New Insights into the Regulation of Mammalian Sex Determination and Male Sex Differentiation

Abstract

In mammals, sex development is a genetically and hormonally controlled process that begins with the establishment of chromosomal or genetic sex (XY or XX) at conception. At approximately 6 to 7 weeks of human gestation or embryonic day e11.5 in the mouse, expression of the Y chromosome-linked sex determining gene called SRY (described in detail in this chapter) then initiates gonadal differentiation, which is the formation of either a testis (male) or an ovary (female). Male sex differentiation (development of internal and external reproductive organs and acquisition of male secondary sex characteristics) is then controlled by three principal hormones produced by the testis: Mullerian inhibiting substance (MIS) or anti-Mullerian hormone (AMH), testosterone, and insulin-like factor 3 (INSL3). In the absence of these critical testicular hormones, female sex differentiation ensues. This sequential, three-step process of mammalian sex development is also known as the Jost paradigm. With the advent of modern biotechnologies over the past decade, such as transgenics, array-based gene profiling, and proteomics, the field of mammalian sex determination has witnessed a remarkable boost in the understanding of the genetics and complex molecular mechanisms that regulate this fundamental biological event. Consequently, a number of excellent reviews have been devoted to this topic. The purpose of the present chapter is to provide an overview of selected aspects of mammalian sex determination and differentiation with an emphasis on studies that have marked this field of study.