Telocytes of the male reproductive system: dynamic tissue organizers

Abstract

Telocytes are CD34⁺ interstitial cells that have long cytoplasmic projections (called telopodes), and have been detected in several organs, including those of the male reproductive system. In this brief review we evaluate the role of telocytes in tissue organization of the different organs of the male reproductive system in which these cells were studied. In general terms, telocytes act in the tissue organization through networks of telopodes that separate the epithelia from the stroma, as well as dividing the stroma into different compartments. In addition to this contribution to the structural integrity, there is direct and indirect evidence that such "walls" formed by telocytes also compartmentalize paracrine factors that they or other cells produce, which have a direct impact on morphogenesis and the maintenance of organ cell differentiation, as well as on their normal physiology. Moreover, alterations in telocytes and telopode networks are correlated with pathological conditions in the male reproductive system, in response to profound changes in structural organization of the organs, in inflammation, hyperplasia and cancer. Further studies are necessary to evaluate the molecular pathways telocytes employ in different contexts of physiology and disease.

Keywords: castration; paracrine factors; prostate cancer; smooth muscle; stromal compartmentalization; telopodes; testes; tissue organization.

FIGURE 1

Histological sections stained in HE and micrographs representing telocytes of different organs of the male reproductive system. (A, B) Histological sections stained in HE from the normal prostate of a species of rodent (Meriones unguiculatus) in which telocytes are present both at the periphery of the prostate epithelium and in the interalveolar stroma. (C, D) In the case of prostate with adenocarcinoma foci, telocytes are located only in regions where the epithelium is intact. In the vicinity of an adenocarcinomous region, telocytes are absent and the stroma is repopulated mainly by myofibroblasts, losing its typical configuration. (E) Telocytes can be seen in the periepithelial region and interalveolar stroma in a TEM image of the rodent prostate (Meriones unguiculatus). (F) Telocytes spread their telopodes in the interalveolar stroma in the vicinity of immune cells in a TEM image of rodent prostate (Meriones unguiculatus). (G, E) Telocytes are absent around a focus of hyperplasia in a TEM image of the rodent prostate (Meriones unguiculatus); at the same time, it is possible to see smooth muscle cells that have switched their phenotype to the synthetic profile and layers of smooth muscles that are dissociated. (I, J) Telocytes present at the periphery of the epithelium of seminiferous tubules of the testes in close association with the myoid cells and in the vicinity of the spermatogonia in a TEM image of a species of bat (Myotis nigricans). (K) Telocytes in the vicinity of the epididymal duct and surrounding the epithelium and smooth muscle cells in a TEM image of a species of bat (Platyrrhinus lineatus). Ep (Epithelium), St (Stroma), Arrows, Tc, blue (Telocytes), Pc (Prostate cancer), IC (Immune cell), Smc-c, green (Smooth muscle cells transitioning to the synthetic profile), H (Hyperplasia foci), Sp (Spermatogonia), Se (Sertoli cells), My (Myoid cells), White bar (1 µm), Blue bar (2 µm), Black bar (5 µm), Yellow bar (0.5 µm).

FIGURE 2

Schematic drawing depicting the telocytes of the prostate and testes. (A) Telocytes are present in the prostate both in the periepithelial region and in the interalveolar stroma. These cells form networks of thin processes (telopods) that connect them to each other and also to other cell types. In the prostate, telocytes are in close association with epithelial cells, muscle cells, nerve endings, blood vessels, immune cells and fibroblasts. (B) In the testes, telocytes are associated with the myoid cells that surround the seminiferous tubules; these cells also occupy the intertubular stroma and their telopode networks are linked to blood vessels, Leydig cells, fibroblasts, immune cells and nerve endings. Tc, yellow (Telocytes), Ep (Epithelium), Sm (Smooth muscle cell), Fb (Fibroblast), Ne (Nerve ending), My (Myoid cell), Se (Sertoli cell), Lc (Leydig cell), IC (Immune cells).