title: Oxidative stresses-mediated apoptotic effects of ginsenoside Rb1 on pre- and post-implantation mouse embryos in vitro and in vivo.
abstract: Ginsenoside Rb1, the major saponin component of ginseng root, has a wide range of therapeutic application. Previous studies have established that ginsenoside Rb1 inhibits the cell cycle and induces apoptosis. However, its side-effects, particularly those on embryonic development, have not been well characterized to date. In the current study, we examined whether ginsenoside Rb1 exerts a cytotoxic effect on mouse embryos at the blastocyst stage, and affects subsequent embryonic development in vitro and in vivo. Blastocysts treated with 25-100 μg mL-1ginsenoside Rb1 exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rate of blastocysts pretreated with ginsenoside Rb1 was lower than that of their control counterparts. Moreover, in vitro treatment with 25-100 μg mL-1ginsenoside Rb1 was associated with increased resorption of post-implantation embryos and decreased fetal weight. In an in vivo model, intravenous injection with ginsenoside Rb1 (1, 3, 5 mg kg-1body weight/day) for 4 days resulted in apoptosis of blastocyst stage embryos and early embryonic developmental injury. In addition, ginsenoside Rb1 appeared to induce injury in mouse blastocysts through oxidative stresses-triggered intrinsic apoptotic signaling processes to impair sequent embryonic development. The collective results strongly indicate that ginsenoside Rb1 induces apoptosis and retards early pre- and post-implantation development of mouse embryos, both in vitro and in vivo. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1990-2003, 2017.
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li District, Taoyuan City, 32023, Taiwan.
authors.forename: Bugi
authors.initials: B
authors.lastname: Ratno Budiarto
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li District, Taoyuan City, 32023, Taiwan.|Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, 404, Taiwan.
authors.forename: Wen-Hsiung
authors.initials: WH
authors.lastname: Chan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001755:Blastocyst / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D036145:Ginsenosides / Q000633:toxicity*; D008297:Male; D008813:Mice, Inbred ICR; D018384:Oxidative Stress / Q000187:drug effects*; D011247:Pregnancy; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D036145:Ginsenosides; C442759:ginsenoside Rb1
keywords: apoptosis; blastocyst; embryonic development; ginsenoside Rb1; oxidative stress