Effects Of Dexamethasone On Iron Metabolism In Pergnant And Fetal Rats

Iron is one of the essential trace elements for the growth and development of animals.It is especially important for pregnancy and fetal development.Iron deficiency during pregnancy leads to harmful effects on the fetus,such as fetal growth and development disorders,inhibiting fetal nerve activity,resulting in long-term neurological dysfunction,and even increasing the risk of illness in adulthood.In this experiment,dexamethasone was used to explore the effects of glucocorticoids on iron metabolism and placental iron transport in rats during pregnancy stress.1.Effects of dexamethasone on body weight,blood biochemical parameters and iron metabolism-related indexes in pregnant ratsIn experiment,24 SD pregnant rats were randomly divided into two groups,12 in the control group and 12 in the dexamethasone drinking group.The treatment was started on the 13th day of pregnancy.The pregnant rats were given normal drinking water in the control group,whereas the other rats were given water containing dexamethasone at the dose of 0.2 mg/kg/day.The body weight,average daily feed intake and average daily iron intake were recorded and calculated during the experiment.After 7-day treatment,pregnant rats were slaughtered to remove liver,spleen,kindy and heart,and collect plasma sample.The tissue samples were weighed to calculate organ index.The liver and plasma samples were treated to detect biochemical parameters,antioxidant index and iron metabolism-related index.The results showed that dexamethasone significantly reduced the final weight of pregnant rats(P<0.05),impaired organ(liver,spleen and kindy)development,decreased the level of plasma ALP,SOD and hepatic SOD,GSH-Px(P<0.05),enhanced the content of plasma CHOL,TG,HDL-C,GLU,AST,ALT,LDH,TP,ALB,TBIL,MDA,iron metabolism-related index(plasma iron,Tf-Fe3+,TIBC and TS)in pregnant rats.2.Effects of dexamethasone on intestinal and hepatic iron metabolism in pregnant ratsTo investigate the dexamethasone on iron metabolism of duodenum and liver in pregnant rats,qPCR and western blot were used to detect the expression of genes and proteins related to iron absorption,transport,storage and release.Western blot results showed that dexamethasone significantly reduced the expression of duodenal iron-releasing protein(FPN),iron storage protein(FTH and FTL)(P<0.05).In addition,dexamethasone greatly up-regulated hepatic iron-uptake proteins TfR1,TfR2 and ZIP14 expression and down-regulated hepatic iron-storage proteins FTL and FTH expression in pregnant rats.3.Effects of dexamethasone on iron transport function in placenta and BeWo cellsThe placenta acts as a nutrient transporter that connects the mother to the embryo,and all the iron is transferred to fetus for fetal development.At the end of stress,the total weight of the fetus,liver weight,placental weight,placental diameter and thickness were recorded.The results showed that dexamethasone significantly reduced placental weight,placental diameter and fetal iron content(P<0.05).Western blot results showed that dexamethasone markedly down-regulated iron-uptake protein TFR1 expression,but increased iron-storage protein FTH and FTL expression(P<0.05).Dexamethasone impaired the expression of hepatic iron-uptake protein TFR1 and ZIP 14,iron-export protein FPN,and IRP1,but enhanced iron-storage protein FTL in fetal rats(P<0.05).In BeWo cell models,dexamethasone also decreased TFR1 expression at the mRNA and protein level(P<0.05),and down-regulated IRP1 protein expression(P<0.05).In addition,dexamethasone greatly enhanced phosphorylated GR(p-GR)protein expression(P<0.05),and its antagonist RU486 supplementation could inhibit the phosphorylation of GR and also alleviated the down-regulation of TFR1(P<0.05).In summary,dexamethasone could reduce final weight,impaired organ(liver,spleen and kindy)development and affect antioxidant index,glucose,lipid metabolism and iron metabolism in pregnant rats.Dexamethasone could disrupt iron absorption and hepatic iron metabolism by decreasing duodenal FPN and hepatic iron-storage protein(FTH and FTL)expression,and increasing hepatic iron-uptake proteins(TFR1 and TFR2)expression in pregnant rats.Maternal dexamethasone impaired placental development and iron content of fetal rats by down-regulating iron-transport protein TFR1 expression.