The genetic basis of male infertility

Amongst men who attend fertility problems clinics, just over 10% are diagnosed to be oligospermic (< 5 × 106 sperm per ml) or azoospermic, with no known aetiological explanation. Amongst the many possible causes of impaired sperm production there is a genetic component, a pointer to the possible location of some of the responsible genes being found in 1976 when Tiepolo and Zuffardi discovered six azoospermic individuals with a deleted Y chromosome. In each individual, the long arm of the Y chromosome had lost its distal fluorescent segment as well as part of the nonfluorescent euchromatin lying proximal to it (Figure 1). They hypothesized that factors important in spermatogenesis might lie at the interface between fluorescent and nonfluorescent material. The locus, AZFor ‘azoospermia factor’, was subsequently mapped, using collections of deleted Y chromosomes, to interval six of the long arm and it lies within cytological band Yq11.23 (Figure 2).