Maternal prenatal depression is associated with decreased placental expression of the imprinted gene PEG3

Abstract

BackgroundMaternal 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.MethodA 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.ResultsIn 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).ConclusionsThis 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.

Prenatal parenting

“…It has been shown to be important in nest building and nurturing behaviour in rodents (Champagne and Curley, 2009). We have recently shown in three independent cohorts that prenatal maternal depression is associated with a down regulation of placental PEG3 expression (Janssen et al, 2016). It is of interest in this regard that it has been found that women with high depressive symptom scores during mid pregnancy, but not when their infants were 8 months, had a 30% increased risk of low maternal responsiveness when the infant was 12 months compared to women with consistently low depression (Pearson et al, 2012b).…”

“…The fetal genome regulates maternal physiology and behaviour via the placenta too (Broad and Keverne, 2011). The placenta produces hormones that act on the maternal hypothalamus, and can alter later mothering behaviour (Janssen et al 2016). The peptide PEG3 is of especial interest with regards to this.…”

A Role for the Placenta in Programming Maternal Mood and Childhood Behavioural Disorders

“…). Consistent with this hypothesis, recent data have identified a significant association between both symptoms of prenatal depression and clinically diagnosed depression with placental expression of both an imprinted gene and placental lactogen, a hormone predicted to be regulated by this gene . Determining the cause and effect relationships in human studies of pregnancy is challenging.…”

A Potential Role for Insulin Treatment During Pregnancy in Reducing Postpartum Psychological Distress in Maternal Obesity: An Administrative Population Health Study

“…Equally so, certain neurological changes in the mother must also occur in order to facilitate appropriate and proper care for her newborn [17]. In two recent studies, PL was linked to depression [22,23]. In the rst study [23], placenta samples from women with clinically diagnosed prenatal depression and as well as in those self-reporting signi cant symptoms of depression during pregnancy were found to have a signi cantly decreased level of PL ribonucleic acid (RNA) [23].…”

“…In two recent studies, PL was linked to depression [22,23]. In the rst study [23], placenta samples from women with clinically diagnosed prenatal depression and as well as in those self-reporting signi cant symptoms of depression during pregnancy were found to have a signi cantly decreased level of PL ribonucleic acid (RNA) [23]. In the second study [22], maternal serum PL taken just before birth was negatively associated with depression and anxiety scores assessed 10 weeks after birth.…”