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p21 provides stage specific DNA damage control to preimplantation embryos
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Journal Article
p21 provides stage specific DNA damage control to preimplantation embryos
2007
Overview
The early stage embryogenesis of higher eukaryotes lacks some of the damage response pathways such as G1/S checkpoint, G2/M checkpoint and apoptosis. We examined here the damage response of preimplantation stage embryos after fertilization with 6 Gy irradiated sperm. Sperm-irradiated embryos developed normally for the first 2.5 days, but started to exhibit a developmental delay at day 3.5. p21 was activated in the delayed embryos, which carried numerous micronuclei owing to delayed chromosome instability. Apoptosis was observed predominantly in the inner cell mass of the day 4.0 embryos. Sperm-irradiated p21−/− embryos lacked the delay, but chromosome instability and apoptosis were more pronounced than the corresponding p21 wild-type embryos. We conclude from the result that damage responses come in a stage-specific manner during preimplantation stage development; p53-dependent S checkpoint at the zygote stage, p21-mediated cell cycle arrest at the morula/blastocyst stages and apoptosis after the blastocyst stage in the inner cell mass.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
/ Biological and medical sciences
/ Cancer
/ Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
/ Cyclin-dependent kinase inhibitor p21
/ Cyclin-Dependent Kinase Inhibitor p21 - deficiency
/ Cyclin-Dependent Kinase Inhibitor p21 - genetics
/ Cyclin-Dependent Kinase Inhibitor p21 - physiology
/ Female
/ Fundamental and applied biological sciences. Psychology
/ Genetics
/ Male
/ Medicine
/ Mice
/ Molecular and cellular biology
/ Oncology
/ Sperm
/ Zygotes
