Neurotrophic factors in the testis

Neurotrophic factors, interacting with neurons to affect their growth, are a subset of the polypeptide growth factors. There is increasing evidence for a broader physiological role of these factors which includes effects on a variety of nonneuronal tissues. Among the cell systems, where neurotrophic factors have been hypothesized to exert local nonneurotrophic activities, the testis is of particular interest. This organ represents a complex biological unit which requires the concerted action of very diverse cell types interacting with each other in order to ensure correct spermatogenesis. As signaling molecules that may be involved in these intercellular communication events, various neurotrophic factors have attained considerable scientific attention. This article intends to summarize the presently available data on the distribution and possible local activities of neurotrophic factors and their receptors in testicular cells and provides further information on local expression sites of some of these factors in the human testis.Biomedical Reviews 1999; 10: 25-30

Understanding spermatogenesis is a prerequisite for treatment

Throughout spermatogenesis multiplication, maturation and differentiation of germ cells results in the formation of the male gamete. The understanding of spermatogenesis needs detailed informations about the organization of the germinal epithelium, the structure and function of different types of germ cells, endocrine and paracrine cells and mechanisms, intratesticular and extratesticular regulation of spermatogenesis. Normal germ cells must be discriminated from malformed, apoptotic and degenerating germ cells and tumor cells. Identification of the border line between normal and disturbed spermatogenesis substantiate the diagnosis of impaired male fertility. The profound knowledge of the complicate process of spermatogenesis and all cells or cell systems involved with is the prerequisite to develop concepts for therapy of male infertility or to handle germ cells in the management of assisted reproduction

Dual nature of Leydig cells of the human testis

This review is devoted to the human Leydig cell, and systematizes published and own unpublished results from studies performed during the last decade. Leydig cells are the main cell type in the testis that produce androgens which are important for the development of the male genital organs, secondary sex characteristics and behavior as well as for the processing and maintenance of spermatogenesis. A lot of information accumulated provides evidence that Leydig cells of the human testis and the testis of some other species express or possess immunoreactivities for numerous marker substances characteristic for nerve and neuroendocrine cells. It is shown that human Leydig cells, beside of markers for steroidogenic activity, possess: neuronal markers, synaptic and storage vesicle proteins, neural cytoskeletal proteins, 5-hydroxytryptamine, enzymes involved in the synthesis of catecholamines, neurohormones and/or their receptors, neuropeptides, calcium-binding proteins, cell adhesion molecules, glial cell antigens, components of the nitric oxide/cyclic guanosine monophosphate system, components of the renin/angiotensin system, and numerous growth factors and their receptors. These results provide new evidence for the neuroendocrine nature of Leydig cells. As consequence, two main questions arise: (i) the origin of Leydig cells and (ii) their functional significance as neuroendocrine cells. The presumption that Leydig cells originate from mesenchymal-like cells of the mesonephros is the most common view in the literature. However, no data are provided concerning the origin of the stem cells from which the Leydig cell lineage develops. Mesenchyme comprises the embryonic connective tissue cells that may have mesodermal, ectodermal and neuroectodermal (neural crest) origin. In this relation and based on the recently established neuroendocrine feature, we speculate that Leydig stem cells may detach from unknown regions of the neural crest and migrate to the mesonephric and gonadal anlage at early stages of development. The functional significance of Leydig cells as neuroendocrine cells is also illustrated on the basis of the nitric oxide/cyclic guanosine monophosphate system. Accordingly, Leydig cells may regulate their steroidogenic activity by an intracrine or autocrine fashion. Furthermore, they are probably able to synchronize the activity of the cells in a Leydig cell cluster by a paracrine way. Leydig cells may influence the contractile activity of the smooth muscle cells of blood vessels, thus regulating the blood flow rate and the permeability for hormones and nutritive substances. Also, Leydig cells may regulate the contractile state of peritubular myofibroblasts and myofibroblasts and smooth muscle cells of the tunica albuginea. Similarly, Leydig cells may communicate with Sertoli cells and germ cells of the seminiferous tubules. Leydig cells are a relatively stable, heterogeneous population of cells in the human testis which persists even in cases of impaired spermatogenesis, fibrosis and different pathological changes of the testis. This fact suggests that Leydig cells survive under unusual conditions due to precise regulatory systems which make them to a larger extent independent from the local homeostasis.Biomedical Reviews 1996; 6: 11-41

Loss and recovery of androgen receptor protein expression in the adult rat testis following androgen withdrawal by ethane dimethanesulfonate.

