Genes involved in cell fate decisions during development also play key roles in continuous cell fate decisions made by adult organs. The Shh signaling pathway is critical for establishing the sinusoid morphology of the corpora cavernosa, and Shh continues to regulate and maintain penile morphology in the adult organ. In two rat models of ED, the BB/WoR diabetic rat and in the CN-injured Sprague Dawley rat, SHH protein is significantly decreased. In these same models there are significant morphological changes in the corpora cavernosa, including increased apoptosis and decreased smooth muscle and endothelial staining.
These changes are identical to those observed after SHH inhibition using a chemical inhibitor in normal rats. If decreased SHH protein is a cause of decreased smooth muscle and ED in diabetic and CN-injured penes, then examining the potential reversibility of SHH inhibition is of critical clinical significance. The experiments in this study provide evidence that the morphological changes caused by SHH inhibition are reversible in the rat with time, suggesting that the accompanying ED may also be reversible with reestablished/supplemented SHH signaling.