Progenitor cells of the testosterone-producing Leydig cells revealed

Abstract

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.

Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells

“…It is unclear if the complete population of COUP-TFII-expressing stem cells can develop into adult Leydig cells or only a subpopulation, because only a proportion of the stem cells switched on GATA4 or PDGFRα after EDS. Previous studies suggested that adult Leydig cells could originate from other interstitial cell types, such as peritubular myoid cells, pericytes, endothelial cells, or macrophages (24,29,(54)(55)(56). Using specific markers for these cell types and the EDS model, we found no evidence for coexpression of COUP-TFII in these cell types.…”

Regulation of seminiferous tubule-associated stem Leydig cells in adult rat testes

“…Cells on the tubule surfaces first underwent division, and then differentiated and produced T (17). These results suggested that in addition to reported perivascular locations in the interstitial compartment (18), stem cells also were located on the surfaces of the seminiferous tubules (16,19,20).…”

“…The isolation of pure stem cells requires specific cell surface markers. Several proteins had been reported in previous studies to be expressed by stem Leydig cells in neonatal or adult testes, including nestin (11,18), COUP-TFII (24,34), Arx (35), CD51 (11), p75NTR (11), and PDGFRα (9,10,16). Nestin, COUP-TFII, and Arx are intracellular proteins and, therefore, could not readily be used as markers to purify the cells.…”

“…----+ ----+ ----+ We now know that stem Leydig cells are located both on the tubule surfaces (9,16,19,20) and associated with blood vessels (18,24). In the event of loss of the adult Leydig cells (14,15), stem cells in both locations are capable of regenerating new Leydig cells (16,(20)(21)(22); Fig.…”

Malignant Leydig Cell Tumor with Spindle-Shaped Cells in a Male CD-1 Mouse

“…The progenitors of spindle to ovalshaped cells differentiate into hypertrophic fetal-type Leydig cells [5,16]. Davidoff et al proposed that progenitor cells positive for nestin-a stem/progenitor cell marker of the nervous system-are localized in vascular walls, where aSMA-positive vascular smooth muscle cells and pericytes function as the progenitors of Leydig cells [2]. They showed that these progenitor cells protrude from the vessel walls, accumulate in the vicinity of the vessel walls, and form Leydig cell clusters; these processes are accompanied by a loss of immunoreactivity toward aSMA.…”