Development of fetal and adult Leydig cells

Background: In mammals, two distinct Leydig cell populations, fetal Leydig cells (FLCs) and adult Leydig cells (ALCs), appear in the prenatal and postnatal testis, respectively. Although the functional differences between these cell types have been well described, the developmental relationship between FLCs and ALCs has not been fully understood. In this review, I focus on the cellular origins of FLCs and ALCs as well as the developmental and functional links between them. Methods: I surveyed previous reports about FLC and/or ALC development and summarized the findings. Main findings: Fetal Leydig cells and ALCs were identified to have separate origins in the fetal and neonatal testis, respectively. However, several studies suggested that FLCs and ALCs share a common progenitor pool. Moreover, perturbation of FLC development at the fetal stage induces ALC dysfunction in adults, suggesting a functional link between FLCs and ALCs. Although the lineage relationship between FLCs and ALCs remains controversial, a recent study suggested that some FLCs dedifferentiate at the fetal stage, and that these cells serve as ALC stem cells. Conclusion: Findings obtained from animal studies might provide clues to the causative mechanisms of male reproductive dysfunctions such as testicular dysgenesis syndrome in humans.