Effect Of Different Levels Of Zinc Deficiency On The Development Of Heart In Rat Fetus And The Possible Mechanism

ObjectiveZinc is one of the essential trace elements, relating to many fuctions of the cells. Zinc deficiency can lead to organic dysfunction, dystrophy and fetal dysplasia. Gravidas require more zinc. Homeostasis of zinc is very important to normal pregnancy and fetal development during pregnancy. Congenital heart disease(CHD) is one of the most common diseases of human birth defects, which is seriously endangering infant,s health. This research established rat models of zinc deficiency through feeding them in diet with different content of zinc. It aims to study the effect of zinc deficiency on the development of heart in rat fetus and the relation between dose and effect; and the possible mechanism was also investigated. The object is to provide an experimental data for possible zinc supplement and prevention of CHD in clinic.Methods50 SD-healthy adult female rats were randomly divided into 5 groups, zinc acutely deficient group, zinc deficient group, zinc moderately deficient group, zinc marginally deficient group, normal zinc group, feeding in diet with different content of zinc. They were fed 25 days for depleting the zinc pool in the body, and mated with male rats. They were underwent feeding in diet with different content of zinc during pregnancy. All the pregnant rats were killed on the 19th day of pregnancy, the embryonic heart were sliced, and the heart defects observed. Blood level of zinc was determined by atomic absorption spectrophotometer and the serum AKP activity was determined by AKP kit. The expression of MT1 and ZNT1 mRNA in placenta was examined by RT-PCR. Results1. As compared with the normal zinc group, the serum AKP activity and blood zinc content in all the zinc deficient groups were significantly lowered (all P<0.05). Under the same conditions the changes of serum AKP activity were more obvious.2. In every group, it was found different extents of absorptive embryos, abnormal embryos and stillbirths. As compared with the normal zinc group, the incidences were significantly higher in the zinc acutely deficient group, zinc deficient group, and zinc moderately deficient group (all P<0.05).3. Embryo heart malformations were mainly hypoevolutial, atrial absence, ventricular septal defect, ventricular defect, and so on. As compared with the normal zinc group, embryo heart malformations were significantly higher in the zinc acutely deficient group, zinc deficient group, and zinc moderately deficient group (all P<0.01).4. The MT1 and ZNT1 mRNA levels in placenta were both significantly decreased in the zinc acutely deficient group, zinc deficient group and zinc moderately deficient group vs. normal zinc group. (all P<0.05).5. The MT1 and ZNT1 mRNA levels in placenta were both significantly decreased in the cardiac anomaly groups vs. the normal group (P<0.01).Conclusions1. The serum AKP activity and blood zinc content of rats reduced after feeding the rats with zinc-deficient diet of Flanagan formula. It indicated that the model is successful.2. Serum AKP activity is a sensitive indicator of zinc in body; combination with the blood level of zinc can be more accurately reflecting the level of zinc.3. Over moderately deficient zinc in the maternal body can increase heart malformations in embryos. The toxicity of zinc deficiency in embryos has a significant dose-effect relation. We must have a regard for preventing and curing over moderately deficiency of zinc. 4. Rats with over moderate zinc deficiency show increased heart malformations in embryos. The mechanism may include down-regulating the expression of MT1 mRNA in placenta and reducing the anti-oxidation in the body.5. As an output of zinc in cells, ZNT1 can influence the utilization of zinc in the body. Zinc deficiency in the body will reduce the expression of ZNT1, cause a reduced blood zinc content and decreased expression of MTs. All the above results can exacerbate the state of high oxidative stress in the body and increase heart malformations in embryos.6. It can't cause heart malformations in embryos unless zinc deficiency has influenced the expression of zinc-relating proteinums, such as MTs and ZNTs.