[Role of programmed cell death in mediating arsenic-induced rat embryo anomalies]

With a view to further investigating teratogenicity, embryotoxicity and teratogenic mechanism of arsenic on developing embryos, the relationship between apoptosis (programmed cell death, PCD) and arsenic-induced teratogenesis was studied during head-fold stage by using in situ 3'end-labeling of DNA and Nile blue sulfate (NBS) vital staining. Sprague-Dawley rats were intraperitoneally injected on gestation day 9.5 with doses of 0, 1, 4 and 8 mg/kg arsenic respectively, and killed at day 12, the results show that teratogenic incidence and mortality increased to 35.7% and 23.8% respectively, in apparent dose-effect relationship. In NBS staining experience, it was found that arsenic induced PCD in many areas, which related with abnormal development of brain, optic system, somite segmentation, limb bud and so on. In situ 3' end-labeling of DNA further supported above-mentioned results. The positive rate of apoptotic cell death was up to 55.6% (P < 0.05). This research suggested a positive correlation between abnormal PCD and teratogenesis. It may be seen that over-apoptosis is one of teratogenic mechanisms of arsenic. Moreover, our results show that necrosis plays some role in teratogenesis as well.