Ped gene expression by embryos cultured in vitro.

The rate of cleavage division of preimplantation mouse embryos has been shown to be influenced by the Ped gene, a gene linked to the H-2 complex, the major histocompatibility complex of the mouse. There are two functional alleles of the Ped gene, slow and fast. To examine Ped gene expression outside of the maternal uterine environment, embryos from inbred and congenic mouse strains were cultured in vitro, in chemically defined medium, for various lengths of time. The results of these studies show that the difference in the rate of cleavage division between slow-developing strains (Ped slow) and fast-developing strains (Ped fast) is maintained in vitro. Thus, the Ped gene phenotype of developing embryos is an intrinsic property of the embryos themselves. INTRODUCT ION The timing of preimplantation development is crucial for the survival of the mammalian embryo. A close degree of synchronization is necessary between the development of the embryo and of the uterus if implantation and subsequent fetal development is to be successful. McLaren and Michie (1956) showed that mouse embryos transferred to a uterus at an earlier stage of development wait for the uterus to catch up developmentally before implanting, whereas embryos transferred to a uterus at a later stage of development die. Using embryo transfer experiments, Doyle et al. (1963) found that embryos 1-2 days older than the uterus survived, whereas embryos younger than the uterus had retarded cleavage rates and eventually, they fragmented and died. Embryonic and fetal development in the mouse takes approximately 20 days, of which 4.5 days are spent as a free-floating, independent embryo, first in the oviducts and then in the uterus. During this preimplantation period, the embryo undergoes a series of cleavage divisions defining six stages of development: oocyte, 2-cell, 4-cell, 8-cell, morulae, and blastocyst. At the late 2-cell to 4-cell stages,