Heat shock protein 70 (Hsp70) protects postimplantation murine embryos from the embryolethal effects of hyperthermia

Previous work has shown that there is a positive correlation between the in duction of Hsp70 and its transient nuclear localization and the acquisition and loss of induced thermotolerance in postimplantation rat embryos. To de termine whether Hsp70 is sufficient to induce thermotolerance in postimplan tation mammalian embryos, we used a transgenic mouse in which the normally strictly inducible Hsp70 is constitutively expressed in the embryo under th e control of a beta-actin promoter. Day 8.0 mouse embryos heterozygous for the Hsp70 transgene were not protected from the embryotoxic effects of hype rthermia (43 degrees C); however, homozygous embryos, expressing approximat ely twice as much Hsp70 as heterozygous embryos, were partially protected ( increased embryo viability) from the embryolethal effects of hyperthermia, Although the viability of transgenic embryos was significantly increased co mpared with that of nontransgenic embryos, this protection did not extend t o embryo growth and development, To determine whether the failure to achiev e a more robust protection was related to the expression of insufficient Hs p70 in transgenic embryos, we undertook experiments to determine whether th e level of Hsp70 correlated with the level of thermotolerance induced by va rious lengths of a 41 degrees C heat shock. A 41 degrees C, B-minute heat s hock failed to induce Hsp70 or thermotolerance, a 41 degrees C, 15-minute h eat shock induced Hsp70 and a significant level of thermotolerance, while a 41 degrees C, 60-minute heat shock induced an even higher level of Hsp70 a s well as a higher level of thermotolerance. Quantitation of Hsp70 levels i ndicated that thermotolerance was associated with levels of Hsp70 of 820 pg /mu g embryo protein or greater. Subsequent quantitation of the amount of H sp70 expressed in homozygous transgenic embryos indicated a level of 577 pg /mu g embryo protein, that is, a level below that associated with induced t hermotolerance. Overall, results presented indicate that Hsp70 does play a direct role in the induction of thermotolerance in postimplantation mouse e mbryos; however, the level of thermotolerance is dependent on the level of Hsp70 expressed. Dev Dyn 1999;214:159-170, (C) 1999 Wiley-Liss, Inc.