Here, we provide an overview of the effects on follicle-stimulating hormone (FSH), insulin-like growth factor (IGF) system, androgen, and estrogen signaling pathways on Sertoli cells (SC) function and the “niche” microenvironment, and an overview of molecular interference associated with obesity and insulin resistance all within the main signaling pathway involved in the proliferation and maturation of SCs and germ cells (GCs), which could be the basis for establishing a causal relationship between childhood obesity and the risk of reduced sperm count in adulthood. Here, BRD2 is linked to obesity due to melanocortin 4 receptor deficiency.