earticle

영어

Doxorubicin, a widely used chemotherapeutic agent, were found rapidly undergo morphological and biochemical changes via discrete effector signaling pathways consistent with the occurrence of apoptosis of oocyte. In this report, we elucidated the molecular requirements for actions of this drug in early embryos. Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues have recently been shown in female oocyte cells. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Cleaved PARP (cPARP) may be considered a marker of apoptosis. Doxorubicin inhibited the early embryo development, but the treatment could still reach the BL (blastocyst) stage that suggested that involved in DNA synthesis and repaired progress. Herein, the higher expression of PARP family shown especially in 2, 4 cell stagy. There was evidence of expression of Caspase3 and Bcl2l1 during embryogenesis (2 cell, 4 cell, morula and BL stage), suggesting that modulations of apoptosis-related genes and PARP were cause by DXR. Furthermore, the effect of doxorubicin on early embryo development was assessed different stage rates, and apoptosis index also conformed doxorubicin modulate embryo development by regulating apoptosis-related genes and PARP family genes. In conclusion, Doxorubicin blocked pre-implantation development in early mouse embryos by altering apoptosis-related gene expression and inactivating DNA repair by Parp.