title: Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3.
abstract: Maternal prenatal stress during pregnancy is associated with fetal growth restriction and adverse neurodevelopmental outcomes, which may be mediated by impaired placental function. Imprinted genes control fetal growth, placental development, adult behaviour (including maternal behaviour) and placental lactogen production. This study examined whether maternal prenatal depression was associated with aberrant placental expression of the imprinted genes paternally expressed gene 3 (PEG3), paternally expressed gene 10 (PEG10), pleckstrin homology-like domain family a member 2 (PHLDA2) and cyclin-dependent kinase inhibitor 1C (CDKN1C), and resulting impaired placental human placental lactogen (hPL) expression.
  
  
  
  A diagnosis of depression during pregnancy was recorded from Manchester cohort participants' medical notes (n = 75). Queen Charlotte's (n = 40) and My Baby and Me study (MBAM) (n = 81) cohort participants completed the Edinburgh Postnatal Depression Scale self-rating psychometric questionnaire. Villous trophoblast tissue samples were analysed for gene expression.
  
  
  
  In a pilot study, diagnosed depression during pregnancy was associated with a significant reduction in placental PEG3 expression (41%, p = 0.02). In two further independent cohorts, the Queen Charlotte's and MBAM cohorts, placental PEG3 expression was also inversely associated with maternal depression scores, an association that was significant in male but not female placentas. Finally, hPL expression was significantly decreased in women with clinically diagnosed depression (44%, p < 0.05) and in those with high depression scores (31% and 21%, respectively).
  
  
  
  This study provides the first evidence that maternal prenatal depression is associated with changes in the placental expression of PEG3, co-incident with decreased expression of hPL. This aberrant placental gene expression could provide a possible mechanistic explanation for the co-occurrence of maternal depression, fetal growth restriction, impaired maternal behaviour and poorer offspring outcomes.
authors: Cardiff School of Biosciences,Cardiff University,Cardiff CF10 3AX,UK.
authors: A B
authors: AB
authors: Janssen
authors: Centre for Mental Health,Imperial College,Hammersmith Campus,London W12 0NN,UK.
authors: L E
authors: LE
authors: Capron
authors: Douglas Mental Health University Institute,6875 La Salle Boulevard,Verdun,Quebec H4H 1R3,Canada.
authors: K
authors: K
authors: O'Donnell
authors: Cardiff School of Biosciences,Cardiff University,Cardiff CF10 3AX,UK.
authors: S J
authors: SJ
authors: Tunster
authors: Centre for Mental Health,Imperial College,Hammersmith Campus,London W12 0NN,UK.
authors: P G
authors: PG
authors: Ramchandani
authors: Maternal and Fetal Health Research Centre,University of Manchester,Manchester,UK.
authors: A E P
authors: AE
authors: Heazell
authors: Institute of Reproductive and Developmental Biology,Imperial College London,Hammersmith Campus,Du Cane Road,London W12 0NN,UK.
authors: V
authors: V
authors: Glover
authors: Cardiff School of Biosciences,Cardiff University,Cardiff CF10 3AX,UK.
authors: R M
authors: RM
authors: John
mesh_terms: D000328:Adult; D015331:Cohort Studies; D003863:Depression / Q000235:genetics / Q000378:metabolism*; D004739:England; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010928:Placental Lactogen / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000378:metabolism*; D012737:Sex Factors
chemical_list: D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; D010928:Placental Lactogen
keywords: 
                 PEG3
              ; Human placental lactogen; prenatal depression