title: Hazardous apoptotic effects of 2-bromopropane on maturation of mouse oocytes, fertilization, and fetal development.
abstract: 2-Bromopropane (2-BP) is used as an alternative to ozone-depleting cleaning solvents. Previously, we reported that 2-BP has cytotoxic effects on mouse blastocysts and is associated with defects in subsequent development. Here, we further investigate the effects of 2-BP on oocyte maturation and subsequent pre- and post-implantation development, both in vitro and in vivo. Notably, 2-BP induced a significant reduction in the rates of oocyte maturation, fertilization, and in vitro embryonic development. Treatment of oocytes with 2-BP during in vitro maturation (IVM) resulted in increased resorption of postimplantation embryos and decreased fetal weights. Experiments with a mouse model disclosed that consumption of drinking water containing 20 μM 2-BP led to decreased oocyte maturation in vivo and fertilization in vitro, as well as impairment of early embryonic development. Interestingly, pretreatment with a caspase-3-specific inhibitor effectively prevented 2-BP-triggered hazardous effects, suggesting that embryonic impairment by 2-BP occurs via a caspase-dependent apoptotic process. A study using embryonic stem cells as the assay model conclusively demonstrated that 2-BP induces cell death processes through apoptosis and not necrosis, and inhibits early embryo development in mouse embryonic stem cells. These results collectively confirm the hazardous effects of 2-BP on embryos derived from pretreated oocytes.
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan; E-Mail: whchan@cycu.edu.tw ; Tel.: +886-3-265-3515;
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001755:Blastocyst / Q000187:drug effects*; D061945:Caspase Inhibitors / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000187:drug effects; D005260:Female; D005306:Fertilization / Q000187:drug effects; D005328:Fetal Viability / Q000187:drug effects; D020567:Fetal Weight / Q000187:drug effects; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D011247:Pregnancy; D012997:Solvents / Q000633:toxicity*
chemical_list: D061945:Caspase Inhibitors; D006842:Hydrocarbons, Brominated; D012997:Solvents; C103736:2-bromopropane