Embryotoxicity of arsenic acid: light and electron microscopy of its effect on neurulation-stage rat embryo

To clarify the light and electron microscopic changes accompanying embryonic death from a lethal dose of arsenic acid, MP 1 pregnant rats were injected i.p. with 30 mg/kg arsenic acid at 1:30 p.m. on day 9 of gestation (the neurulation stage). At 4 hours after treatment, some cell necrosis occurred in the neuroectoderm and the mesoderm of the embryo. At six hours later, cell necrosis increased in the neuroectoderm and the mesoderm, whereas those in the surface ectoderm and the endoderm were very few. In the embryo 12 hours after treatment, abnormal mitotic cells exhibiting vesiculation of the endoplasmic reticula, and abnormal interphase cells characterized by the ring-shaped nucleoli in the nucleus and the enlargement of cisternae of the endoplasmic reticula and the nuclear envelope, were observed in the neuroectoderm and the mesoderm. Debris from cell necrosis and the said abnormal mitotic and interphase cells were ejected from the neuroectoderm into the amniotic coele. In the embryo 24 hours later, neurulation was stopped and the V-shaped neural fold remained. The somite formation was retarded. The surviving cells in the embryo sometimes contained phagocytic vesicles in the cytoplasm, but no other anomalies were encountered. It was considered that a variety of metabolic reactions may be disturbed by arsenic acid, resulting in numerous cell necrosis and abnormal mitotic and interphase cells in the neuroectoderm and the mesoderm of the rat embryo.