Testosterone is widely accepted as the main driver of spermatogenesis, being both necessary and sufficient to drive qualitative sperm development in the absence of stimulation by FSH or LH. As described above, testosterone exerts the majority of its function via binding its cognate receptor AR. AR is expressed in several cell-types of the testis through development and adult life, though importantly it is never expressed in germ cells suggesting the impact of androgens on spermatogenesis is via an indirect signaling route involving the supporting somatic cell lineages. In the mouse, AR expression begins around embryonic day 15 (Scott et al. 2007), and in week 7 of gestation in the human (Shapiro et al. 2005), and localizes to peritubular cells, which continue to express AR throughout life, and cells of the testicular interstitium. After birth AR expression is first detectable in Sertoli cells at postnatal day 4, and continues throughout life. Adult Leydig cell precursors begin to proliferate at postnatal day 12 and switch on AR expression from this point onwards. Thus in the adult testis of both rodents and humans, AR is expressed by Sertoli cells, Leydig cells, Peritubular myoid cells, vascular smooth muscle and vascular endothelial cells, all of which are responsive to androgen stimulation reviewed in (De Gendt and Verhoeven 2012a, b, c; Fig. 4.1a).