RT Journal Article
T1 Vitamin D deficiency induces erectile dysfunction: Role ofsuperoxide and Slpi
A1 Bianca Barreira, 
A1 Francisco Perez-Vizcaino, 
A1 Olivencia Plaza, Miguel Ángel
A1 Climent Flórez, Belén
A1 Morales Cano, Daniel
A1 Moreno Gutiérrez, Laura
A1 Rodríguez Prados, Claudia
A1 Prieto Ocejo, Dolores
A1 Cogolludo Torralba, Ángel Luis
A1 Pérez Vizcaíno, Francisco
AB 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.
PB Willey
YR 2025
FD 2025-08-01
LK https://hdl.handle.net/20.500.14352/130083
UL https://hdl.handle.net/20.500.14352/130083
LA eng
NO Olivencia MA, Climent B, Barreira B, Morales-Cano D, Sánchez A, Fernández A, García-Gómez B, Romero-Otero J, Rodríguez C, Moreno L, Prieto D, Larriba MJ, Cogolludo A, Angulo J, Perez-Vizcaino F. Vitamin D deficiency induces erectile dysfunction: Role of superoxide and Slpi. Br J Pharmacol. 2025 Aug;182(15):3669-3687. doi: 10.1111/bph.70034. Epub 2025 Apr 13. PMID: 40222751.
DS Docta Complutense
RD 14 ene 2026