Abstract

A linkage of dichorionic (DC) twin pregnancies with selective intrauterine growth restriction (IUGR) to alterations in placental gene expression is unclear. The aim of the study was to identify placental genes related to hypoxia, adipogenesis and human growth which may contribute to IUGR development. The study group (IUGR/AGA) comprised dichorionic (DC) twin pregnancies, where the weight of the twins differed by > 15%; in addition, one twin was small for gestational age (< 10th percentile-SGA) (IUGR) while the other was appropriate for gestational age (> 10th percentile-AGA). In the control group (AGA/AGA), both fetuses were AGA and their weights differed by < 15%. In the first step (selection), placental expression of 260 genes was analysed by commercial PCR profiler array or qPCR primer assay between six pairs of IUGR/AGA twins. In the second stage (verification), the expression of 20 genes with fold change (FC) > 1.5 selected from the first stage was investigated for 75 DC pregnancies: 23 IUGR/AGA vs. 52 AGA/AGA. The expression of Angiopoetin 2, Leptin and Kruppel-like factor 4 was significantly higher, and Glis Family Zinc Finger 3 was lower, in placentas of SGA fetuses (FC = 3.3; 4.4; 1.6; and − 1.8, respectively; p < 0.05). The dysregulation of gene expression related to angiogenesis and growth factors in placentas of twins born from IUGR/AGA pregnancies suggest that these alternations might represent biological fetal adaptation to the uteral condition. Moreover, DC twin pregnancies may be a good model to identify the differences in placental gene expression between SGA and AGA fetuses.

Highlights

  • Intrauterine growth restriction (IUGR) is an important cause of fetal and neonatal morbidity and mortality

  • This leads to a restriction in oxygen and nutrient supply through the placenta to the fetus resulting in placental hypoxia and its apoptosis (Erel et al 2001)

  • The present study found significantly increased expression of ANGPT2, Kruppel-like factor 4 (KLF4), and LEP but lower expression of GLIS3 gene in the placentas of small for gestational age (SGA) twins compared to their AGA co-twins

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Summary

Introduction

Intrauterine growth restriction (IUGR) is an important cause of fetal and neonatal morbidity and mortality. As it is usually defined for singleton pregnancies as the rate of fetal growth below the 10th percentile of a population-specific birth weight for gestational age, the terms IUGRand small for gestational age (SGA) are often used interchangeably (Sharma et al 2016). Various criteria exist for IUGR diagnosis twin pregnancies; the following two are used most frequently: (1) either twin with a birth weight < 10th percentile for gestational age, (2) the presence of a 10–30% difference in birthweight between co-twins (Breathnach and Malone 2012; Moore and O’Brien 2006; Ropacka-Lesiak et al 2012; Yinon et al 2005).

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