title: Ochratoxin a inhibits mouse embryonic development by activating a mitochondrion-dependent apoptotic  signaling pathway.
abstract: Ochratoxin A (OTA), a mycotoxin found in many foods worldwide, causes nephrotoxicity, hepatotoxicity, and immunotoxicity, both in vitro and in vivo. In the present study, we explored the cytotoxic effects exerted by OTA on the blastocyst stage of mouse embryos, on subsequent embryonic attachment, on outgrowth in vitro, and following in vivo implantation via embryo transfer. Mouse blastocysts were incubated with or without OTA (1, 5, or 10 μM) for 24 h. Cell proliferation and growth were investigated using dual differential staining; apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay; and embryo implantation and post-implantation development were assessed by examination of in vitro growth and the outcome of in vivo embryo transfer, respectively. Blastocysts treated with 10 μM OTA displayed a significantly increased level of apoptosis and a reduction in total cell number. Interestingly, we observed no marked difference in implantation success rate between OTA-pretreated and control blastocysts either during in vitro embryonic development (following implantation in a fibronectin-coated culture dish) or after in vivo embryo transfer. However, in vitro treatment with 10 μM OTA was associated with increased resorption of post-implantation embryos by the mouse uterus, and decreased fetal weight upon embryo transfer. Our results collectively indicate that in vitro exposure to OTA triggers apoptosis and retards early post-implantation development after transfer of embryos to host mice. In addition, OTA induces  apoptosis-mediated injury of mouse blastocysts, via reactive oxygen species (ROS) generation, and promotes mitochondrion-dependent apoptotic signaling processes that impair subsequent embryonic development.
authors.affiliation: Department of Life Science, National Pingtung University of Science and Technology, Pingtung 912, Taiwan. whchan@cycu.edu.tw.
authors.forename: Yan-Der
authors.initials: YD
authors.lastname: Hsuuw
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
authors.forename: Jau-Song
authors.initials: JS
authors.lastname: Yu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000166:cytology / Q000187:drug effects*; D002273:Carcinogens / Q000633:toxicity; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation; D004624:Embryo Transfer; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D008297:Male; D008813:Mice, Inbred ICR; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D009793:Ochratoxins / Q000633:toxicity*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002273:Carcinogens; D009793:Ochratoxins; D017382:Reactive Oxygen Species; C025589:ochratoxin A