title: Placental PHLDA2 expression is increased in cases of fetal growth restriction following reduced fetal movements.
abstract: BACKGROUND
  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 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.
  
  
  METHODS
  Villous 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).
  
  
  RESULTS
  Placental 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).
  
  
  CONCLUSIONS
  These 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.
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, UK. JensenAB1@cardiff.ac.uk.
authors.forename: Anna Bugge
authors.initials: AB
authors.lastname: Janssen
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, UK. tunstersj@Cardiff.ac.uk.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Tunster
authors.affiliation: Maternal and Fetal Health Research Centre, University of Manchester, Manchester, UK. alexander.heazell@manchester.ac.uk.
authors.forename: Alexander E P
authors.initials: AE
authors.lastname: Heazell
authors.affiliation: Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, CF10 3AX, UK. JohnRM@cardiff.ac.uk.
authors.forename: Rosalind M
authors.initials: RM
authors.lastname: John
mesh_terms: D015331:Cohort Studies; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000235:genetics*; D005324:Fetal Movement; D005786:Gene Expression Regulation; D006801:Humans; D007231:Infant, Newborn; D016014:Linear Models; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D010928:Placental Lactogen / Q000097:blood; D011247:Pregnancy; D011256:Pregnancy Outcome; D050497:Stillbirth
chemical_list: D009687:Nuclear Proteins; C109277:TSSC3 protein; D010928:Placental Lactogen