Aberrant methylation of IGF2-AS promoter in early pregnancy loss

Taiwan J Obstet Gynecol. 2020 Jan;59(1):109-114. doi: 10.1016/j.tjog.2019.11.017.

Abstract

Objective: The present study aimed to evaluate insulin-like growth factor 2 antisense (IGF2-AS) in the villi of human embryos and compared its expression between normal pregnancy and early pregnancy loss (EPL).

Materials and methods: The present study conducted a microarray analysis to identify the expression profiles of lncRNAs in villi from EPL and normal controls (controls, n = 10 and EPL patients, n = 10). Embryonic villi were collected from women who underwent artificial abortion. QPCR was used to confirm the results. The DNA methylation patterns were analyzed using pyrosequencing and bisulfite sequencing polymerase chain reaction. The percentage of methylation was compared in chorionic villi from the two groups.

Results: A total of 57 deregulated differentially expressed lncRNAs were detected, of which 33 were upregulated, and 24 were downregulated. The expression of lncRNA IGF2-AS was downregulated significantly in EPL villi compared with the normal villi. Negative regulation of IGF2-AS may be involved in the development of EPL. Methprimer predicted that IGF2-AS promoter had CpG islands and dense CG sites. Increased methylation at CpG islands present in IGF2-AS gene promoter was observed in EPL villi.

Conclusion: An increase in methylation of IGF2-AS likely leads to its downregulation in chorionic villi of EPL. The findings suggest that a deficiency of IGF2-AS in the villi is associated with human EPL.

Keywords: Early pregnancy loss; IGF2-AS; Methylation; Villus.

Publication types

  • Evaluation Study

MeSH terms

  • Abortion, Spontaneous / genetics*
  • Adult
  • Case-Control Studies
  • Chorionic Villi / metabolism*
  • CpG Islands / genetics
  • DNA Methylation / genetics*
  • Down-Regulation / genetics
  • Female
  • Humans
  • Pregnancy
  • Promoter Regions, Genetic
  • Proteins / metabolism*
  • RNA, Long Noncoding / metabolism*
  • Up-Regulation / genetics

Substances

  • IGF2-AS lncRNA, human
  • Proteins
  • RNA, Long Noncoding