Developmental and dysmorphogenic effects of glufosinate ammonium on mouse embryos in culture.
The effects of glufosinate ammonium on embryonic development in mice were examined using whole embryo and micromass cultures of midbrain and limb bud cells. In day 8 embryos cultured for 48 hr, glufosinate caused significant overall embryonic growth retardation and increased embryolethality to 37.5% at 10 micrograms/ml (5.0 x 10(-5) M). All embryos in the treated groups exhibited specific morphological defects including hypoplasia of the prosencephalon (forebrain) (100%) and visceral arches (100%). In day 10 embryos cultured for 24 hr, glufosinate significantly reduced the crown-rump length and the number of somite pairs, and produced a high incidence of morphological defects (84.6%) at 10 micrograms/ml. These embryos were characterized by blister in the lateral head (100%), hypoplasia of prosencephalon (57.1%), and cleft lips (42.9%) at 20 micrograms/ml (10.0 x 10(-5) M). Histological examination of the treated embryos showed numerous cell death (pyknotic debris) present throughout the neuroepithelium in the brain vesicle and neural tube, but did not involve the underlying mesenchyme. In micromass culture, glufosinate inhibited the differentiation of midbrain cells in day 12 embryos with 50% inhibition occurring at 0.55 microgram/ml (2.8 x 10(-6) M). The ratios of 50% inhibition concentration for cell proliferation to cell differentiation in limb bud cells were 0.76 and 1.52 in day 11 and 12 embryos, respectively. These findings indicate that glufosinate ammonium is embryotoxic in vitro. In addition to causing growth retardation, glufosinate specifically affected the neuroepithelium of the brain vesicle and neural tube, leading to neuroepithelial cell death.
Watanabe
T
T
Department of Hygiene and Preventive Medicine, Yamagata University School of Medicine, Japan. twatanab@med.id.yamagata-u.ac.jp
Iwase
T
T
D000014:Abnormalities, Drug-Induced / Q000209:etiology*; D000613:Aminobutyrates / Q000633:toxicity*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D005260:Female; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011247:Pregnancy; D013723:Teratogens / Q000633:toxicity*
D000613:Aminobutyrates; D004791:Enzyme Inhibitors; D006540:Herbicides; D013723:Teratogens; C003121:phosphinothricin