PMID- 22949597 OWN - NLM STAT- MEDLINE DCOM- 20130116 LR - 20161125 IS - 1791-7549 (Electronic) IS - 0258-851X (Linking) VI - 26 IP - 5 DP - 2012 Sep-Oct TI - Doxorubicin induces early embryo apoptosis by inhibiting poly(ADP ribose) polymerase. PG - 827-34 AB - BACKGROUND: The effect of Doxorubicin, a widely used chemotherapeutic agent, on early mouse embryonic development has not been previously characterized. MATERIALS AND METHODS: Expression of apoptosis-related genes and poly(ADP-ribose) polymerase (PARP) family genes were assessed by real-time reverse transcription polymerase chain reaction (RT-PCR). Apoptosis in mouse blastocysts was tested using the terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. Cleaved (c)-PARP was analyzed by western blot. RESULTS: A 20 h exposure to doxorubicin caused rapid cytoplasmic fragmentation, DNA condensation and disruption of the cytoskeleton in mouse embryos. Doxorubicin altered the expression of genes involved in DNA repair and apoptosis and blocked early embryonic development, suggesting that doxorubicin affects DNA synthesis and repair. Furthermore, the effect of doxorubicin on early embryo development was determined by assessing the rates of development to different stages and an apoptosis index. Both assays confirmed that doxorubicin altered embryonic development. In conclusion, doxorubicin blocked pre-implantation development in early mouse embryos by altering apoptosis-related gene expression and inactivating DNA repair by PARP. FAU - Wang, Qing-Ling AU - Wang QL AD - Department of Animal Sciences, Chungbuk National University, Chungbuk, Cheongju 361-763, South Korea. FAU - Sun, Shao-Chen AU - Sun SC FAU - Han, Jemesbond AU - Han J FAU - Kwak, Yong-Chul AU - Kwak YC FAU - Kim, Nam-Hyung AU - Kim NH FAU - Cui, Xiang-Shun AU - Cui XS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Greece TA - In Vivo JT - In vivo (Athens, Greece) JID - 8806809 RN - 0 (Antibiotics, Antineoplastic) RN - 0 (Poly(ADP-ribose) Polymerase Inhibitors) RN - 80168379AG (Doxorubicin) RN - EC 2.4.2.30 (Parp1 protein, mouse) RN - EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1) RN - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases) SB - IM MH - Animals MH - Antibiotics, Antineoplastic/*pharmacology MH - Apoptosis/*drug effects MH - Blastocyst/cytology/*drug effects/enzymology MH - DNA Damage MH - Doxorubicin/*pharmacology MH - Embryo Culture Techniques MH - Female MH - Mice MH - Mice, Inbred ICR MH - Poly (ADP-Ribose) Polymerase-1 MH - *Poly(ADP-ribose) Polymerase Inhibitors MH - Poly(ADP-ribose) Polymerases/metabolism MH - Zygote/cytology/drug effects EDAT- 2012/09/06 06:00 MHDA- 2013/01/17 06:00 CRDT- 2012/09/06 06:00 PHST- 2012/09/06 06:00 [entrez] PHST- 2012/09/06 06:00 [pubmed] PHST- 2013/01/17 06:00 [medline] AID - 26/5/827 [pii] PST - ppublish SO - In Vivo. 2012 Sep-Oct;26(5):827-34.