| Objective:To observe whether cadmium can penetrate the placental barrier of female Sprague-Dawley rats, to study the influence of cadmium on the embryonic development, and to provide data for further mechanism research on cadmium developmental toxicityMethods:40female SPF Sprague-Dawley rats were randomly and equally divided into2groups with20rats each, a control group and a112Cd2+treated group. The control group was given subcutaneously with deionized water, and the112Cd2+treated group hypodermically with40μg112Cd2+/kg bodyweight daily continuously for45～58days. On the24th day of the exposure, all female rats began to mate with healthy male SD rats. Next morning, the signs of pregnancy, including vaginal plug or sperm in the females, were examined. On the20th day of pregnancy, the pregnant rats were anesthetized with ether and sacrificed. Main organs of the dams and the foetuses were collected and examined as follow.(1) Cadmium distribution in the dams:Blood samples of the maternal and the umbilical cord were measured for the cadmium contents with atomic absorption spectrometer (AAS). Inductively coupled plasma mass spectrometry (ICP-MS) was employed to analyze cadmium levels in brain, heart, liver, kidney and placenta. The blood biochemistry, blood estradiol and microalbumininurine, urine retinol combined with protein and urine creatinine were determined. The rates of embryonic absorptions, foetal deaths and viable foetuses were analyzed.(2) The influence of cadmium on embryonic development:Foetal growth indexes were analyzed. Cord blood samples were measured for the cadmium contents with AAS, to observe whether the cadmium could penetrate the placental barrier. ICP-MS was employed to analyze the levels and distributions of cadmium in brain, heart, liver and kidney of the foetuses. Effect of cadmium on bone formation of the foetuses was also studied whether low-dose cadmium could cause fetal skeletal deformities. The foetuses were observed under a dissecting microscope after a series of fixing, transparent, staining, decolorization.(3) Impact of low dose cadmium on pathological changes of the maternal and fetal organs. Brain, heart, liver, kidney and placenta of the dams and foetuses were fixed, dehydrated, embedded, sectioned and stained. Under the ordinary optical microscope the morphological changes in the above organs were checked, in order to study whether pathological changes in the maternal and fetal organs were caused by low-dose cadmium.Results:(1) The distribution of low-dose cadmium in the dams:①the distribution and load of cadmium in the body:compared with those of the control group, cadmium contents in brain, heart, liver, kidney and placenta of the112Cd2+treated group, the differences were statistically significant (P<0.01). Similarly, cadmium contents in maternal blood at the24th day of injection and the20th day of pregnancy in the112Cd2+treated group were statistically higher (P<0.01). There was a significant difference of the urine cadmium contents between2groups on the20th day of pregnancy (P<0.05).②Liver and renal function indexes of the female rats:The difference of the contents of urine retinol binding protein at the24th day of injection and the20th day of pregnancy between2groups was significant (P<0.01), while the difference of the microalbumininurine content between the groups at the same period was not significant (P>0.05). At the20th day of pregnancy, the difference existed only in the indexes of AST and CREA between the2groups (P<0.01).③Compared with those of the control, the increased embryonic absorption rates, the decreased viable foetus rate and the decreased estradiol level in the112Cd2+treated group were significantly observed (P<0.01).(2)The influence of cadmium on embryonic development:①Compared with those of the control group, the weight of placental and foetuses significantly decreased in the112Cd2+treated group (P<0.01).②Compared with those of the control group, cadmium concentrations in the brain, heart and liver of the foetuses were also significantly higher in the112Cd2+treated group (P<0.01) but the concentration of fetal kidney (P>0.05).③Skeleton malformation rate of the foetuses in the112Cd2+treated group was significantly higher than that of the control group. The main manifestations were the higher rates of dysostosis of sternum or metacarpal, and higher rate of unossification sternum in the cadmium exposure group.(3)Impact of cadmium on pathological changes of the maternal and fetal organs:Only the rates of pathological changes in maternal liver and kidney were significantly higher than those of the control group, but not in the placenta and fetal organs. The pathological changes were mild and diffuse tubular follicular epithelial vacuolation and liver cell edema and swelling, etc.Conclusion:Stable isotopes of cadmium (112Cd2+) at the dose of40μg/kg body weight was subcutaneously injected in female SPF SD rats, daily for the four estrous cycle of female rats (24days) and pregnancy (20days). Continuous cadmium can increase the mortality of rat embryos; reduce the rate of viable foetus and the weight of placental and foetuses. Low-dose cadmium can penetrate the placental barrier of the rats and distribute to the brain, heart, liver, kidneys and other organs of the foetuses. Cadmium can cause skeletal deformities and hinder the formation of bone in feotuses of rats, the main manifestations were mainly the dysostosis of sternum or metacarpal, and unossification sternum. The distribution of cadmium in the organs of the dams was observed to be liver, kidney, brain, placenta, heart in descending order. Decreased estradiol level in the112Cd2+treated group was seen. Liver, kidney functions were affected and pathological changes in liver and kidney were elicited. This test simulated the one-generation breeding experiment in rats, setting up continuous and chronic exposure model, which was consistent with the fact of human contact. |
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