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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.
Insights
Cadmium exposure during early mouse pregnancy can cause severe central nervous system (CNS) defects like exencephaly. Later exposure may lead to lasting neural tube damage, even after initial repair.
Area of Science:
- Developmental toxicology
- Neuroscience
- Teratology
Background:
- Cadmium (Cd) is a toxic heavy metal with known adverse effects on development.
- Understanding the specific timing and mechanisms of Cd-induced teratogenicity is crucial for risk assessment.
Purpose of the Study:
- To investigate the teratogenic effects of cadmium chloride (CdCl2) on the developing central nervous system (CNS) of mouse embryos.
- To determine the critical developmental windows for Cd-induced CNS malformations.
Main Methods:
- Pregnant mice were administered CdCl2 (4 mg/kg) on gestation days 7, 8, 9, or 10.
- Embryos were examined grossly and histologically at various time points post-injection.
- Control groups received saline injections.
Main Results:
- Cd exposure on days 7 or 8 led to exencephaly, characterized by open neural folds and failure of neural tube closure.
- Early Cd exposure induced cellular damage (autophagic vacuoles) in the closing neural plate.
- Cd exposure on days 9 or 10 caused transient cellular damage and cell death within the CNS, with some embryos showing lasting dorsal neural tube defects.
Conclusions:
- The timing of cadmium exposure is critical for the type and severity of CNS teratogenesis in mice.
- Early gestation (days 7-8) is a sensitive period for Cd-induced exencephaly.
- Later gestation (days 9-10) exposure can result in significant, persistent neural tube damage despite apparent cellular repair.