Programmed cell death during mammalian preimplantation embryo development, genetic regulation and developmental consequences

grantor: University of TorontoThe quality of embryos produced by 'In Vitro' Fertilization (IVF) is variable. Many embryos contain unequal-sized blastomeres and multiple cellular fragments. The objective of my work was to determine if apoptosis could be observed in human preimplantation embryos and further explore genetic and molecular mechanisms regulating cell death during early embryo development. Electron microscopy as well as chromatin labelling confirmed the typical morphological features of apoptosis in fragmented human embryos. In a mouse model, maternal age beyond 40 weeks increased the rate of embryo fragmentation following IVF, but oocytes from females of all ages had a uniformly high rate of fragmentation when fertilized 'in vitro'. Furthermore, in mice IVF significantly reduced the rate of blastocyst formation and decreased the mean cell number at the blastocyst stage in comparison with embryos produced in vivo. The temporal expression patterns of several cell death regulatory genes was assessed during murine and human embryo development, and showed that the expression of these genes is altered in mouse embryos undergoing fragmentation. This data are consistent with hypothesis that programmed cell death may occur by default in embryos which fail to execute essential developmental events during the first cell cycle and this process is actively regulated via expression of cell death regulatory genes.Ph.D