Induction of apoptosis involving multiple pathways is a primary response to cyclin A1-deficiency in male meiosis.
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.
Salazar
Glicella
G
Department of Genetics & Development, Institute of Human Nutrition, Center for Reproductive Sciences, Columbia University Medical Center, College of Physicians & Surgeons, New York, NY10032, USA.
Joshi
Ayesha
A
Liu
Dong
D
Wei
Hongquan
H
Persson
Jenny Liao
JL
Wolgemuth
Debra J
DJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053938:DNA Fragmentation; D005786:Gene Expression Regulation / Q000502:physiology; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D008540:Meiosis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013090:Spermatocytes / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
D016159:Tumor Suppressor Protein p53; D053148:Caspase 3