title: Emodin induces embryonic toxicity in mouse blastocysts through apoptosis.
abstract: Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a major constituent of rhubarb, has a wide range of therapeutic applications. Previous studies have established that emodin inhibits cell proliferation and induces caspase 3-dependent apoptosis. However, its side-effects, particularly those on embryonic development, have not been well characterized as yet. In the current study, we examined the cytotoxic effects of emodin on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, and in vivo implantation by embryo transfer. Blastocysts treated with 25-75 μM emodin exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rate of blastocysts pretreated with emodin was lower than that of their control counterparts. Moreover, in vitro treatment with 25-75 μM emodin was associated with increased resorption of post-implantation embryos and decreased fetal weight. With the aid of an in vivo mouse model, we showed that consumption of drinking water containing emodin led to apoptosis and decreased cell proliferation, and inhibited early embryonic development to the blastocyst stage. Our findings support a degree of selective inhibition of retinoic acid receptors in blastocysts treated with emodin. In addition, emodin appears to induce injury in mouse blastocysts through intrinsic apoptotic signaling processes to impair sequent embryonic development. These results collectively indicate that emodin has the potential to induce embryonic cytotoxicity.
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li, Taiwan.
authors.forename: Mei-Hui
authors.initials: MH
authors.lastname: Chang
authors.forename: Fu-Jen
authors.initials: FJ
authors.lastname: Huang
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D004642:Emodin / Q000633:toxicity*; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008813:Mice, Inbred ICR; D008858:Microscopy, Phase-Contrast; D011247:Pregnancy; D012313:RNA / Q000737:chemistry / Q000235:genetics; D011897:Random Allocation; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018168:Receptors, Retinoic Acid; D012313:RNA; D004642:Emodin