Effect Of Iron Deficiency In Pregnant Rats On Hypothalamus-pituitary And IGF-1 Axis Of Offspring

Objective:The hypothalamus-pituitary and IGF-1 axis is an important way to promote growth.This paper aims to explore how iron deficiency in pregnant rats affects their hypothalamus-pituitary and IGF-1 axis of offspring and its mechanism.Methods: 1.Establishing rats model of perinatal iron deficiency: four-week-old healthy female Wistar rats were randomly divided into experimental group(n=18)and control group(n=18).The rats of the experimental group were fed with low iron diet,while the control group were fed with normal diet.After four weeks,according to the 2: 1 ratio,the rats were mated with healthy adult male rats.Hematological parameters of the rats’ eye vein blood were detected,including hemoglobin(Hb),haematocrit(HCT),mean corpuscular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red blood cell distribution width(RDW).Pregnant rats were randomly drawn from each group to measure the iron of bone marrow.2.The survival rate and weight of newborn rat offspring were observed.The serum GH of rat offspring was detected by ELISA.3.The hypothalamus,pituitary and adrenal gland were cultured in vitro and identified by cell immunochemical method.4.The m RNA expressions of growth hormone-releasing hormone(GHRH),somatostatin(SST),erythropoietin(EPO),erythropoietin receptor(EPOR)and hypoxia-inducible factor-1(HIF-1)in hypothalamus;growth hormone(GH),EPO and EPOR in pituitary;EPOR in adrenal gland;insulin-like growth factor-1(IGF-1),EPO,EPOR and HIF-1 in liver of newborn rats were assessed by quantitative real-time PCR.5.The expression of EPOR protein in the liver of newborn rats were detected by Western-blot.Results: 1.Rats model of perinatal iron deficiency were established successfully.The levels of Hb,HCT,MCV,MCH and MCHC in the experimental group were significantly lower(P<0.01)than those of the control group,while RDW increased remarkably(P<0.01).In the experimental group,iron in pregnant rats’ bone marrow decreased significantly more than that in the control group.2.Pregnant rats had dystocia at the end of gestation in the experimental group.Compared with the control group,the survival rate and weight of newborn offspring were decreased significantly(P<0.01).3.Compared with the control group,the expression of GH m RNA and IGF-1 m RNA of offspring decreased significantly(P<0.05)in the experimental group.4.In the experimental group,the expression of GHRH m RNA in the hypothalamus of the newborn offspring was decreased(P>0.05)more than that in the control group,and the expression of SST m RNA was up-regulated(P>0.05).5.Compared with the control group,the expression of EPO m RNA in the liver was increased significantly(P<0.05)in the experimental group and was decreased significantly(P<0.01).The expression of EPO m RNA in the hypothalamus had no difference between experimental group and control group(P>0.05).6.There was no significant difference of HIF-1 m RNA and EPOR m RNA in the hypothalamus,pituitary and liver of the newborn offspring between the iron deficiency group and conrol group(P>0.05).Compared with the control group,the expression of EPOR protein in the liver had no significant difference in the experimental group(P>0.05).Conclusion: 1.Iron deficiency during pregnancy leads to low birth weight through down-regulating the expression of GH m RNA and IGF-1 m RNA of offspring.2.Iron deficiency during pregnancy leads to increased the secretion of EPO to alleviate anemia in offsprings’ liver.However,the expression of EPOR in the hypothalamus,pituitary,adrenal and liver did not increased,which may be related to chronic hypoxia caused by anemia.