Sex determination: lessons from families and embryos
Human sex determination is a family affair. The sex of the offspring is usually determined by the sex chromosomal inheritance from fathers. Some large families have an excess of male or female offspring and the stochastic nature of fertilization can explain this phenomenon. In other families, deviation of the sex ratio from unity can be explained by aberrant gonadal and genital developments that are caused by heritable mutations or chromosomal imbalances. In some instances, analysis of these families has contributed to the identification of sex-determining genes and their modifiers. Although many of these cases become apparent in infancy when the children are born with ambiguous genitalia, others become apparent in adolescence or adulthood when affected individuals fail to go into puberty or to have menstrual cycles. Sex determination is an also embryonic affair. Many of the key events in sex determination and development involve autonomous cellular differentiation, endocrine and paracrine cell signalling and cell migration. Comparison of gene expression patterns in human embryos and embryos from other vertebrate species has demonstrated a similar repertoire that differs principally with respect to timing of expression. Predictions about the natural history and transmission of sex determination disorders have been based on an understanding of the genetic mechanisms of sex determination. Recommendations for the treatment of these conditions have been developed from the understanding of the natural history, although the issue of gender reassignment early in life continues to be much debated.