Genetic causes of spermatogenic failure

Abstract

Approximately 10%-15% of couples are infertile, and a male factor is involved in almost half of these cases. This observation is due in part to defects in spermatogenesis, and the underlying causes, including genetic abnormalities, remain largely unknown. Until recently, the only genetic tests used in the diagnosis of male infertility were aimed at detecting the presence of microdeletions of the long arm of the Y chromosome and/or chromosomal abnormalities. Various other single-gene or polygenic defects have been proposed to be involved in male fertility. However, their causative effects often remain unproven. The recent evolution in the development of whole-genome-based techniques and the large-scale analysis of mouse models might help in this process. Through knockout mouse models, at least 388 genes have been shown to be associated with spermatogenesis in mice. However, problems often arise when translating this information from mice to humans.

Figure 1

Distribution of Yq microdeletions among the three AZF regions. AZF, azoospermia factor; Yq, long arm of the Y chromosome.

Figure 2

Scheme of knockout, knockin and gene trapping methodologies. pA, plasminogen activator; SA, splice acceptor; WT, wild type; E, exon.