The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders

Curr Opin Obstet Gynecol. 2014 Jun;26(3):210-21. doi: 10.1097/GCO.0000000000000071.

Abstract

Purpose of review: Genomic imprinting refers to preferential allele-specific gene expression. DNA methylation-based molecular mechanisms regulate establishment and maintenance of parental imprints during early embryo development and gametogenesis. Because of the coincident timing, a potential association between assisted reproductive technology (ART) procedures and imprinting defects has been investigated in various studies. In this review, we provide an overview of genomic imprinting and present a summary of the relevant clinical data.

Recent findings: ART procedures affect DNA methylation pattern, parental imprinting status, and imprinted gene expression in the mouse embryo. In humans, several case series suggested an association between ART and imprinting disorders, with a three-fold to six-fold higher prevalence of ART use among children born with Beckwith-Wiedemann syndrome compared to the general population. However, more recent studies failed to support these findings and could not demonstrate an association between imprinting disorders and ARTs, independent of subfertility.

Summary: ART procedures may affect methylation status of imprinted regions in the DNA, leading to imprinting disorders. Although the low prevalence of imprinting disorders makes it challenging to perform conclusive clinical trials, further studies in large registries are required to determine the real impact of ARTs on their occurrence.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Beckwith-Wiedemann Syndrome / epidemiology
  • Beckwith-Wiedemann Syndrome / genetics*
  • DNA Methylation / genetics*
  • Epigenesis, Genetic
  • Female
  • Genomic Imprinting / genetics*
  • Humans
  • Infant, Newborn
  • Infertility / genetics*
  • Infertility / therapy
  • Male
  • Mice
  • Pregnancy
  • Reproductive Techniques, Assisted* / adverse effects
  • Risk Factors