Adrenals and gonads both emerge from a common embryonic structure referred to as the adreno-gonadal primordium (AGP). Insulin-like growth factors (IGFs) provide essential signals for the control of embryonic development. We showed that the in vivo deletion of both Insr and Igf1r is sufficient to induce a complete XY male-to-female sex reversal phenotype due to a failure of upregulating Sry and the subsequent testicular genetic program. In XX and XY mutant gonads, we observed a delay in ovarian differentiation and germ cell entry into meiosis as well as a complete absence of adrenal gland. Later, Sertoli cells (SCs), the only somatic constituents of the seminiferous epithelium are mainly committed to sustain spermatogenesis. Importantly, the final testis size, the number of germ cell in the adult testis and the sperm output are directly linked to the total number of Sertoli cells. We also demonstrated that mice lacking both Insr and Igf1r specifically in Sertoli cells display a reduction of testicular weight, Sertoli cell number, tubule's length and sperm output by over 70%, probably due to a massive apoptotic wave during the period of perinatal proliferation (P5).