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This chapter discusses the development of the adult population of Leydig cells from the stem cell precursor through the progenitor and immature Leydig cell stages. The morphogenetic events of early testis differentiation are controlled by the Sry (sex-determining region on the Y chromosome) gene. Lack of luteinizing hormone (LH) stimulation results in reduced steroidogenic enzyme activities and in Leydig cell atrophy. As men age, progressive decreases in serum concentrations of testosterone occur. Associated with these decreases are significant health consequences, including reduced sexual function, energy, muscle function, and bone density, and increased frailty and cognitive impairment. A number of hypotheses have been put forward over the years to explain changes that occur in aging cells, including late-onset gene expression, telomere shortening, gene modifications, changes in the immune system, and accumulated reactive oxygen-induced damage to DNA, lipids, and/or proteins.