Uncovering the penile clock: expression of molecular clock proteins in human penile cavernous tissue

Abstract

Purpose: To evaluate the expression of core molecular clock genes/proteins in penile cavernous tissue from healthy male subjects and to determine whether their expression has circadian variation. Materials and Methods: Corpus cavernosum biopsy samples were obtained from 10 healthy males with penile deviation or fracture who underwent surgical intervention during the day and night. The daytime group (n=5) underwent corpus cavernosum tissue sampling during zeitgeber time (ZT) 8-12, while the nighttime group (n=5) underwent sampling during ZT 20-24. The expression and localization of BMAL1, CLOCK, PER1, PER2, PER3, CRY1, and CRY2 proteins were analyzed using immunohistochemistry and quantified using H-score analysis. RT-qPCR analysis was performed to assess the expression of core molecular clock genes in the corpus cavernosum tissue of 5 additional daytime patients. Results: The expression of core molecular clock proteins was detected in vascular endothelial cells (VECs) and smooth muscle cells (SMCs) in corpus cavernosum during daytime and nighttime. BMAL1 exhibited the most significant nuclear expression during daytime in both cell types, whereas its expression decreased significantly at night. In VECs, a significant decrease in the nuclear expression of CRY1 was observed at night. In SMCs, a significant decrease in the cytoplasmic expression of PER3 was observed at night. The expression patterns of the core molecular clock genes were ascertained through a RT-qPCR analysis. Conclusions: Our research provides compelling evidence that core molecular clock genes are distinctly expressed in penile tissue in humans. Furthermore, we observed the expression of molecular clock proteins within the VECs and SMCs of the corpus cavernosum, with BMAL1 being the most prominently expressed. The discovery of core molecular clock genes in penile tissue, as well as proteins within the SMCs and VECs of the corpus cavernosum, introduces the potential significance of the molecular clock mechanism in the physiology of penile erection.