Gene polymorphisms/mutations relevant to abnormal spermatogenesis

Abstract

Despite the identification of an increasing number of candidate genes involved in spermatogenesis, the armamentarium of diagnostic genetic tests in male infertility remains extremely limited. A number of new causative mutations have been reported for hypogonadotrophic hypogonadism but still the genetic diagnosis in this pathological condition is made only in about 20% of cases. The sole molecular genetic test that is routinely proposed in severe spermatogenic disturbances is screening for Yq microdeletion. The search for causative mutations in the Y chromosome, and in autosomal and X-linked genes, has mostly been unsuccessful. The paucity of gene mutations raises questions about the appropriateness of the currently used screening approaches. Among the proposed genetic risk factors, gr/gr deletion of the Y chromosome seems to be the most promising polymorphism. Other polymorphisms are awaiting further confirmation, whereas for some (POLG, DAZL, USP26, FSHR) a lack of association with abnormal spermatogenesis has now been ascertained. It is likely that some polymorphisms lead to testicular dysfunction only when in association with a specific genetic background or with environmental factors. Future large-scale studies with stringent study design may provide a more efficient way to identify clinically relevant genetic factors of male infertility.