Disturbed spermatogenesis associated with thickened lamina propria of seminiferous tubules is not caused by dedifferentiation of myofibroblasts

Abstract

BACKGROUND: 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. Methods The LP of testicular tissue from infertile men (n = 35) was investigated by new histological and morphometric approaches, RTPCR after laser microdissection and western blotting. Results 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. CONCLUSIONS 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. © The Author 2011. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.