Potential significance of genomic imprinting defects for reproduction and assisted reproductive technology

Abstract

Recent studies suggest a possible link between human assisted reproductive technology and genomic imprinting disorders. Assisted reproductive technology includes the isolation, handling and culture of gametes and early embryos at times when imprinted genes are likely to be particularly vulnerable to external influences. Evidence of sex-specific differences in imprint acquisition suggests that male and female germ cells may be susceptible to perturbations in imprinted genes at specific prenatal and postnatal stages. Imprints acquired first during gametogenesis must be maintained during preimplantation development when reprogramming of the overall genome occurs. In this review, we will discuss both new developments in our understanding of genomic imprinting including the mechanisms and timing of imprint erasure, acquisition and maintenance during germ cell development and early embryogenesis as well as the implications of this research for future epigenetic studies in reproduction and assisted reproductive technology.

The impact of ovarian stimulation for IVF on the developing embryo

“…Epigenetic mechanisms regulate gene activity in a hereditary fashion without affecting the genetic constitution (Lucifero et al 2004). Gene imprinting is an epigenetic process, which allows a subset of genes to be expressed in a monoallelic parent-of-origin manner (Lawrence & Moley 2008).…”

“…The main epigenetic mechanisms controlling imprinting are DNA methylation and histone modification. DNA methylation is the best characterised epigenetic modification and in many cases occurs in a differentially methylated region (DMR; Lucifero et al 2004).…”

“…In the male, remethylation starts early during embryonic development in the gonocytes and continues up to the spermatogonia stage; whereas, in the female, it begins after birth, early in the oocyte growth phase, continuing throughout oocyte growth (Zamudio et al 2008). In humans, little information is available on imprinting dynamics, but existing data suggest some conservation of the epigenetic mechanisms described in the mouse (Lucifero et al 2004).…”

Gamete imprinting: setting epigenetic patterns for the next generation

“…Several recent studies have linked the genomic imprinting disorders Beckwith-Wiedemann syndrome (DeBaun et al 2003;Gicquel et al 2003;Maher et al 2003;Halliday et al 2004) and Angelman syndrome (Cox et al 2002;Orstavik et al 2003) with the use of assisted reproductive technologies (Lucifero et al 2004b). In the case of the genomic imprinting disorders, the absence of maternal methylation imprints was found, involving the KCNQT1OT1 locus in BeckwithWiedemann syndrome and the SNRPN locus in Angelman syndrome.…”

Effects of Aroclor 1254 on the Dna Methylation of Imprinted Genes in the Adult Mouse Sperm

“…It is also reversible in that the methylation imprints are switched in the germ line to reflect the sex of the parent (Li et al, 1993). Evidence of sex-specific differences in imprint acquisition suggests that male and female germ cells may be susceptible to perturbations in imprinted genes at specific prenatal and postnatal stages (Lucifero et al, 2004). Germ cells are a unique cell type that can transmit genetic information to the next generation.…”