Novel control for erectile dysfunction research.

Abstract

Background: Erectile dysfunction (ED) is a serious medical condition that impacts quality of life. An underlying cause is loss of cavernous nerve (CN) innervation, which initiates remodeling of the corpora cavernosa of the penis, including smooth muscle apoptosis and increased collagen. There are few studies of penile remodeling in patients because of difficulty acquiring patient corpora cavernosa tissue, and appropriate controls; however, it is critical to ensure that our animal models adequately parallel patient conditions.

Aim: Penile morphology was examined in corpora cavernosa of reconstruction and Lapeyronie's patients, to determine if reconstruction corpora cavernosa may be useful as controls for morphological analysis.

Methods: Penis tissue was obtained from penectomy surgery within the context of genital reconstruction (n = 25) and corpora cavernosa tissue from Lapeyronie's (control, n = 10) patients undergoing prosthesis implantation surgery. Primary cell cultures were established from corpora cavernosa tissue and growth in response to Sonic hedgehog (SHH) treatment and inhibition, BMP4, and GREM1, were quantified. The effect of 17 β-estradiol on smooth muscle cultures was examined.

Outcomes: Collagen was quantified by hydroxyproline assay and smooth muscle by western (α-actin/GAPDH) of corpora cavernosa tissue. Immunohistochemical (IHC) analysis for α-ACTIN, CD31, P4HB, and nNOS and trichrome stain were performed to characterize the reconstruction tissue in comparison to Lapeyronie's controls.

Results: No differences in collagen and smooth muscle abundance were observed in the corpora cavernosa of reconstruction and Lapeyronie's patients. IHC showed normal smooth muscle, endothelium, fibroblasts, neurons, collagen, and SHH signaling in corpora cavernosa from reconstruction patients in comparison to Lapeyronie's controls. 17 β-estradiol treatment did not alter smooth muscle cell growth or the response to SHH pathway signaling.

Clinical translation: Most reconstruction patients undergo 17 β-estradiol treatment prior to surgery. While studies document the effect of estrogen on penile embryogenesis and hypospadias, little is known about estrogen impact on adult corpora cavernosa tissue. No difference in penile morphology, smooth muscle, and collagen abundance was observed in reconstruction patients who underwent 17 β-estradiol and anti-androgen treatment prior to surgery, suggesting that corpora cavernosa from these patients might be useful as controls for studies of ED.

Strengths and limitations: While no difference in corpora cavernosa morphology was observed, genomic and erectile function analyses were not performed.

Conclusions: No difference in penile morphology was observed in the corpora cavernosa of Lapeyronie's and reconstruction patients, suggesting that the corpora cavernosa of reconstruction patients may be useful as controls for morphological analysis, similar to Lapeyronie's tissue.

Statement of significance: In this study, we examine the morphology of corpora cavernosa tissue from reconstruction patients in comparison to Lapeyronie's controls, to understand how estradiol treatment alters adult penile architecture.