An investigation of bortezomib effects on mouse preimplantation embryo development in vitro

In this thesis, we aimed to understand and investigate the effect of bortezomib, a selective 26S proteosome inhibitor that commonly used in cancer therapy, on preimplantation embryo development in mice. For this purpose, two cell stage embryos were flushed from mated female CD1 mice and were cultured to specified stages in KSOM medium at 37 °C with 5 % CO2 in humidified air incubator. Two cell stage embryos were exposed to different concentrations (2nM, 3nM,4nM, 5nM,10nM and 20nM) of bortezomib through 1th to 4th day of preimplantation development. We also exposed 3nM, 5nM and 10nM at 2 cell, 8 cell and morula stage separately. Morphologic alterations of the embryos were evaluated by inverted microscopy and the datas were statistically analyzed. The present study showed that bortezomib exposure caused a statistically significant decrease in embryo viability and embryo development due to dose and time. We analized that when embryonic stage progresses, the percentage of formation of next stage embryo was increased. Moreover, it was observed that embryo fragmentation increased at various stages of embryos depending on higher dose and time suggesting that bortezomib induce apoptosis during early embryo development. Furthermore, 20nM bortezomib exposed at 2 cell stage embryo group showed there was an arrested embryos when compared with control groups. Because there is no information in the literature about whether bortezomib has any effect on preimplantation embryo development, we hope that the data obtained from this thesis will make a unique and significant contribution to the literature in this field.