Associations between Placental Insulin-Like Growth Factor-1 Gene Expression, DNA Methylation and Intrauterine Growth Restriction

Xiaojuan Li,Zhuo Wang,Qiaomiao Zhou,Xueli Wu,Hongtao Zhou,Caihong Jia,Shengmiao Fu,Baifeng Yu,Xinping Chen,Jiye Zhang,Guohui Yi

doi:10.4236/health.2020.123022

Abstract

Intrauterine growth restriction (IUGR) is a common fetal development disorder which has great impact on neonatal health. Insulin-like growth factor-1 (IGF1) has an important role in regulating fetal growth. Whether IGF1 DNA methylation was associated with IUGR has not been studied. Placenta samples from IUGR (n = 27) and normal delivery (n = 29) were collected whereas basic information of mothers and infants were also collected. RT-PCR was performed to examine IGF1 transcriptions and bisulfite sequencing PCR was used for DNA methylation analysis. Gene expression analysis found IUGR had significantly lower IGF1 transcription compared to control group (IUGR: 0.330 ± 0.351; control group: 1.001 ± 0.800, t = 3.995, P IGF1 were all highly methylated and there is no difference on DNA methylation rate between IUGR and control group (IUGR: 75%; control group: 81%; P = 0.09). Interestingly, in both IUGR and control groups, male fetus had significantly higher methylation rate than female fetus (IUGR: male: 87%; female: 74%, P = 0.016; control: male: 82%; female: 69%, P = 0.012). There was no correlation between IGF1gene expression and DNA methylation rate (r = 0.095, P = 0.063). Intrauterine fetal growth restriction placenta had significantly lower IGF1gene expression; however, IGF1 DNA methylation level was similar. A potential fetus gender difference was also found in IGF1 DNA methylation rate.

Highlights

Fetal growth restriction, called intrauterine growth restriction (IUGR), is a common fetal development disorder which has great impact on neonatal health
Children with Intrauterine growth restriction (IUGR) are born smaller than gestational age (SGA), the term SGA will be used exclusively to describe newborns whose birth weight is less than the 10th percentile for gestational age [4]
This study demonstrated that the placenta from IUGR fetus had significantly lower Insulin-like growth factor-1 (IGF1) transcription levels

Summary

Introduction

Called intrauterine growth restriction (IUGR), is a common fetal development disorder which has great impact on neonatal health. Previous studies have shown that a compromised intrauterine environment increased the risk of IUGR, Preeclampsia (PE), Intrauterine virus infection and malnutrition all cause IUGR in premature infants, causes the fetus to be born SGA These children have inadequate intrauterine nutrition reserves, there were more complications after birth, prone to feeding intolerance, infection and other causes, this causes slow growth after birth, and the risk of diseases during adulthood and led to permanent change of physiology and metabolism through modulating developmental programming [6]. Researchers have pointed out that IUGR neonates had greater risk of intellectual and physical growth retardation, insulin resistance, obesity, and diabetes later in childhood and adulthood [7] [8] [9] It was indicated by a previous study that the insulin-like growth factor 1 (IGF1) in the umbilical cord was responsible for the growth, nutrition transportation of fetus and the placenta [10]. Previous studies demonstrated that IGF1 axis mutation led to severe fetal growth retardation [16] [17]

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