Celulas ovogenicas y no disyuncion

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Curr Opin Pediatr. Author manuscript; available in PMC 2010 December 1.
Published in final edited form as: Curr Opin Pediatr. 2009 December ; 21(6): 703–708. doi:10.1097/MOP.0b013e328332c6ab.

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Maternal age and chromosomally abnormal pregnancies: what we know and what we wish weknew
Terry Hassold and Patricia Hunt School of Molecular Biosciences and Center for Reproductive Biology, Washington State University Pullman, WA 99164

Abstract
Purpose of review—The relationship between increasing maternal age and trisomy has been recognized for over 50 years and is one of the most important etiological factors associated with any human genetic disorder. Specifically, therisk of trisomy in a clinically recognized pregnancy rises from about 2–3% for women in their twenties to an astounding 30% or more for women in their forties. Thus, as women approach the end of their child-bearing years, errors of chromosome segregation represent the most important impediment to a successful pregnancy. Recent findings—Despite the clinical importance of this relationship, we do notunderstand how age affects the likelihood of producing a normal egg. Errors that affect chromosome segregation could occur at several stages during the development of the oocyte: in the fetal ovary, either during the mitotic proliferation of oogonia or the early stages of meiosis; in the “dictyate” oocyte, during the 10–50 year period of meiotic arrest; or during the final stages of oocyte growthand maturation, when meiosis resumes and the meiotic divisions take place. Recent evidence from studies of human oocytes and trisomic conceptions and from studies in model organisms implicates errors at each of these stages Summary—It seems likely that there are multiple causes of human age-related nondisjunction, complicating our efforts to understand – and, ultimately, to provide preventativemeasures for – errors associated with increasing maternal age. Keywords trisomy; maternal age; recombination

Introduction
The association between advancing maternal age and trisomy is one of the best-known and longest recognized risk factors for any human genetic defect. As early as 1933 – a quarter century before the identification of trisomy 21 by Lejeune et al [1] – Penrose recognized thatDown syndrome was more common in older women [2]. Studies in the 1960–1980s confirmed and extended these observations, and it is now clear that increasing age of the women increases the likelihood of trisomy for most, if not all, human chromosomes [3,4]. However, our understanding of the basis of the age effect has not matched our understanding of the clinical

Corresponding author: Terry Hassold,302EA BLS Building, Center for Reproductive Biology, Washington State University, Pullman, WA 99164, Tel: 509-335-2473, terryhassold@wsu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and reviewof the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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importance of the effect; indeed, we know little more about the underlying causes of the age effect than did either Penrose orLejeune.

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Fortunately, this situation may finally be changing. Large-scale analyses of the origin of trisomy 21, new approaches to the study of human gametes, and mutational analyses of model organisms have begun to shed light on processes that mediate nondisjunctional risks. In this review, we summarize these...