The A-type cyclins and the meiotic cell cycle in mammalian male germ cells

Authors

  • Debra J. Wolgemuth,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
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  • Karen M. Lele,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
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  • Vaidehi Jobanputra,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
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  • Glicella Salazar

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY, USA
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  • This is a review for the EAA International Symposium on ‘Genetics of male infertility: from research to clinic’, Florence, Italy.

Dr Debra J. Wolgemuth, Departments of Genetics & Development and Obstetrics & Gynecology, Columbia University Medical Center, 630 West 168th Street, New York, NY 10032, USA. E-mail: djw3@columbia.edu.

Summary

There are two mammalian A-type cyclins, cyclin Al and A2. While cyclin A1 is limited to male germ cells, cyclin A2 is widely expressed. Cyclin A2 promotes both Gl/S and G2/M transitions in somatic cells and cyclin A2-deficient mice are early embryonic lethal. We have shown that cyclin Al is essential for passage of spermatocytes into meiosis I (MI) by generating mice null for the cyclin A1 gene Ccna1. Both Ccna1−/− males and females were healthy but the males were sterile because of a cell cycle arrest before MI. This arrest was associated with desynapsis abnormalities, low M-phase promoting factor activity, and apoptosis. We have now determined that human cyclin A1 is expressed in similar stages of spermatogenesis and are exploring its role in human male infertility and whether it may be a novel target for new approaches for male contraception.

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