title: Carbendazim (MBC) disrupts oocyte spindle function and induces aneuploidy in hamsters exposed during fertilization (meiosis II).
abstract: Peri-fertilization exposure to Carbendazim (MBC; a microtubule poison) induces infertility and early pregnancy loss in hamsters. Presently, both in vivo and in vitro techniques were employed to characterize the effects of MBC on cellular aspects of fertilization in hamsters. Exposure to MBC during either in vivo or in vitro fertilization (IVF) induced identical morphological abnormalities in the maternal chromatin of zygotes and embryos. These abnormalities included either multiple second polar bodies (PB2), and/or multiple small female pronuclei (PN), or meiotic arrest. Multiple PB2, multiple female PN, multiple PB2 with multiple female PN, or meiotic arrest were exhibited by approximately 31%, 15%, 12%, and 2% of the in vivo zygotes; and 3%, 16%, 36%, and 20% of IVF zygotes, respectively. The effects of MBC persisted to day 2 of pregnancy as indicated by decreased (P < 0.05) embryo development to the two-cell stage and the presence of micronuclei in 6% of two-cell embryos from MBC-treated females. Immunofluorescence analysis of microtubules (MTs) confirmed that MBC disrupted spindle MTs during IVF. Numerical chromosome analysis revealed that a single dose of MBC administered during in vivo fertilization induced aneuploidy in the resulting pronuclear-stage zygotes. The present data point to two mechanisms by which peri-fertilization MBC exposure may induce early pregnancy loss: 1) arrested meiosis with no zygotic cleavage; or 2) induction of zygotic aneuploidy with subsequent developmental arrest.
authors.affiliation: Curriculum in Toxicology, University of North Carolina, Chapel Hill, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Zuelke
authors.forename: S D
authors.initials: SD
authors.lastname: Perreault
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D002219:Carbamates; D006224:Cricetinae; D005260:Female; D005306:Fertilization / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D005307:Fertilization in Vitro; D005659:Fungicides, Industrial / Q000633:toxicity*; D034882:Lamins; D008297:Male; D008540:Meiosis / Q000187:drug effects; D008647:Mesocricetus; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism; D009865:Oocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D011247:Pregnancy; D015053:Zygote / Q000187:drug effects
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D005659:Fungicides, Industrial; D034882:Lamins; D009687:Nuclear Proteins; C006698:carbendazim