SFEBES2013 Symposia Hormone Maketh Man (3 abstracts)
University of Geneva, Geneva, Switzerland.
The way to maleness is a long process starting with fertilization when sperm delivers the testis-determining Y chromosome to the oocyte and ending with puberty and the action of testicular hormones. Since Sertoli cells are at the crossroads of the entire process, the analysis of the factors driving their differentiation and function is essential to the global understanding of male sexual development. By using mouse functional genetics, we will show that growth factors of the insulin/IGF family are required to mediate different aspects of gonadal development including Sertoli cell differentiation and function. Constitutive ablation of insulin/IGF signaling pathway led to defects in sex determination including absence Sertoli cell commitment and testicular differentiation as well as a delay in ovarian differentiation. In addition, we also show that the growth factors of the insulin family are the major drivers regulating the final number of Sertoli cells, testis size and daily sperm output in mice. These findings shed light on a crucial but so far underestimated signaling pathway underlying male sexual development in mice and potentially disorders of sex development (DSD) in humans.
Declaration of funding
This work was supported by the Swiss National Science Foundation, The Gerbert Rüf Stiftung and NCCR frontiers in genetics.