Modulation of Preimplantation Embryonic Development by Antisense Oligonucleotides to Major Histocompatibility Complex Genes1

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Abstract
The Ped (preimplantation embryo development) gene, which controls the rate of mouse preimplantation embryonic cleavage division and subsequent survival of the embryo, maps to the Q region of the MHC (major histocompatibility complex). Mouse embryos were treated with antisense oligonucleotides to mRNA for the Q region genes Q7/Q9, each of which encodes the Qa-2 antigen. The reverse transcription polymerase chain reaction (RT-PCR) was used to show that antisense treatment, but not sense treatment, decreased the level of mRNA for Qa-2 antigen in preimplantation embryos. Furthermore, both the expression of Qa-2 protein and the rate of embryonic cleavage division were decreased by treatment with antisense but not sense oligonucleotides. These results provide direct evidence that the Ped gene phenotype is at least partially encoded by the Q7/Q9 genes. It is likely that the mouse Ped gene has a human homolog, perhaps within HLA-F. Identification of genes--such as the Ped gene--that affect survival of the embryo may be vitally important for the enhancement of animal and human reproductive success.

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