Azoospermia and genetic mutations: implications for the methods of in vitro fertilization

Much evidence suggests the fundamental role of the Y chromosome during spermatogenesis. Especially, a gene on the long arm (localized in a portion of the chromosome called Yq11), the AZF (azoospermic factor), is necessary for the achievement and the maintenance of the spermatogenetic process. In fact mutations and deletions in this part of the chromosome inevitably cause severe oligozoospermia or azoospermia. Furthermore other genes on the short arm seem to have a role during spermatogenesis: they are called ZFY (zink finger Y, which encodes a DNA binding protein) and TSPY (expressed in the spermatids nuclei); but the function of these genes is still uncertain, since at this moment no deletions or mutations have been found at this level. Further genes only recently cloned include the CREM (cAMP-responsive element modulator), whose mutation causes azoospermia with a spermatidic arrest in the mouse, and the complex c-kit/Steel-factor. The latter is essential for spermatogonial proliferation and differentiation, so that an alteration at this level can determine spermatogonial arrest or the absence of germinal cells with the presence of Sertoli cells only (Sertoli cells only syndrome). In contrast with AZF, both the CREM gene and c-kit/Steel-factor genes are autosomal (chromosome 10 for the CREM, 4 for c-kit, 1 for Steel-factor, respectively). Several genes may be involved in the spermatogenetic process, but their role, excepting for AZF, is still unclear.