Changes in the mouse neuroepithelium associated with cadmium-induced neural tube defects

Abstract

The aim of this study was to investigate the teratogenic action of cadmium (Cd) on the developing mouse CNS. Pregnant mice were injected with 4 mg/kg CdCl2 on day 7, 8, 9, or 10 of gestation. These animals and saline injected controls were sacrificed either on the day before birth or at various times up to 48 hours after injection and the embryos examined grossly and histologically. Exencephaly occurred after Cd treatment on day 7 or 8 and its development was examined in day 8 embryos. Eight hours after Cd injection many cells of the closing neural plate contained dense-staining inclusions, thought to be autophagic vacuoles. After 24 hours this damage had almost disappeared, but the anterior neural folds, although looking histologically normal, were more open than in controls. Forty-eight hours after injection it was apparent that this part of the neural tube was not going to close and would result in exencephaly. Cd exposure on day 9 or 10 did not cause gross CNS defects such as exencephaly. On both days, twelve hours after Cd injection, similar dark-staining inclusions were seen in many cells throughout the CNS. After twenty-four hours there were variable amounts of cell death, resulting in some embryos in breakdown of parts of the wall of the neural tube. Forty-eight hours after treatment all inclusions and cellular debris had disappeared, indicating repair had taken place, but in some embryos, treated on day 9, severe lasting damage was seen as dorsal openings in the previously closed neural tube.