Table 4.

Differentially methylated imprinted genes.

Genes	Protein/transcript	Chr. locus	Parental origin	Exposure	Change with exposure	Authors	Function (related to development of placenta and foetus)
C19MC	Chromosome 19 microRNA cluster	19q13.41	P	Pre-pregnancy BMI	↓	Prats-Puig et al [116]	miRNA cluster consisting of 46 genes, encoding 59 mature miRNAs, that are primate-specific and exclusively expressed in the placenta, embryonic stem cells and few cancers [63].
DLGAP2	DLG Associated Protein 2	8p23.3	M	GDM	↑	Houde et al [69]	Methylation may causally influence maternal insulin sensitivity [65].
DLGAP2				Hyperglycaemia	↑	Hivert et al [65]
DLK1	Delta Like Non-Canonical Notch Ligand 1	14q32.2	P	GDM	↑	Zhao et al [95]	DLK1-MEG3 imprinting locus associated with T1DM risk [125]. Predominant placental expression in vascular endothelial cells and pericytes, may play a pivotal role in development of these cells in placenta [126]. Hypomethylated DLK1 and H19 detected in Beckwith-Wiedeman-Syndrome [127]. Placental expression at term, but not in first trimester, tended to correlate with birthweight [57].
H19	long non-coding RNA	11p15	M	GDM	ns.	el Hajj et al [66]	Placental expression in first trimester, but not at term, correlated with crown rump length and tended to correlate with birth weight [57].
LIT1/ KCNQ1OT1	non-coding RNA	11p15.5	P	GDM	ns.	el Hajj et al [66]	Major genetic locus of Beckwith-Wiedeman-Syndrome [128]. Placental expression also altered in intrauterine growth restriction [128].
MEG3	Maternally Expressed 3	14q32.3	M	GDM	ns.	el Hajj et al [66]	Reduced expression in Intrauterine growth restriction [129]. Expression not correlated with birth weight or placental weight [57]. DLK1-MEG3 imprinting locus associated with T1DM risk [125].
MEG3				GDM	↑	Chen et al [92]
MEST	Mesoderm Specific Transcript	7q32.2	P/biallelic	GDM	↓	el Hajj et al [66]	Monoallelic expression in 81% of term placenta samples [57]. Differentially methylated in placentas of Small and large for gestational age [130]. No correlation between methylation and expression [130]. No expression correlation with birth weight [57]. Reduced placental methylation and increased expression in second trimester idiopathic spontaneous abortion [131].
NESPAS	long non-coding RNA	20q13.32	P	GDM	↓	el Hajj et al [66]	Antisense to NESP; encodes neuroendocrine secretory protein 55 in endocrine and brain tissues, considered neuron-specific [132]. Nothing known in placenta.
PEG3	Paternally Expressed 3	19q13.4	P/biallelic	GDM	ns.	el Hajj et al [66]	Monoallelic expression in 88% of term placenta samples [57]. Cord blood PEG3 methylation associates with placental weight [133]. Reduced expression in Intrauterine growth restriction [129]. No correlation between expression and birth weight [57].
SNRPN	SmallNuclear RibonucleoproteinPolypeptide N	15q11.2	P	GDM	ns.	el Hajj et al [66]	DNAm variation regulate normal placentation and placental disorders, is potentially susceptible to folic acid supplementation, and may be useful as novel foetal DNA marker in maternal plasma [134].
SNRPN				GDM	ns.	Binder et al [102]

Abbreviations: ns: non-significant, GDM: Gestational Diabetes Mellitus, T1DM: Type 1 Diabetes Mellitus, DNAm: DNA methylation.