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 cells