Corpus cavernosum smooth muscle cell dysfunction and phenotype transformation are related to erectile dysfunction in prostatitis rats with chronic prostatitis/chronic pelvic pain syndrome

Abstract

Background: The relationship between chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and erectile dysfunction (ED) has been shown in many studies. However, the specific mechanism remains unclear. This study was to investigate the corpus cavernosum smooth muscle cell function and phenotype transformation in Experimental autoimmune prostatitis (EAP) rats. Methods: EAP was induced in rats by using prostate protein supplemented with immuneadjuvant extraction, and the max-ICP and MAP were measured. IHC and Masson staining were done to assess inflammatory infiltration and collagen deposition in the corpus cavernosum, respectively. Subsequently, normal rat and EAP rat CCSMCs were purified by tissue block implantation and differential adherence method. The oxidative stress, smooth muscle phenotype transformation, cell cycle and intracellular calcium ion transport were also evaluated. Results: The ratio of max ICP/MAP in EAP rats significantly reduced, and the TNF-α content and collagen deposition in the corpus cavernosum markedly increased as compared to healthy rats. High-purity rat CCSMCs were obtained. Oxidative stress was evident and the cGMP content decreased in the EAP rat CCSMCs. The expression of Cav1.2, IP3R1 and RyR2 increased, but the SERCA2 expression decreased in EAP rat CCSMCs, which was accompanied by increased intracellular calcium. Increased expression of OPN, collagen and KCa3.1, decreased Calponin expression and increased proportion of cells in the S phase were also observed in the EAP rat CCSMCs. Conclusion: CP causes oxidative stress and imbalance of intracellular calcium in CCSMCs and promotes CCSMCs transformation from contractile to synthetic state, which may be involved in the pathogenesis of ED.

Chronic Prostatitis: Impact of Lifestyle, Infection, and Inflammation on Semen Parameters

“…Chronic prostatitis is a disease of young adults under 50 years [8], [40], [41] characterized by voiding symptoms, genitourinary pain, and often sexual dysfunction, that may lead to impaired sexual and reproductive health [7], [8], [42], [43], [44], such as erectile dysfunction and premature ejaculation [42], [45], [46], [47], [48]. Erectile dysfunction is 3.6 times more common in men with chronic prostatitis symptoms [49], and up to 35% of patients with chronic prostatitis experience erectile dysfunction [48]. Premature ejaculation is one of the most common sexual dysfunctions, affecting up to 30% of men, with severe consequences on life quality such, leading to stress, frustration, and even desire to avoid sexual intercourse.…”

“…Regarding to erectile function, an erection occurs when endothelial nitric oxide synthase and neuronal enzymes release, which increases the production of cyclic guanine monophosphate, favoring the relaxation of the arterial wall of the smooth muscle cells of the corpus cavernosum [49]. However, chronic prostatitis altered the relaxation of the arterial wall, and tadalafil has been proposed as a potential treatment [51].…”

Infiltration of inflammatory factors induced penile damage in chronic prostatitis

“…Clinical studies have found that about 29% of CP patients have ED and several clinical cohort studies have confirmed that CP is one of the clinical risk factors of ED (Fan et al., 2020). In recent years, some scholars had found that the phenotype of rat corpus cavernosum smooth muscle cells can transfer from contractile type to synthetic type in EAP rats (Wang et al., 2020). Simultaneously, the penile tissue of EAP rats had endothelial cell damage with a decrease in the expression of eNOS (Huang et al., 2019).…”

“…The expressions of calponin and α‐SMA were confirmed a decreasing trend in different EAP groups through WB results. Calponin was highly expressed in mature smooth muscle cells and increased with the maturation process (Hossain et al., 2003), but decreased when smooth muscle cells transformed from contractile type to synthetic type (Wang et al., 2020). As a microfilament of the actin family, α‐SMA contained the specificity that can regulate cell morphology and is mainly expressed in differentiated mature vascular smooth muscle cells, of which the expression changes can reflect the smooth muscle cell contractility (Han et al., 2020).…”

“…Long‐term chronic prostatitis has been proven to cause a series of adverse damage to the homeostasis and the models of experimental autoimmune prostatitis (EAP), as the classical models simulating human CP/CPPS, have been studied well (Du et al., 2020). There were evidences proved that inflammatory stress would induce the penile damage in EAP rats (Huang et al., 2019; Wang et al., 2020). Additionally, Huang et al.…”