Objectives To determine the prevalence of Peyronie's disease, a localized connective tissue disorder of the penile tunica albuginea, the symptoms of which include palpable plaque, painful erections and curvature of the penis, in a large sample of men in Germany. Subjects and methods A standardized questionnaire was sent to 8000 male inhabitants (age range 30±80 years) of the greater Cologne area (< 1.5 million inhabitants). Three questions about the selfdiagnosis of Peyronie's disease were previously assessed for validity on 158 healthy men and 24 patients with con®rmed Peyronie's disease. To optimize the response rate, the questionnaire was mailed three times to all the men. Results The response rate after the third mailing was 55.4% (4432 men); 142 men (3.2%, mean age 57.4 years, SD 13.4) reported the new appearance of a palpable plaque which, from the previous validation, was the most sensitive question and the main symptom of the disease. In men aged 30±39 years only 1.5% reported localized penile induration, compared with 3.0% in those 40±49 and 50±59 years, 4.0% in those 60±69 years and 6.5% of those >70 years old. Newly occurring angulation was reported by 119 of the 142 men (84%) and painful erection by 66 (46.5%). The combination of the three symptoms (plaque, deviation and painful erection) was reported by 46 of the 4432 respondents (1.04%), i.e. 32% of the 142 men with penile induration; 58 of the 142 men (41%) reported erectile dysfunction. Conclusions This is the ®rst large cross-sectional, community-based study to examine the prevalence of Peyronie's disease. Using previously validated questions the prevalence of Peyronie's disease in the sample was 3.2%; this is much higher than indicated in previous reports. A comparably high prevalence is reported for diabetes and urolithiasis, suggesting that this`rare' disease is more widespread than previously thought.
The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that peroxisome proliferator-activated receptor-gamma is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.
Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis.
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