Androgens are especially important for the maintenance of spermatogenesis in adulthood and the experimental withdrawal of testosterone (T) production by ethane dimenthanesulfonate (EDS) is a valuable tool for studying androgen-dependent events of spermatogenesis. The aim of the present study was to investigate the specific changes in immunoexpression of androgen receptor (AR) in the testis in relation to degeneration and regeneration of Leydig cell (LC) population and seminiferous epithelium. Immunohistochemistry for AR and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) as well as TUNEL assay for apoptosis were performed on testicular sections of control and EDS-treated rats. Serum LH and T levels were measured by RIA. Our results revealed a total loss of AR immunoexpression from the nuclei of Sertoli (SCs), LCs and peritubular cells during the first week after EDS administration and that coincided with severe drop in T levels. Two weeks after EDS administration, the AR expression was recovered in these cells but normal stage-specificity in SCs was replaced by uniform intensity of AR immunostaining at all the stages of the spermatogenic cycle. The stage-specific pattern of androgen expression in SCs with a maximum at stages VII-VIII appeared 5 weeks after treatment. LC immunoreactivity for 3beta-HSD at different time points after EDS administration correlated with values of T concentration. The maximal germ cell apoptosis on day 7 was followed by total loss of elongated spermatids 2 weeks after EDS treatment. Regeneration of seminiferous epithelium 3 weeks after EDS administration and onwards occurred in tandem with the development of new LC population indicated by the appearance of 3beta-HSD-positive cells and gradual increase in T production. The specific changes in AR after EDS including their loss and recovery in Sertoli cells paralleled with degenerative and regenerative events in Leydig and germ cell populations, confirming close functional relationship between Sertoli, Leydig and germ cells

Progenitor cells of the testosterone-producing Leydig cells revealed

The cells responsible for production of the male sex hormone testosterone, the Leydig cells of the testis, are post-mitotic cells with neuroendocrine characteristics. Their origin during ontogeny and regeneration processes is still a matter of debate. Here, we show that cells of testicular blood vessels, namely vascular smooth muscle cells and pericytes, are the progenitors of Leydig cells. Resembling stem cells of the nervous system, the Leydig cell progenitors are characterized by the expression of nestin. Using an in vivo model to induce and monitor the synchronized generation of a completely new Leydig cell population in adult rats, we demonstrate specific proliferation of vascular progenitors and their subsequent transdifferentiation into steroidogenic Leydig cells which, in addition, rapidly acquire neuronal and glial properties. These findings, shown to be representative also for ontogenetic Leydig cell formation and for the human testis, provide further evidence that cellular components of blood vessels can act as progenitor cells for organogenesis and repair

The pericyte progenitors and the pericytes are the ancestors of the inner ear structures

This short scientific overview concerns the morpho-functional comparison between the omnipresent pericytes and the pericytes of the inner ear and, besides some characteristic features of the last, provides evidence that the otic pericytes are authentic part of the omnipresent pericyte (adult stem cell) population of the vertebrate organism. In the present review we offer evidences for a new hypothesis that the pericyte progenitors and the pericytes, as pluripotent epiblast derivatives, are the ancestors of the supporting and hair cells of the Corti organ, the cells of the vestibular (balance) organ and the neural elements of the inner ear in norm and experiment. The most important evidences for this statement provide results concerning: 1. the origin of the inner ear vasculature; 2. the close relationships of the pericytes with the microvasculature of the inner ear (periendothelial location in microvascular niches); 3.their importance for the blood-labyrinth barrier; 4. the events that accompany the origin of the inner ear sensory epithelia; 5. the authentic stem cell qualities of the pericytes allowing the production of cells and tissues characteristic for the three embryonal germ layers: ectoderm, mesoderm and endoderm (during embryogenesis, in the adult organisms and at experimental and pathological conditions), as well as 6. the remarkable pericyte plasticity and their involvement in the immune system

The Leydig Cells of the Testis Originate from the Microvascular Pericytes

This review offers some clarifying thoughts about the nature and origin of the fetal and adult Leydig cells, supporting the conception that the pericytes (the periendothelial cells) and the smooth muscle cells of the microvasculature, that represent the main omnipresent adult stem cell population of the mammalian organism, are the Leydig cell ancestors. Our attention is specifically dedicated to the numerous contradictions as well as ambiguities concerning the hypotheses that the mesenchymal stromal cells (MSCs), the neural crest stem cells (NCSCs) and the peritubular myoid stem cells (PMCs) represent the stem ancestors of the Leydig cells. In effect, it becomes evident that the only pluripotent stem cell-like cells in the vertebrate body, including the testis, are the pericytes. The pericytes are derivate of the embryonal epiblast and retain its pluripotency within the microvascular niches where they are disseminated during the embryo- and fetogenesis and are stored as a resting adult stem cell population for tissue generation, maintenance, repair and regeneration. The pluripotency of the epiblast and the pericytes themselves are responsible and explain the neural features of the Leydig cells. Thus, both NCSCs and PMCs are not the ancestors of the pericytes, respectively of the Leydig cells. Biomed Rev 2017; 28: 1-21.Keywords: Leydig cells, origin, microvascular pericytes, smooth muscle cells, Leydig stem cell