The in utero developmental period represents a critical window during which parental lifestyle and environmental factors can impact the new-born epigenome, potentially altering the risk to develop disease throughout life until adulthood. Thus, it is of outmost importance to better understand the relationship between prenatal exposure to various stressors and epigenetic changes.
The aim of the current study was to apply artificial neural networks (ANNs) to unravel the connections among environmental exposure during gestation and concentrations of heavy metals and dioxins in placenta with gene specific and global methylation levels in DNA from placenta tissue, and from mother and infant buccal swab cells collected at the time of delivery.To this aim 26 mother-infants couples have been enrolled.
Information on lifestyle and environmental exposure during gestation have been obtained by administration of a questionnaire. Concentrations of various heavy metals and dioxins in placenta were analyzed by means of mass spectrometry.
Gene specific DNA methylation have been performed by means of methylation sensitive high-resolution melting, and global DNA methylation and hydroxymethylation using ELISA assays.ANNs analysis revealed interesting interactions among maternal stress during pregnancy and placental NR3C1 and maternal BDNF genes methylation, as well as among exposure to air pollutants and passive smoking during pregnancy and maternal MGMT and neonatal Erα genes methylation, respectively.
Strong correlations among placenta concentrations of different metals, including lead, chromium and cadmium and placenta OXTR, maternal and neonatal HSD11B2 and neonatal CYP1A1 and MECP2 genes methylation, respectively, have also been detected. Moreover, a strong correlation between dioxins concentrations and placenta MGMT gene methylation have been highlighted.Results of the current study show that methylation levels of genes involved in neurodevelopment, in the xenobiotic metabolism and in DNA repair are sensitive to various environmental stressors during pregnancy.
Altered methylation levels are detectable in placenta, potentially affecting foetal development, and in peripheral tissues of mothers and neonates, thus providing peripheral biomarkers of environmental exposure.

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1 Department of Translational Research and of New Surgical and Medical Technologies, Medical School, University of Pisa
2 Villa Santa Maria Foundation, Tavernerio (Como)
3 Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Bologna
4 Euro Mediterranean Scientific Biomedical Institute-ISBEM Research Centre, Mesagne (Brindisi)