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30 - Transgenerational risks by exposure in utero

from Section 5 - Pathology

Published online by Cambridge University Press:  05 October 2013

By
Miguel A. Velazquez  and
Tom P. Fleming
Edited by
Alan Trounson ,
Roger Gosden  and
Ursula Eichenlaub-Ritter
Miguel A. Velazquez
Affiliation:
Centre for Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK
Tom P. Fleming
Affiliation:
Centre for Biological Sciences, University of Southampton, Southampton General Hospital, Southampton, UK
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

A significant proportion of human deaths worldwide are caused by non-communicable diseases (NCDs) and it has been estimated that by 2030 NCDs will account for over 60% of human mortality in both economically developed and developing countries [1]. Experimental trials in animals and epidemiological and clinical studies in humans have revealed that development of NCDs in adult life can be programmed during the prenatal period [2–8]. This adverse programming is the basis of the developmental origins of health and disease (DOHaD) concept [7]. Several lines of evidence indicate that this detrimental programming can be induced not only during fetal development but also during the preimplantation period [3, 4, 6, 7, 9]. However, this unfavorable programming can also be exerted before conception. In mammals, events occurring during primordial germ cell generation, oogonia differentiation, primordial oocyte formation, and folliculogenesis can have an impact on oocyte developmental competence (Figure 30.1). Accordingly, it has long been recognized that mammalian oocytes rely on unperturbed maternal mRNA stored during oogenesis to reach proper cytoplasmic and nuclear maturation, which is essential for successful fertilization and the first cell divisions of the newly formed embryo [10]. Likewise, successive developmental stages such as blastocyst formation, implantation, and fetal development can also be influenced by oocyte quality [7, 9, 11]. Growing evidence also indicates that oocyte developmental competence acquired during folliculogenesis can critically affect the development of NCDs in adulthood [9, 11]. Of further significance is the transgenerational non-genomic transmission of phenotypes caused by adverse uterine environments beyond the F1 generation [2, 12, 13], suggesting a possible effect on events involved in oocyte formation during fetal development. This chapter will focus on the available evidence supporting the notion that maternal challenges affecting folliculogenesis in postnatal life or oogenesis during fetal development can program the development of NCDs in offspring adult life across generations.

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Type
Chapter
Information
Biology and Pathology of the Oocyte
Role in Fertility, Medicine and Nuclear Reprograming
 , pp. 353 - 361
Publisher: Cambridge University Press
Print publication year: 2013

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