Abundances of placental imprinted genes CDKN1C, PHLDA2 and IGF-2 are related to low birth weight and early catch-up growth in full-term infants born small for gestational age.

Yan Xing,Huiqiang Liu,Xiaomei Tong,Xinli Wang,Yunpu Cui,Umberto Simeoni

doi:10.1371/journal.pone.0218278

Yan Xing, Huiqiang Liu + Show 4 more

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https://doi.org/10.1371/journal.pone.0218278

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Journal: PloS one	Publication Date: Jun 13, 2019
Citations: 7	License type: CC BY 4.0

Affiliation: Peking University, Peking University Third Hospital

Abstract

Children born small for gestational age (SGA) generally have a catch-up growth and rapid weight gain in the first years of life, which is a high risk of insulin resistance and cardiovascular diseases later in life. It was reported that the level of imprinted genes IGF-2, CDKN1C and PHLDA2 regulates placental growth. We assessed these imprinted genes expression levels in placental tissue and their influences on catch-up growth of full-term SGA infants. The protein and mRNA levels of placental CDKN1C, PHLDA2 and IGF-2 were analyzed in 29 full-term SGA and 29 full-term infants born appropriate for gestational age (AGA) using quantitative RT-PCR and Western blot assay, respectively. Catch-up growth was indicated by increased standard deviation score (ΔSDS) of weight at 1, 3 and 6 months relative to birth weight (BW). Correlations between indicated variables were evaluated using Pearson correlation coefficient analysis. Compared to AGA infants, CDKN1C and PHLDA2 levels were significantly increased, whereas IGF-2 was significantly reduced in SGA infants. The value of ΔSDS was significantly higher in SGA than that in AGA infants. For SGA status, Pearson analysis shows i) a negative correlation of CDKN1C and PHLDA2 abundances with BW, and a positive correlation of IGF-2 with BW, ii) no correlation between the three imprinted gene abundances and placental weight (PW), and between PW and BW, iii) a positive correlation of PHLDA2 abundance with CDKN1C, and iv) a positive correlation of CDKN1C and PHLDA2 abundances with ΔSDS, and a negative correlation of IGF-2 with ΔSDS at 1, 3 and 6 months. Taken together, increased CDKN1C and PHLDA2 and reduced IGF-2 abundances in placental tissue were related to BW and early period catch-up growth in full-term SGA infants. Placental CDKN1C, PHLDA2 and IGF-2 level monitoring may be useful for predicting and preventing the development of SGA.

Highlights

Small for gestational age (SGA) is generally defined as low birth weight (BW) at 10th percentile or at less than -2 standard deviations from the mean [1,2]
Our findings show that increased Cyclin dependent kinase inhibitor 1C (CDKN1C) and pleckstrin homology-like domain family A member 2 (PHLDA2) and reduced Insulin-like growth factors (IGFs)-2 abundances in placental tissue were related to BW reduction and early period catch-up growth in the SGA infants
There were no significant differences in the gestational age, and mother’s age, weight, height and delivery way as well as father’s age, weight and height between the SGA and the appropriate for gestational age (AGA) infants

Summary

Introduction

Small for gestational age (SGA) is generally defined as low birth weight (BW) at 10th percentile or at less than -2 standard deviations from the mean [1,2]. Alterations of the expressions of specific imprinted genes are related to appropriate fetal and placental growth [4]. Insulin-like growth factors (IGFs) have a major role in promoting embryonic and fetal growth as well as growth during infancy and childhood. In accordance with this role, abnormalities of IGFs level were found in the SGA children. It was reported that mean serum levels of IGF-1 and IGF-binding protein 3 in the SGA infants at birth were significantly lower than those in the appropriate for gestational age (AGA) births [7,8]. The mRNA levels of IGF-2 in chorionic villus in the SGA neonates were significantly lower than those in the AGA neonates. A persistent downregulation of the IGF-1 levels was reported in the SGA children [17], whereas upregulated IGF-1 level was found in the SGA children with catch-up growth [7,8]

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