title: Dihydrolipoic acid induces cytotoxicity in mouse blastocysts through apoptosis processes.
abstract: α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 μM DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 μM DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 μM DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 μM do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 μM DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity.
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Houng
authors.affiliation: Department of Biomedical Engineering and Center for Nano Bioengineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan.
authors.forename: Cheng-An J
authors.initials: CJ
authors.lastname: Lin
authors.affiliation: Department of Physics, Chung Yuan Christian University, Chung Li 32023, Taiwan.
authors.forename: Ji-Lin
authors.initials: JL
authors.lastname: Shen
authors.affiliation: Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City 252, Taiwan.
authors.forename: Hung-I
authors.initials: HI
authors.lastname: Yeh
authors.affiliation: Departments of Internal Medicine and Medical Research, Mackay Memorial Hospital, Mackay Medical College, New Taipei City 252, Taiwan.
authors.forename: Hsueh-Hsiao
authors.initials: HH
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering and Center for Nano Bioengineering, Chung Yuan Christian University, Chung-Li 32023, Taiwan.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Chang
authors.affiliation: Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, 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*; D049109:Cell Proliferation / Q000187:drug effects; D010064:Embryo Implantation / Q000187:drug effects; D004624:Embryo Transfer; D047108:Embryonic Development / Q000187:drug effects*; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D011247:Pregnancy; D008063:Thioctic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D008063:Thioctic Acid; C015144:dihydrolipoic acid