1. ¹Kasturba Medical College, Manipal, India
2. ²Kyoto University Radiation Biology Center, Sakyo-ku, Kyoto, Japan
3. ³The Research Institute for Advanced Science and Technology, Osaka Prefecture University, Sakai, Osaka, Japan
4. ⁴Genome Damage Response Research Unit, RIKEN, 2-1 Hirosawa, Wako Saitama, Japan

Correspondence: Professor O Niwa, Department of Late Effect Studies, Radiation Biology Center, Kyoto University, Yoshida konoe, Sakyo-ku, Kyoto, Kyoto 6068501, Japan. E-mail: oniwa@house.rbc.kyoto-u.ac.jp

Received 22 April 2005; Revised 11 January 2007; Accepted 6 February 2007; Published online 9 April 2007.

Abstract

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.