Placenta-specific epimutation at H19-DMR among common pregnancy complications: its frequency and effect on the expression patterns of H19 and IGF2
| Autor: | Hisanori Minakami, Takahiro Yamada, Kiyoko Kato, Kazuhiko Nakabayashi, Kenichiro Hata, Rina Akaishi, Kentaro Matsuoka, Norio Wake, Junko Tomikawa, Hiromi Kamura, Chiharu Tayama, Yuko Yamaguchi |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Genomic imprinting Placenta Abnormal Pregnancy Andrology 03 medical and health sciences 0302 clinical medicine Insulin-Like Growth Factor II Pregnancy Combined bisulfite restriction analysis Genetics medicine Humans Epimutation Allele Molecular Biology Genetics (clinical) Hypertensive disorder of pregnancy Fetus DNA methylation H19 business.industry Research Fetal growth restriction IGF2 Fetal Blood medicine.disease female genital diseases and pregnancy complications Pregnancy Complications 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Pregnancy-induced hypertension Organ Specificity Case-Control Studies 030220 oncology & carcinogenesis embryonic structures Female RNA Long Noncoding business Developmental Biology |
| Zdroj: | Clinical Epigenetics |
| ISSN: | 1868-7083 1868-7075 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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