Prenatal Environmental Stressors and DNA Methylation Levels in Placenta and Peripheral Tissues of Mothers and Neonates Evaluated by Applying Artificial Neural Networks

Andrea Stoccoro; Vanessa Nicolì; Fabio Coppedè; Enzo Grossi; Giorgio Fedrizzi; Simonetta Menotta; Francesca Lorenzoni; Marta Caretto; Arianna Carmignani; Sabina Pistolesi; Ernesto Burgio; Vassilios Fanos; Lucia Migliore

doi:10.3390/genes14040836

Prenatal Environmental Stressors and DNA Methylation Levels in Placenta and Peripheral Tissues of Mothers and Neonates Evaluated by Applying Artificial Neural Networks

Genes (Basel). 2023 Mar 30;14(4):836. doi: 10.3390/genes14040836.

Authors

Affiliations

¹ Department of Translational Research and of New Surgical and Medical Technologies, University of Pisa, 56126 Pisa, Italy.
² Autism Research Unit, Villa Santa Maria Foundation, 22038 Tavernerio, Italy.
³ Istituto Zooprofilattico Sperimentale della Lombardia e dell'Emilia Romagna, Chemical Department, Via P. Fiorini 5, 40127 Bologna, Italy.
⁴ Division of Neonatology and NICU, Department of Clinical and Experimental Medicine, 56126 Pisa, Italy.
⁵ Obstetrics and Gynecology Unit 1, Department of Experimental and Clinical Medicine, University of Pisa, 56126 Pisa, Italy.
⁶ Obstetrics and Gynecology Unit 2, Pisa University Hospital, 56126 Pisa, Italy.
⁷ First Division of Pathology, Department of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, Italy.
⁸ European Cancer and Environment Research Institute (ECERI), 1000 Brussels, Belgium.
⁹ Department of Surgical Sciences, University of Cagliari and Neonatal Intensive Care Unit, AOU Cagliari, 09124 Cagliari, Italy.
¹⁰ Department of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, Italy.

Abstract

Exposure to environmental stressors during pregnancy plays an important role in influencing subsequent susceptibility to certain chronic diseases through the modulation of epigenetic mechanisms, including DNA methylation. Our aim was to explore the connections between environmental exposures during gestation with DNA methylation of placental cells, maternal and neonatal buccal cells by applying artificial neural networks (ANNs). A total of 28 mother-infant pairs were enrolled. Data on gestational exposure to adverse environmental factors and on mother health status were collected through the administration of a questionnaire. DNA methylation analyses at both gene-specific and global level were analyzed in placentas, maternal and neonatal buccal cells. In the placenta, the concentrations of various metals and dioxins were also analyzed. Analysis of ANNs revealed that suboptimal birth weight is associated with placental H19 methylation, maternal stress during pregnancy with methylation levels of NR3C1 and BDNF in placentas and mother's buccal DNA, respectively, and exposure to air pollutants with maternal MGMT methylation. Associations were also observed between placental concentrations of lead, chromium, cadmium and mercury with methylation levels of OXTR in placentas, HSD11B2 in maternal buccal cells and placentas, MECP2 in neonatal buccal cells, and MTHFR in maternal buccal cells. Furthermore, dioxin concentrations were associated with placental RELN, neonatal HSD11B2 and maternal H19 gene methylation levels. Current results suggest that exposure of pregnant women to environmental stressors during pregnancy could induce aberrant methylation levels in genes linked to several pathways important for embryogenesis in both the placenta, potentially affecting foetal development, and in the peripheral tissues of mothers and infants, potentially providing peripheral biomarkers of environmental exposure.

Keywords: DNA methylation; DOHaD; artificial neural networks; dioxins; epigenetics; heavy metals; placenta; prenatal exposure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA Methylation*
Epigenesis, Genetic
Female
Humans
Infant
Infant, Newborn
Mothers
Mouth Mucosa / metabolism
Placenta* / metabolism
Pregnancy

Grants and funding

The project was funded by the National Centre for Disease Prevention and Control (CCM) of the Italian Ministry of Health (CCM 2017 “Ambiente, programmazione epigenetica fetale e prevenzione delle patologie croniche” (CUP E72F17000390001).