p66Shc is associated with hydrogen peroxide-induced oxidative stress in preimplantation sheep embryos.

The low efficiency of in vitro embryo production is associated with oxidative stress induced by suboptimal culture conditions. p66Shc is a 66-kDa protein of the ShcA (Src homologous-collagen homolog) adaptor protein family, which is involved in signaling pathways involved in oxidative stress regulation, apoptosis induction, and aging. However, the functional role of p66Shc during the preimplantation development of sheep embryos is not understood. Our results showed that early-cleavage (≤28 hr) embryos had a higher developmental potential than late-cleavage (>28 hr) embryos. The poor quality of these late-cleavage embryos was associated with increased the transcripts and protein of p66Shc and decreased mitochondrial activity. In addition, exogenous hydrogen peroxide-induced oxidative stress significantly increased p66Shc protein abundance and suppressed embryonic development, which was ameliorated by antioxidant treatment. Notably, oxidative stress induced the nuclear localization of p66Shc and phosphorylated (Ser-36) p66Shc. Collectively, these observations suggest that p66Shc may be playing an important role in the regulation of oxidative stress during the preimplantation development of sheep embryos.