impaired erectile function was restored by superoxide scavengers. Transcriptomic analysis, real-time polymerase chain reaction (RT-PCR) and Western blot showed down-regulated secretory leukocyte protease inhibitor (Slpi). Moreover, recombinant SLPI prevented superoxide-induced ED, while Slpi gene silencing led to reduced erectile function in a superoxide-dependent manner.Conclusion and implications: Vitamin D deficiency or VDR knockout reduces erectile function. We suggest that this effect is mediated by increased superoxide levels and down-regulation of SLPI. Vitamin D deficiency might be an aetiological factor for vascular ED and for the therapeutic failure of PDE5i.
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