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33 - Oocyte epigenetics and the risks for imprinting disorders associated with assisted reproduction

from Section 5 - Pathology

Published online by Cambridge University Press:  05 October 2013

By
Serge McGraw  and
Jacquetta M. Trasler
Edited by
Alan Trounson ,
Roger Gosden  and
Ursula Eichenlaub-Ritter
Serge McGraw
Affiliation:
Departments of Pediatrics, Human Genetics, and Pharmacology and herapeutics, McGill University and of the Research Institute of the McGill University Health Centre at the Montreal Children’s Hospital, Montreal, Canada
Jacquetta M. Trasler
Affiliation:
Departments of Pediatrics, Human Genetics, and Pharmacology and herapeutics, McGill University and of the Research Institute of the McGill University Health Centre at the Montreal Children’s Hospital, Montreal, Canada
Alan Trounson
Affiliation:
California Institute for Regenerative Medicine
Roger Gosden
Affiliation:
Center for Reproductive Medicine and Infertility, Cornell University, New York
Ursula Eichenlaub-Ritter
Affiliation:
Universität Bielefeld, Germany
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Summary

Introduction

As a treatment for female infertility, assisted reproductive technology (ART) commonly uses a number of treatments and manipulations, including hormonal stimulation of follicular development and ovulation, cryopreservation, in vitro maturation (IVM), in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) and embryo culture, all of which could adversely affect oocyte development or function during early embryogenesis. Over the last decade, concern has been raised about possible increases in the occurrence of rare genomic imprinting disorders, in particular Beckwith–Wiedemann syndrome (BWS) and Angelman syndrome (AS), in ART-conceived children. The genomic imprinting disorders seen in children conceived using ART were accompanied in many cases by a loss of maternal DNA methylation at imprinted loci. Genomic imprinting refers to the acquisition of a unique epigenetic profile in a small subset of genes during gametogenesis. This differential epigenetic mark in the gametes results in a parent-of-origin-specific expression of these imprinted genes in the offspring. Most imprinted genes exist in clusters in the genome and their allele-specific expression is regulated by sequence elements called imprinting control regions (ICRs). Genomic imprinting is under the control of epigenetic mechanisms including DNA methylation at ICRs, also known as differentially methylated domains or regions (DMDs, DMRs). One of the best studied epigenetic mechanisms, DNA methylation, is heritable and reversible and susceptible to being perturbed during development. At most ICRs, DNA methylation occurs in the female germ line and is inherited from the mother. Following fertilization, male and female gametic imprints must be maintained through preimplantation development and into adulthood. Thus any factor that affects the ability of oocytes to acquire imprints or normal epigenetic patterns during oogenesis or maintain these patterns after fertilization could potentially predispose to imprinting disorders in the offspring. This chapter reviews current data on the effects of ART on genomic imprinting in humans, along with the human and animal research that is beginning to help explain how perturbations in oocyte biology may be linked to the etiology of ART-associated epigenetic dysregulation and abnormalities in genomic imprinting.

Type
Chapter
Information
Biology and Pathology of the Oocyte
Role in Fertility, Medicine and Nuclear Reprograming
 , pp. 384 - 393
Publisher: Cambridge University Press
Print publication year: 2013

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