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Updated: Aug 10, 2025
Intracavernous Pressure Recording in a Cavernous Nerve Injury Rat Model
Published on: September 20, 2021
Pathway analysis of microarray data from corpora cavernosal tissue of patients with a prostatectomy or Peyronie
Tim Searl1, Samuel Ohlander1, Kevin T McVary2
1Department of Urology, University of Illinois at Chicago, Chicago, IL 60612, United States.
Introduction:
Patients with a prostatectomy are at high risk of developing erectile dysfunction (ED) that is refractory to phosphodiesterase type 5 inhibitors. The cavernous nerve (CN) is frequently damaged during prostatectomy, causing loss of innervation to the penis. This initiates corpora cavernosal remodeling (apoptosis and fibrosis) and results in ED.
Aim:
To aid in the development of novel ED therapies, the current aim was to obtain a global understanding of how signaling mechanisms alter in the corpora cavernosa with loss of CN innervation that results in ED.
Methods:
Microarray and pathway analysis were performed on the corpora cavernosal tissue of patients with a prostatectomy (n = 3) or Peyronie disease (control, n = 3). Results were compared with an analysis of a Sprague-Dawley rat CN injury model (n = 10). RNA was extracted by TRIzol, DNase treated, and purified by a Qiagen Mini Kit. Microarray was performed with the Human Gene 2.0 ST Array and the RU34 rat array. Differentially expressed genes were identified through several analytic tools (ShinyGO, Ingenuity, WebGestalt) and databases (GO, Reactome). A 2-fold change was used as the threshold for differential expression.
Outcomes:
Pathways that were altered (up- or downregulated) in response to CN injury in the prostatectomy patients and a rat CN injury model were determined.
Results:
Microarray identified 197 differentially expressed protein-coding genes in the corpora cavernosa from the prostatectomy cohort, with 100 genes upregulated and 97 genes downregulated. Altered signaling pathways that were identified that affect tissue morphology included the following: neurologic disease, cell death and survival, tissue and cellular development, skeletal and muscle development and disorders, connective tissue development and function, tissue morphology, embryonic development, growth and proliferation, cell-to-cell signaling, and cell function and maintenance. These human pathways have high similarity to those observed in the CN-injured rat ED model.
Clinical Implications:
Significant penile remodeling continues in patients long after the acute surgical injury to the CN takes place, offering the opportunity for clinical intervention to reverse penile remodeling and improve erectile function.
Strengths And Limitations:
Understanding how signaling pathways change in response to CN injury and how these changes translate to altered morphology of the corpora cavernosa and ensuing ED is critical to identify strategic targets for therapy development.
Conclusion:
Altered signaling in pathways that regulate tissue homeostasis, morphogenesis, and development was identified in penes of patients with a prostatectomy, and competitive forces of apoptosis and proliferation/regeneration were found to compete to establish dominance after CN injury. How these pathways interact to regulate penis tissue homeostasis is a complex process that requires further investigation.
Insights
Prostatectomy can cause erectile dysfunction (ED) due to cavernous nerve (CN) damage. This study reveals altered signaling pathways in penile tissue, offering targets for new ED therapies.
Area of Science:
- Urology
- Molecular Biology
- Regenerative Medicine
Background:
- Prostatectomy frequently leads to erectile dysfunction (ED) resistant to standard treatments.
- Cavernous nerve (CN) damage during surgery causes penile tissue remodeling, including apoptosis and fibrosis, resulting in ED.
Purpose of the Study:
- To understand how signaling mechanisms in penile tissue change after CN injury.
- To identify potential therapeutic targets for treating post-prostatectomy ED.
Main Methods:
- Microarray and pathway analysis of penile tissue from prostatectomy patients and a rat CN injury model.
- Identification of differentially expressed genes and altered signaling pathways using bioinformatics tools.
Main Results:
- 197 protein-coding genes were differentially expressed in prostatectomy patients' penile tissue.
- Altered pathways involved in cell death, tissue development, and cell signaling were identified.
- These changes showed similarity to those in the rat CN injury model.
Conclusions:
- Signaling pathways regulating tissue homeostasis and development are altered post-CN injury.
- Apoptosis and proliferation pathways compete, driving penile remodeling and ED.
- Understanding these pathways is crucial for developing novel ED therapies.
