Knockdown of p66Shc by siRNA injection rescues arsenite-induced developmental retardation in mouse preimplantation embryos.

ABSTRACT

Two-cell arrest plays a principal role in the elevated levels of embryo loss during the first week of development in mouse. Previously, we have shown that arsenic can apparently induce 2-cell arrest in mouse preimplantation embryo and the expression of oxidative stress adaptor protein p66(Shc) is up-regulated in this process. In the present study, we demonstrated that microinjection of p66(Shc) siRNA into the pronucleus of zygotes resulted in a markedly decrease in both mRNA and protein levels of p66(Shc). The arsenite-induced 2-cell arrests, along with a reduction in the levels of reactive oxygen species (ROS), were significantly inhibited and the number of embryos developing to morula stage concurrently increased upon p66(shc) siRNA microinjection. These findings indicate that knockdown of p66(shc) improves the developmental competence of arsenite-exposed embryos in vitro by increasing the resistance to oxidative stress. In addition, we highlight the utility of single-embryo analysis in preimplantation embryos.