TY - JOUR
T1 - Premeiotic germ cell defect in seminiferous tubules of Atm-null testis
AU - Takubo, Keiyo
AU - Hirao, Atsushi
AU - Ohmura, Masako
AU - Azuma, Masaki
AU - Arai, Fumio
AU - Nagamatsu, Go
AU - Suda, Toshio
PY - 2006/12/29
Y1 - 2006/12/29
N2 - Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16Ink4a-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16Ink4a-mediated senescence.
AB - Lifelong spermatogenesis is maintained by coordinated sequential processes including self-renewal of stem cells, proliferation of spermatogonial cells, meiotic division, and spermiogenesis. It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell maintenance. ATM is activated in premeiotic spermatogonial cells and the Atm-null testis shows progressive degeneration. In Atm-null testicular cells, differing from bone marrow cells of Atm-null mice, reactive oxygen species-mediated p16Ink4a activation does not occur in Atm-null premeiotic germ cells, which suggests the involvement of different signaling pathways from bone marrow defects. Although Atm-null bone marrow undergoes p16Ink4a-mediated cellular senescence program, Atm-null premeiotic germ cells exhibited cell cycle arrest and apoptotic elimination of premeiotic germ cells, which is different from p16Ink4a-mediated senescence.
KW - ATM
KW - Apoptosis
KW - Cell cycle arrest
KW - Premeiotic germ cells
UR - http://www.scopus.com/inward/record.url?scp=33750806537&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750806537&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2006.10.145
DO - 10.1016/j.bbrc.2006.10.145
M3 - Article
C2 - 17097049
AN - SCOPUS:33750806537
VL - 351
SP - 993
EP - 998
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 4
ER -