TY - JOUR

T1 - Placental DNA methylation in pregnancies complicated by maternal diabetes and/or obesity

T2 - State of the art and research gaps

AU - Hjort, Line

AU - Novakovic, Boris

AU - Cvitic, Silvija

AU - Saffery, Richard

AU - Damm, Peter

AU - Desoye, Gernot

PY - 2022

Y1 - 2022

N2 - Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in pregnancies complicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy outcome, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in pregnancies complicated by diabetes and obesity.

AB - Maternal diabetes and/or obesity in pregnancy are undoubtedly associated with later disease-risk in the offspring. The placenta, interposed between the mother and the foetus, is a potential mediator of this risk through epigenetic mechanisms, including DNA methylation. In recent years, multiple studies have identified differentially methylated CpG sites in the placental tissue DNA in pregnancies complicated by diabetes and obesity. We reviewed all published original research relevant to this topic and analysed our findings with the focus of identifying overlaps, contradictions, and gaps. Most studies focused on the association of gestational diabetes and/or hyperglycaemia in pregnancy and DNA methylation in placental tissue at term. We identified overlaps in results related to specific candidate genes, but also observed a large research gap of pregnancies affected by type 1 diabetes. Other unanswered questions relate to analysis of specific placental cell types and the timing of DNA methylation change in response to diabetes and obesity during pregnancy. Maternal metabolism is altered already in the first trimester involving structural and functional changes in the placenta, but studies into its effects on placental DNA methylation during this period are lacking and urgently needed. Foetal sex is also an important determinant of pregnancy outcome, but only few studies have taken this into account. Collectively, we provide a reference work for researchers working in this large and evolving field. Based on the results of the literature review, we formulate suggestions for future focus of placental DNA methylation studies in pregnancies complicated by diabetes and obesity.

KW - Pregnancy

KW - placenta

KW - epigenetic

KW - DNA methylation

KW - gestational diabetes

KW - type 1 diabetes

KW - type 2 diabetes

KW - obesity

KW - hyperglycaemia

KW - hyperlipidaemia

KW - foetal development

KW - offspring

KW - IMPRINTED GENES

KW - CORD BLOOD

KW - EPIGENETIC REGULATION

KW - DOWN-REGULATION

KW - FETAL SEX

KW - MELLITUS

KW - EXPRESSION

KW - RECEPTOR

KW - GLUCOSE

KW - ASSOCIATION

U2 - 10.1080/15592294.2022.2111755

DO - 10.1080/15592294.2022.2111755

M3 - Review

C2 - 35950598

VL - 17

SP - 2188

EP - 2208

JO - Epigenetics

JF - Epigenetics

SN - 1559-2294

IS - 13

ER -