Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements.

Anna Bugge Janssen,Rosalind M John,Simon J Tunster,Alexander E P Heazell

doi:10.1186/s12881-016-0279-1

Anna Bugge Janssen, Rosalind M John + Show 2 more

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https://doi.org/10.1186/s12881-016-0279-1

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Abstract

BackgroundMaternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency. The maternally expressed imprinted gene PHLDA2 controls fetal growth, placental development and placental lactogen production in a mouse model. A number of studies have also demonstrated abnormally elevated placental PHLDA2 expression in human growth restricted pregnancies. This study examined whether PHLDA2 was aberrantly expressed in placentas of RFM pregnancies resulting in delivery of an FGR infant and explored a possible relationship between PHLDA2 expression and placental lactogen release from the human placenta.MethodsVillous trophoblast samples were obtained from a cohort of women reporting RFM (N = 109) and PHLDA2 gene expression analysed. hPL levels were assayed in the maternal serum (N = 74).ResultsPlacental PHLDA2 expression was significantly 2.3 fold higher in RFM pregnancies resulting in delivery of an infant with FGR (p < 0.01), with highest levels of PHLDA2 expression in the most severe cases. Placental PHLDA2 expression was associated with maternal serum hPL levels (r = −0.30, p = 0.008, n = 74) although this failed to reach statistical significance in multiple linear regression analysis controlling for birth weight (p = 0.07).ConclusionsThese results further highlight a role for placental PHLDA2 in poor perinatal outcomes, specifically FGR associated with RFM. Furthermore, this study suggests a potential relationship between placental PHLDA2 expression and hPL production by the placenta, an association that requires further investigation in a larger cohort.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0279-1) contains supplementary material, which is available to authorized users.

Highlights

Maternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency
Placental PLECKSTRIN HOMOLOGY-LIKE DOMAIN FAMILY A MEMBER 2 (PHLDA2) expression was significantly 2.3 fold higher in RFM pregnancies resulting in delivery of a growth restricted compared with a normal birth weight infant (Fig. 1a)
Placental PHLDA2 expression was significantly inversely associated with birth weight (r = −0.24, p = 0.01, n = 109), custom birth weight centiles (r = −0.25, p = 0.01, n = 109) and, in this study, placental weight (r = −0.39, p = 0.03, n = 31)

Summary

Introduction

Maternal perception of reduced fetal movements (RFM) is associated with increased risk of fetal growth restriction (FGR) and stillbirth, mediated by placental insufficiency. The maternally expressed imprinted gene PHLDA2 controls fetal growth, placental development and placental lactogen production in a mouse model. A number of studies have demonstrated abnormally elevated placental PHLDA2 expression in human growth restricted pregnancies. Imprinted genes are monoallelically expressed with expression depending on the parent of origin [14] These genes have well-established roles in controlling fetal growth and placental development, and are regulated by epigenetic marks that may respond to environmental stimuli [15,16,17].

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