Published online by Cambridge University Press: 14 August 2009
Although abnormalities of the Y chromosome have been associated with male infertility since 1976 (Tiepolo and Zuffardi, 1976), it was only in the last decade that the Y chromosome was shown to have regions and genes that govern spermatogenesis. More recently, it has become clear that the X chromosome may be just as important as the Y chromosome in determining male fertility potential. This chapter will review our current understanding of the genotype–phenotype relationships that underlie abnormalities of both the X and Y chromosomes, and discuss recognized syndromes of the gonosomes that are known to cause male infertility.
Over the last 10 years, there has been significant progress both in analyzing the molecular structure of the Y chromosome and understanding the relationship of Y chromosome mutations to infertility phenotypes. Before its firm association with male fertility, the Y chromosome was widely considered a genetic black hole, a chromosome that evolved as a broken remnant of the X chromosome. It was clear that the Y harbored the male sex-determining region (testis-determining region or sex-determining region Y (SRY)), but it was also home to gene regions that govern stature, tooth enamel and hairy ears as well as ‘junk’ gene regions. Now that the genome of the human Y is known, we realize that this chromosome is structurally unique as a fertility chromosome.
The postulation that deletions in the long arm of the Y chromosome cause azoospermia was made 30 years ago (Tiepolo and Zuffardi, 1976).