Induction of apoptosis involving multiple pathways is a primary response to cyclin A1-deficiency in male meiosis

Authors

  • Glicella Salazar,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
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  • Ayesha Joshi,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
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  • Dong Liu,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
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  • Hongquan Wei,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
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  • Jenny Liao Persson,

    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
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  • Debra J. Wolgemuth

    Corresponding author
    1. Departments of Genetics & Development and Obstetrics & Gynecology, Institute of Human Nutrition, Center for Reproductive Sciences, and Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, New York, New York
    • Herbert Irving Comprehensive Cancer Center, Columbia University Medical Center, College of Physicians & Surgeons, 630 West 168th Street, New York, NY 10032
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Abstract

The meiotic arrest in male mice null for the cyclin A1 gene (Ccna1) was associated with apoptosis of spermatocytes. To determine whether the apoptosis in spermatocytes was triggered in response to the arrest at G2/M phase, as opposed to being a secondary response to overall disruption of spermatogenesis, we examined testes during the first wave of spermatogenesis by terminal deoxynucleotidyl transferase–mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) staining. We observed enhanced apoptosis coinciding with the arrest point in postnatal day 22 tubules, with no overt degeneration. Along with activation of caspase-3, an increase in the levels and change of subcellular localization of Bax protein was observed in cyclin A1–deficient spermatocytes, which coincided with the detection of apoptosis. As p53 is implicated in the activation of Bax-mediated cell death, we generated mice lacking both cyclin A1 and p53. Although the absence of p53 did not rescue the meiotic arrest, there was a decrease in the number of apoptotic cells in the double-mutant testes. This finding suggested that p53 may be involved in the process by which the arrested germ cells are removed from the seminiferous tubules but that other pathways function as well to ensure removal of the arrested spermatocytes. Developmental Dynamics 234:114–123, 2005. © 2005 Wiley-Liss, Inc.

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