Expression of imprinted genes in placenta is associated with infant neurobehavioral development

Green, Benjamin B.; Kappil, Maya; Lambertini, Luca; Armstrong, David A.; Guerin, Dylan J.; Sharp, Andrew J.; Lester, Barry M.; Chen, Jia; Marsit, Carmen J.

doi:10.1080/15592294.2015.1073880

Cited by 51 publications

(41 citation statements)

References 44 publications

(51 reference statements)

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“…These genes have been suggested as potential mediators of adverse infant outcomes because of their well-established roles in controlling fetal growth, placental development, adult behaviour and metabolism (Lefebvre et al 1998; Li et al 1999; Curley et al 2005; Smith et al 2006; Tunster et al 2013; Jensen et al 2014; McNamara & Isles, 2014). Aberrant expression of imprinted genes in the placenta has also been demonstrated to be associated with impaired infant neurobehavioural development in humans (Green et al 2015). Recent studies demonstrate that a subset of imprinted genes converge on the endocrine lineages of the mouse placenta to regulate placental hormone production (John, 2013).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…Many of the placental imprinted genes associated with PM 2.5 have important functions in the brain and in neurodevelopment such as CDKN1C, FAM50B, NPAP1, PHLDA2, SLC22A18AS, SHANK2 , and UBE3A . Expression of three of these genes ( PHLDA2, NPAP1, FAM50B ) has been previously linked with child neurological function in this same cohort (Green et al 2015). Additionally, NPAP1and UBE3A are found in a segment on chromosome 15 that plays a critical role in three neurogenetic disorders (Chamberlain 2013).…”

Section: Discussionmentioning

confidence: 76%

Maternal residential air pollution and placental imprinted gene expression

Kingsley

Deyssenroth

Kelsey

et al. 2017

Environment International

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Background Maternal exposure to air pollution is associated with reduced fetal growth, but its relationship with expression of placental imprinted genes (important regulators of fetal growth) has not yet been studied. Objectives To examine relationships between maternal residential air pollution and expression of placental imprinted genes in the Rhode Island Child Health Study (RICHS). Methods Women-infant pairs were enrolled following delivery between 2009 and 2013. We geocoded maternal residential addresses at delivery, estimated daily levels of fine particulate matter (PM2.5; n=355) and black carbon (BC; n=336) using spatial-temporal models, and estimated residential distance to nearest major roadway (n=355). Using linear regression models we investigated the associations between each exposure metric and expression of nine candidate genes previously associated with infant birthweight in RICHS, with secondary analyses of a panel of 108 imprinted genes expressed in the placenta. We also explored effect measure modification by infant sex. Results PM2.5 and BC were associated with altered expression for seven and one candidate genes, respectively, previously linked with birthweight in this cohort. Adjusting for multiple comparisons, we found that PM2.5 and BC were associated with changes in expression of 41 and 12 of 108 placental imprinted genes, respectively. Infant sex modified the association between PM2.5 and expression of CHD7 and between proximity to major roadways and expression of ZDBF2. Conclusions We found that maternal exposure to residential PM2.5 and BC was associated with changes in placental imprinted gene expression, which suggests a plausible line of investigation of how air pollution affects fetal growth and development.

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“…In an ideal setting, exposures would be quantified from repeated psychological or laboratory measurements, augmented by in depth analysis of the placenta (Green et al, 2015;Vasung et al, 2018), as well as both maternal and infant genetic information. In an ideal setting, exposures would be quantified from repeated psychological or laboratory measurements, augmented by in depth analysis of the placenta (Green et al, 2015;Vasung et al, 2018), as well as both maternal and infant genetic information.…”

Section: Key Challengesmentioning

confidence: 99%

Prenatal exposures and infant brain: Review of magnetic resonance imaging studies and a population description analysis

Pulli

Kumpulainen

Kasurinen

et al. 2018

Human Brain Mapping

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Brain development is most rapid during the fetal period and the first years of life. This process can be affected by many in utero factors, such as chemical exposures and maternal health characteristics. The goal of this review is twofold: to review the most recent findings on the effects of these prenatal factors on the developing brain and to qualitatively assess how those factors were generally reported in studies on infants up to 2 years of age. To capture the latest findings in the field, we searched articles from PubMed 2012 onward with search terms referring to magnetic resonance imaging (MRI), brain development, and infancy. We identified 19 MRI studies focusing on the effects of prenatal environment and summarized them to highlight the recent advances in the field. We assessed population descriptions in a representative sample of 67 studies and conclude that prenatal factors that have been shown to affect brain metrics are not generally reported comprehensively. Based on our findings, we propose some improvements for population descriptions to account for plausible confounders and in time enable reliable meta‐analyses to be performed. This could help the pediatric neuroimaging field move toward more reliable identification of biomarkers for developmental outcomes and to better decipher the nuances of normal and abnormal brain development.

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Expression of imprinted genes in placenta is associated with infant neurobehavioral development

Cited by 51 publications

References 44 publications

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

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

Maternal residential air pollution and placental imprinted gene expression

Prenatal exposures and infant brain: Review of magnetic resonance imaging studies and a population description analysis

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