Association Of Maternal Selenium Deficiency During Pregnancy With Fetal Growth Restriction And Its Mechanism

Background Selenium(Se)is one of essential trace elements for human body and it is an important component of glutathione peroxidase and thioredoxin reductase.It’s clear that selenium deficiency is linked with Keshan disease,diabetes and adverse pregnancy outcomes.However,association between maternal low selenium level during pregnancy and the risk for fetal growth restriction is still controversial.Objective The present study was to explore the association between maternal selenium deficiency during pregnancy and the risk for fetal growth restriction by birth cohort study and animal experiments and its mechanism.Methods The present study was composed by birth cohort study and animal experiments.For our cohort study,total 3133 mother-and-infant pairs were selected.Maternal serum Se concentration was detected by graphite furnace atomic absorption spectrometry.According to international references for maternal serum Se concentration,subjects were divided into Se deficiency(<45.0 μg/L),Se insufficiency(45.0-94.9 μg/L)and Se sufficiency(≥95.0 μg/L).The ratio of maternal characteristics and the rate of LBW and SGA were analyzed using the chi-square test.Maternal characteristics and serum Se level were analyzed using t test.ANOVA was used for multiple comparisons.The association of serum Se levels and the risk for LBW and SGA infants was analyzed using multiple logistic regression model.For our animal experiments,forty ICR female mice(three weeks)were randomly divided into control diet(CD)group and low-selenium diet(LSD)group,there were 20 mice in each group.Mice in CD group were feed control diet(the selenium content was 0.18 mg/kg)and mice in LSD groupwere feed low-selenium diet(the selenium content was 0.02 mg/kg).Females and males were mated after eight weeks and the pregnant mice were keeped the corresponding diet until sacrificed on gestational day(GD)18.Growth and development of fetuses were evaluated.Maternal sera,fetal sera and placentas were collected.Serum selenium concentration was detected by graphite furnace atomic absorption spectrometry.The m RNA expression of Sod1,Sod2,Cat in placenta was detected by q RT-PCR.The 3-NT expression in placenta was measured by immunohistochemistry and Western blotting.Results For our cohort study,results showed that the incidence of LBW newborns was 2.4% among subjects with Se insufficiency(OR: 1.98;95%CI: 1.10 to 3.58;P=0.024),and 4.7% among subjects with Se deficiency(OR: 3.92;95%CI: 2.03 to 7.56;P<0.001).After controlling the confounders,the OR for LBW newborns was 1.87(95%CI: 1.02 to 3.44;P=0.044)in subjects with Se insufficiency and 3.90(95%CI: 2.02 to 7.54;P<0.001)in subjects with Se deficiency.Moreover,the incidence of SGA newborns was 8.9% among subjects with Se insufficiency(OR: 1.49;95%CI: 1.11 to 2.01;P=0.009)and 14.6% among subjects with Se deficiency(OR: 2.63;95%CI: 1.83 to 3.77;P<0.001).Adjusted OR for SGA infants was 1.45(95%CI: 1.06 to 1.99;P=0.02)in subjects with Se insufficiency and 2.75(95%CI: 1.90 to 3.98;P<0.001)in subjects with Se deficiency.The results showed that there was a negative relation of maternal serum Se concentration in gestation and the risks for LBW and SGA.For our animal experiments,no significance difference was observed in food intake and weight gain between CD and LSD group(P>0.05).The serum selenium level of pregnant mice and fetal mice were detected.The results showed that pregnant and fetal serum selenium level in LSD group was significantly lower than that in CD group(P<0.05).The examinations on growth and development showed that the fetal weight in LSD group was significantly lower than that in CD group(P<0.05).Moreover,the results from immunostaining and Western blotting showed that 3-NTexpression in placenta from LSD group was significantly higher than that from CD group(P < 0.05).Conslusion Maternal Se deficiency during gestation elevates the risk for fetal growth restriction,maybe via triggering placental oxidative stress.