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Male infertility: role of genetic background

  • Alberto Ferlin
    Affiliations
    University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova
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  • Florina Raicu
    Affiliations
    G. d'Annunzio University Foundation, Department of Clinical Sciences and Bioimaging, Pescara Hospital, Pescara, Italy

    G. d'Annunzio University Foundation, Ageing Research Centre, Pescara Hospital, Pescara, Italy
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  • Valentina Gatta
    Affiliations
    G. d'Annunzio University Foundation, Ageing Research Centre, Pescara Hospital, Pescara, Italy

    G. d'Annunzio University Foundation, Department of Biomedical Sciences, Chieti, Pescara Hospital, Pescara, Italy
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  • Daniela Zuccarello
    Affiliations
    University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova
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  • Giandomenico Palka
    Affiliations
    G. d'Annunzio University Foundation, Department of Biomedical Sciences, Chieti, Pescara Hospital, Pescara, Italy

    Human Genetics Division, Pescara Hospital, Pescara, Italy
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  • Carlo Foresta
    Correspondence
    Correspondence: Tel: +39 049 8218517; Fax: +39 049 8218520
    Affiliations
    University of Padova, Department of Histology, Microbiology and Medical Biotechnologies, Centre for Male Gamete Cryopreservation, Via Gabelli 63, 35121 Padova
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      Abstract

      Male infertility represents one of the clearest examples of a complex disease with a substantial genetic basis. Numerous male mouse models, mutation screening and association studies reported over the last few years reveal the high prevalence of genetic causes of spermatogenic impairment, accounting for 10–15% of severe male infertility, including chromosomal aberrations and single gene mutations. Natural selection prevents the transmission of mutations causing infertility, but this protective mechanism may be overcome by assisted reproduction techniques. Consequently, the identification of genetic factors is important for appropriate management of the infertile couple. However, a large proportion of infertile males are diagnosed as idiopathic, reflecting poor understanding of the basic mechanisms regulating spermatogenesis and sperm function. Furthermore, the molecular mechanisms underlying spermatogenic damage in cases of genetic infertility (for example Yq microdeletions) are not known. These problems can be addressed only by large scale association studies and testicular or spermatozoal expression studies in well-defined alterations of spermatogenesis. It is conceivable that these studies will have important diagnostic and therapeutic implications in the future. This review discusses the genetic causes of male infertility known to date, the genetic polymorphisms possibly associated with male infertility, and reports novel results of global gene expression profiling of normal human testis by microarray technology.

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      Biography

      Alberto Ferlin, MD, PhD, is a researcher and clinician at the Department of Histology, Microbiology and Medical Biotechnologies of the University of Padova and at the Centre for Male Gamete Cryopreservation under the direction of Carlo Foresta. His research activity focuses on male reproduction and spermatogenesis. Primary research concerns the Y chromosome, androgen receptor and INSL3. He is author of over 80 published papers, invited speaker to many scientific congresses, and winner of awards from international congresses and societies. He is secretary of the Italian Society of Physiopathology of Reproduction and member of the scientific committee of the Italian Society of Medical Andrology.