Interaction Between Telocytes and Mast Cells in Genetically Determined Non-Obstructive Azoospermia with AZFc Deletion: An Ultrastructural Study

In idiopathic azoospermia caused by non-obstructive infertility with AZFc deletion, the testicle usually contains an increased number of mast cells (MCs)—which are responsible for collagen synthesis in the testes—as well as Leydig cell hyperplasia. However, the relationship between MCs and telocytes in this pathology remains unexplored. The aim of this study was to examine ultrastructural changes in the interstitial tissue microenvironment of the convoluted seminiferous tubules in the testis, using clinical specimens from men with genetically determined non-obstructive infertility with AZFc deletion. Histological, immunohistochemical, and electron microscopic (EM) studies were performed on surgical materials from 14 patients with AZFc deletion. The IHC study was performed using a panel of antibodies: tryptase, chymase, carboxypeptidase A3, and αSMA. The EM study was performed on ultrathin sections with a thickness of 100–120 nm. MCs were found to be in a functionally active state and characterized by a variety of secretory activities. For the first time, telocytes and their colocalization with MCs and Leydig cells were visualized. It is possibly the telocytes—interacting with MCs—that synchronize the functional activity of the entire MC population of the testis. The interaction of MCs with telocytes, as well as individual secretory granules associated with loci of tropocollagen and collagen microfibril accumulation, leads to the accumulation of collagen fibrils in the interstitium, as observed in idiopathic infertility with AZFc deletion. Even with a small number of MCs in the interstitium of the convoluted seminiferous tubules in the testis, the telocytes are able to synchronize MCs’ activation and secretory activity, supporting the development of a profibrotic phenotype of the tissue microenvironment. The obtained results advance our understanding of idiopathic infertility with AZFc deletion by delineating the ultrastructural landscape of the testicular interstitium and establishing telocytes as key regulators of cellular crosstalk. Telocytes use complex mechanisms for the spatial integration of MCs and fibroblasts in the profibrotic phenotype formation of the convoluted seminiferous tubule tissue microenvironment. Potentially, telocytes can directly be involved in synchronizing such processes by activating the biogenesis and secretion of collagen monomers by fibroblasts; the MC secretome directly affects the polymerization of collagen monomers and dimers into microfibrils in the extracellular matrix, stimulating excessive collagen fiber formation and the development of fibrotic changes.