Hypothesis: sex determination and germline formation are committed at the pronucleate stage in mammalian embryos

Sex determination in mammals has been defined as those events that fix the nature of the germ cell and the gonad, while other processes influencing sexual form and function such as hormone action constitute sex differentiation (Austin et al., 1981). Such determination involves the separation of germline and soma, controlled initially by maternal genes and then by the zygotic genome after fertilization and early cleavage (Braude et al., 1988). A cascade of events in the genital ridge initiates the differentiation of the gonads and secondary sex characteristics. In this article, we correlate embryological and genetic evidence and propose that germline could be allocated by the 4-cell stage and regulated by oocyte polarity, controlled cleavage planes and early transcription of sex-determining genes from pronuclear stages. Subsequent steps including germline segregation in early embryos and migration of primordial germ cells, and their possible role in the initiation of gonadal sex differentiation in the genital ridge are discussed.