Endocrine Abstracts (2011) 26 S11.1

Update on genetics in male infertility

Alberto Ferlin


University of Padova, Padova, Italy.


Despite spermatogenesis is among the most finely regulated processes in our body, few genetic tests are currently routinely used in infertile males. These include analysis of karyotype, Yq microdeletions, CFTR and androgen receptor gene mutations, which collectively account for 15–20% of male infertility. Very little is known about the pathogenic mechanism leading to spermatogenesis disruption in many of these patients, especially those carrying Yq microdeletions. Recent field of research of our group focused on the identification of molecular pathways leading to spermatogenic damage in men with AZFc microdeletions and idiopathic infertility. Testicular gene expression profiling carried out by microarray assay revealed that all the AZFc deleted samples clustered together and showed a downregulation of several genes (331) related to spermatogenesis. Interestingly, some idiopathic patients clustered together to AZFc-deleted patients, suggesting that several forms of infertility can be triggered by a common pathogenic mechanism that is likely related to alterations in testicular mRNA storage. Our data suggest that a lack of testicular DAZ gene expression may be the trigger of such mechanism and DAZ gene dysfunctions could therefore account for a larger number of previously thought ‘idiopathic’ infertility cases. A second line of research includes the contribution of genetic polymorphisms to male infertility and, more importantly, as markers for a pharmacogenomic approach to the treatment of infertile males. In this light, we demonstrated the diagnostic and therapeutical validity of polymorphisms in the FSH receptor and FSH beta genes. These results, taken together with the most recent research published on the genetics of male infertility are shedding light on novel molecular events involved in ‘old’ causes of male infertility and are suggesting new pathogenetic mechanisms of spermatogenesis disruption. It is believable that new genetic tests could be in a near future introduced in the clinical practice as diagnostic, susceptibility or pharmacogenetic tests.

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