Introduction

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.

Y chromosome

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.

Azoospermia factor

The postulation that deletions in the long arm of the Y chromosome cause azoospermia was made 30 years ago (Tiepolo and Zuffardi, 1976).