The A-type cyclins and the meiotic cell cycle in mammalian male germ cells.
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.
Department of Genetics & Development, Institute of Human Nutrition, Center for Reproductive Sciences, and The Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, New York, NY 10032, USA. djw3@columbia.edu
Debra J
DJ
Wolgemuth
Karen M
KM
Lele
Vaidehi
V
Jobanputra
Glicella
G
Salazar
D000818:Animals; D019925:Cyclin A / Q000502:physiology*; D056750:Cyclin A1; D056751:Cyclin A2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D006801:Humans; D007248:Infertility, Male / Q000503:physiopathology; D008297:Male; D008540:Meiosis / Q000502:physiology*; D051379:Mice; D013090:Spermatocytes / Q000166:cytology*
C503745:CCNA1 protein, human; C503721:CCNA2 protein, human; C503747:Ccna1 protein, mouse; D019925:Cyclin A; D056750:Cyclin A1; D056751:Cyclin A2; D018844:Cyclin-Dependent Kinases