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Background   H19  and  IGF2  genes are imprinted and involved in regulating fetal and placental growth. The  H19  differentially methylated region (DMR) is paternally methylated and maternally unmethylated and regulates the imprinted expression of  H19  and  IGF2 . Epimutation at the  H19 -DMR in humans results in congenital growth disorders, Beckwith-Wiedemann and Silver-Russell syndromes, when erroneously its maternal allele becomes methylated and its paternal allele becomes unmethylated, respectively. Although  H19  and  IGF2  have been assessed for their involvement in pregnancy complications including fetal growth restriction (FGR) and pregnancy-induced hypertension (PIH)/hypertensive disorder of pregnancy (HDP) intensively in the last decade, it is still not established whether epimutation at the  H19 -DMR in the placenta results in pathogenic conditions in pregnancy. We aimed to assess the frequency of  H19 -DMR epimutation and its effects on the allelic expression patterns of  H19  and  IGF2  genes among normal and abnormal pregnancy cases.    Results  We enrolled two independently collected sets of placenta samples from normal pregnancies as controls and common pregnancy complications, FGR and PIH (HDP). The first set consisted of 39 controls and 140 FGR and/or PIH cases, and the second set consisted of 29 controls and 62 cases. For these samples, we initially screened for DNA methylation changes at  H19 -DMR and  IGF2 -DMRs by combined bisulfite restriction analysis, and further analyzed cases with methylation changes for their allelic methylation and expression patterns. We identified one case each of FGR and PIH showing hypomethylation of  H19 -DMR and  IGF2 -DMRs only in the placenta, but not in cord blood, from the first case/control set. For the PIH case, we were able to determine the allelic expression pattern of  H19  to be biallelically expressed and the  H19/IGF2  expression ratio to be highly elevated compared to controls. We also identified a PIH case with hypomethylation at  H19 -DMR and  IGF2 -DMRs in the placenta from the second case/control set.    Conclusions  Placental epimutation at  H19 -DMR was observed among common pregnancy complication cases at the frequency of 1.5% (3 out of 202 cases examined), but not in 68 normal pregnancy cases examined. Alteration of  H19/IGF2  expression patterns due to hypomethylation of  H19 -DMR may have been involved in the pathogenesis of pregnancy complications in these cases.    Electronic supplementary material  The online version of this article (10.1186/s13148-019-0712-3) contains supplementary material, which is available to authorized users.

Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2