Effects of bortezomib on mouse preimplantation embryo development in vitro.

Abstract

Bortezomib, a selective inhibitor of 26S proteasome, is commonly used as a chemotherapeutic agent against different types of human cancer cells. While cancer during pregnancy is a rare condition, the trends in becoming pregnant at an advanced age increase the risk of cancer associated with pregnancy. Cancers need to be treated carefully without harming the fetus during pregnancy for the patients who desire to continue their pregnancy. The aim of this study is to demonstrate the potential side effects of bortezomib as this drug has so far not been investigated during preimplantation embryo development. Two cell stage embryos were flushed from mated female CD1 mice and were cultured. Two-cell, eight-cell, and morula stage embryos were exposed to different concentrations of bortezomib in vitro. Morphologic alterations of the embryos were evaluated and the data were statistically analyzed. Our study showed that bortezomib exposure caused a statistically significant decrease in embryo survival and developmental competence and potential rate. We detected those early stages of embryos are more susceptible to bortezomib exposure than later stages. We indicated that bortezomib adversely affects preimplantation embryo development in a dose, time, and developmental stage dependent manner. Moreover, bortezomib treatment inhibits preimplantation embryo development and induces cytoplasmic fragmentation and cell-cycle arrest on embryos.