Date of Award
Spring 2026
Document Type
Open Access Dissertation
Department
Biomedical Science
First Advisor
R. Clinton Webb
Abstract
Erectile dysfunction (ED) is a physiological condition that is prevalent in males over the age of 40 and is defined as the persistent inability to achieve and/or maintain an erection sufficient for satisfactory performance. Affecting inter-personal relationships, self- esteem and even family planning for younger individuals, ED remains an appreciable condition that can occur from multiple underlying risk factors. Despite the availability of gold-standard treatments (namely phosphodiesterase 5 inhibitors), 35% of ED- experiencing men are unresponsive to treatment, suggesting that the etiology of their ED needs to be investigated to understand the factors behind disease development. Common co-morbidities of ED exhibit an elevation in reactive oxygen species (ROS). Lipid metabolism is particularly sensitive to ROS - shifting from canonical pathways to lipid peroxidation (LP), an inflammatory process and driver of cell death. An important product of LP is octanal, a volatile fatty aldehyde. Previous literature has shown that octanal binds to olfactory receptor 2 (Olfr2) and can elicit NLRP3 inflammasome activation in vascular macrophages, leading to endothelial damage and vascular impairment. We hypothesize that octanal will impair erectile function by inducing an inflammatory response and causing corpus cavernosum dysfunction. To evaluate this, we utilized functional reactivity studies in the corpus cavernosum and pudendal arteries of 13-18-week-old C57Bl/6J mice. In conjunction with myograph studies, we explored the mechanism of Olfr2 activation using in vitro and ex vivo studies through RT-qPCR and GPCR activity assays. To connect these results to a physiological parameter, we performed intracavernous cannulation to measure intracavernosal pressure after cavernous nerve stimulation. We have established that octanal can impair the vascular and cavernosal reactivity, as well as the neurogenic function within the cavernosal body of the penis. Additionally, at 1 hour we observed the upregulation of NLRP3 in cavernosal smooth muscle cells in response to octanal (10 M), the Olfr2 antagonist citral (10 M) or combination treatment with octanal citral. Corresponding upregulation of the pro-inflammatory cytokine, IL-18 was also observed. We also see an upregulation of Olfr2 expression in the corpus cavernosal endothelial cells, suggesting that citral may have a dual role in vascular and cavernous impairment – it may behave as a partial agonist of Olfr2 or have off-target effects influencing upregulation of pro-inflammatory mediators. Together, these results support novel findings that the LP product, octanal, impairs vascular and sexual function through the activation of its receptor, Olfr2. We have also found that its antagonist, citral, has dual effects in both the corpus and the vasculature. These findings are the first of their kind to indicate that there is a functional olfactory receptor in the corpus cavernosum that has the potential to interfere with physiological function. While the exact mechanism of action leading to the impairment remains unknown, our data support our hypothesis that physiologically relevant levels of octanal induces an inflammatory cascade in the corpus cavernosum.
Rights
© 2026, Stephanie Ann Wilczynski
Recommended Citation
Wilczynski, S. A.(2026). Elucidating the Role of Olfactory Receptor 2 (Olfr2) in Vascular And Sexual (Dys)function. (Doctoral dissertation). Retrieved from https://scholarcommons.sc.edu/etd/8810