The germline is unique among tissues in being the only lineage that is transmitted through generations. The gonadal somatic cells that interact with male and female germ cells are equally important for their juxtacrine and paracrine signalling pathways that lead to the formation of functionally mature gametes and healthy progeny. The present review summarises exciting new studies that our group and others have achieved at the frontier of male and female germ cell biology and in studying transforming growth factor-β signalling pathways in oocyte–somatic cell interactions and gonadal growth and differentiation. In the process, we have produced over 70 transgenic and knockout models to study reproduction in vivo. These models have helped us identify novel and unexplored areas of germ cell biology and translate this work into the fertility clinic.