BACKGROUND: 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. METHOD: 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. RESULTS: 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). CONCLUSIONS: 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.The Manchester cohort
was supported by Manchester National Institute
for Health Research (NIHR) Biomedical Research.
The Queen Charlotte’s cohort was supported by the
Medical Research Council (MRC) (Eurostress),
National Institutes of Health (R01MH073842) and the
Genesis Research Trust. The MBAM cohort was supported
by the Genesis Research Trust. A.B.J. was supported
by a Biotechnology and Biological Sciences
Research Council (BBSRC) Doctoral Training Grants
(DTG) studentship and subsequently MRC project
grant MR/M013960/1. S.J.T. was supported by BBSRC
project grant BB/J015156/1. L.E.C. was supported by
an Imperial College London Ph.D. studentship and
both L.E.C. and P.G.R were supported by the NIHR
Imperial Biomedical Research Centre