Publications (3)8.71 Total impact
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ABSTRACT: Contractility of the peritubular smooth muscle layer ensures the transit of immotile spermatozoa through the epididymal duct to acquire their fertilizing capacity. Atrial natriuretic peptide (ANP) and nitric oxide (NO) affect contractility via cGMP signals that are controlled by phosphodiesterases (PDEs). Sildenafil inhibits the cGMP-hydrolyzing PDE5 and thereby promotes relaxation of smooth muscle cells. While sildenafil is increasingly used in young patients for the treatment of pulmonary hypertension, virtually no knowledge exists about PDEs in the epididymis. Western blotting, immunohistochemistry and RT-PCR analyses after laser capture microdissection localized PDE5 to smooth muscle cells, but not to epithelial cells, of the epididymal duct in man and rat. Sildenafil, ANP and NO significantly slowed spontaneous contractions of rat epididymal duct segments in organ bath studies. Sildenafil effects were additive to ANP and NO. Long-term exposure to sildenafil in vivo did not change the PDE5 expression or the observed contractility pattern with the rapid relaxing response toward ANP, NO and sildenafil. Data demonstrate that PDE5 is an important member of cGMP signaling pathways regulating the finely orchestrated process of epididymal duct contractility and suggest, however, that in the epididymis side effects of therapeutically used sildenafil are unlikely.Molecular and Cellular Endocrinology 02/2012; 349(2):145-53. · 4.04 Impact Factor
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ABSTRACT: In the human testis, myofibroblasts are the main cellular components of the lamina propria (LP) of seminiferous tubules. Thickened ('fibrotic') LP and dilated tubules are found in a large number of infertile patients, and myofibroblast dedifferentiation has been described in elderly men. It is not known, however, whether dedifferentiation of myofibroblasts is responsible for disturbed spermatogenesis associated with LP alterations. The LP of testicular tissue from infertile men (n = 35) was investigated by new histological and morphometric approaches, RT-PCR after laser microdissection and western blotting. Myofibroblasts were found in the LP of all seminiferous tubules. On the basis of LP morphology, each tubule could be assigned to one of the four groups, which showed increasing pathology: intact LP (Group 1), increased extracellular matrix (ECM) in-between the network of myofibroblasts (Group 2), two layers of myofibroblasts engulfing thickened ECM (Group 3) and LP additionally lacking an inner myofibroblast layer (Group 4). All myofibroblasts of all groups and of dilated tubules were fully differentiated, as could be shown by the expression of α-smooth muscle actin, myosin heavy chain, calponin 1 as well as relaxation-mediating cGMP-dependent protein kinase I and phosphodiesterase 5. Independently of the clinical background, the same patterns of thickened LP were detectable. There was a gradual decrease in intact spermatogenesis and in diameter/LP ratio from Groups 1 to 4, indicating that patterns of LP alterations reflect the quality of spermatogenesis. The thickness of myofibroblast layers increased towards Group 4 without cell proliferation, but CD34(+) cells, marking cells of haematopoetic lineage and progenitor cells (in lung fibrosis), were found in close proximity to tubules. Data indicate that dedifferentiation of myofibroblasts is not responsible for disturbed spermatogenesis associated with LP alterations. Thus, myofibroblasts, presumably newly developed in part, might contribute to disturbed spermatogenesis as key players during development of fibrotic LP alterations but not by contractile dysfunction.Human Reproduction 04/2011; 26(6):1450-61. · 4.67 Impact Factor
- BMC Pharmacology 01/2011; 11:1-2.