Project Details
Projekt
The peritubular lamina propria testis and male Infertility: Relevance of contractility and fibrosis
Applicant
Professor Dr. Ralf Middendorff
Subject Area
Reproductive Medicine, Urology
Term
from 2008 to 2016
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 34016037
Peritubular contractile cells (myofibroblasts) of the lamina propria (LP), surrounding germ cells of seminiferous tubules, are crucial for the transport of immature sperm to the epididymis. Moreover, a thickened (fibrotic) LP coincides with disturbed spermatogenesis and infertility. Most recently, we showed that fully differentiated myofibroblasts are present in each tubule, even in case of thickened LP, indicating that disturbed spermatogenesis associated with thickened LP is not due to dedifferentiation of myofibroblasts. It is not known, however, whether contractility of whole tubules, with myofibroblasts surrounded by great amounts of extracellular matrix, is preserved. Using newly developed approaches to monitor tubular contractility in animal models {ex vivo and in vivo) and man (ex vivo), contractions of tubules with regular and thickened LP, luminal sperm transport and spermiatio will be analyzed and influenced pharmacologically. Thickening of LP resembles fibrotic changes observed in other organs. In lung and heart, deregulated epithelial-mesenchymal communication, fibroblast to myofibroblast transformation, migration of myofibroblasts, their provenance from non-fibroblastic progenitor cells and an involvement of cGMP pathways have been suggested. In the testis, however, mechanisms leading to LP fibrosis and the relevance of these alterations for disturbed spermatogenesis are unknown. Time course experiments with animal models, known to induce fibrosis, and to delete the germ cell population, respectively, will assess the role of myofibroblasts and help to clarify whether thickened LP results in disturbed spermatogenesis and/or whether thickened LP develops secondarily to disturbed spermatogenesis.
DFG Programme
Clinical Research Units
