Rolle von testikulären Mastzellen und ihrer sekretorischen Produkte bei der normalen und gestörten Hodenfunktion
Final Report Abstract
We believe that we have made substantial progress in our attempt to elucidate the ill-explored roles of mast cells in the human testis in health and disease, focusing on mast cell-peritubular cell interactions. The established cellular models for the human peritubular wall compartment, namely HTPCs, are a unique novel model for the study of normal peritubular cells, while HTPC-Fs open novel ways to study peritubular cells from infertility patients. In either situation the study of these cells bears a wealth of novel insights to the human testis. Thus we have for the first time identified molecular details of the nature of human peritubular cells: We found a number of secretory factors, reported contractile abilities and plasticity and interaction with mast cells via the secreted mast cell factors, TNFalpha and tryptase. In brief, human peritubular cells have the ability to secrete a number of important paracrine factors (e.g. GDNF, NGF, MCP-1, IL-6, decorin). Mast cells, which are present normally in low numbers in human testis, but are increased dramatically in numbers in cases of infertility, can regulate secretion of some, but not all of these factors. The enzymatic activity of the major mast cell product tryptase may furthermore cleave some of these products (e.g. proNGF/NGF), thus creating a complex microenvironment, which must be taken into consideration, not only with respect to the situation in the human testis, but in other human tissues, as well, in which NGF-producing cells and mast cells are found. The emerging results allow appreciating either cell type, i.e. peritubular cells and testicular mast cells, as important players in the normal and impaired human testis. The identification of decorin as a further mast cell stimulated secretory product of these cells and as a completely unknown factor in the human testis is also of interest. We found that it interferes with paracrine growth factor signaling. This may be of importance for the understanding of the patho-mechanisms involved in male infertility. Finally, human peritubular cells are contractile cells and HTPC/-Fs in culture retain this ability and open new avenues to study this property. Insights into the loss of contractility, which is associated with impaired spermatogenesis in men, have been obtained and we made progress in understanding, how contractility is being regulated. We believe that the results obtained and briefly summarized here, due to their focus on human are of great relevance to the understanding of human testis in health and disease, i.e. the clinical situation of male infertility, which affects a sizable proportion of men.
