Human female meiosis: what makes a good egg go bad?

School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164-4660, USA.
Trends in Genetics (Impact Factor: 11.6). 03/2008; 24(2):86-93. DOI: 10.1016/j.tig.2007.11.010
Source: PubMed

ABSTRACT Critical events of oogenesis occur during three distinct developmental stages: meiotic initiation in the fetal ovary, follicle formation in the perinatal period, and oocyte growth and maturation in the adult. Evidence from studies in humans and mice suggests that the genetic quality of the egg may be influenced by events at each of these stages. Recent experimental studies add additional complexity, suggesting that environmental influences might adversely affect all three stages. Thus, understanding the molecular control of oogenesis during these critical developmental windows will not only contribute to an understanding of human aneuploidy, but also provide a means of assessing potential effects of environmental exposures on human reproductive health.

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    ABSTRACT: Obesity, diabetes, and related metabolic disorders are major health issues worldwide. As the epidemic of metabolic disorders continues, the associated medical co-morbidities, including the detrimental impact on reproduction, increase as well. Emerging evidence suggests that the effects of maternal nutrition on reproductive outcomes are likely to be mediated, at least in part, by oocyte metabolism. Well-balanced and timed energy metabolism is critical for optimal development of oocytes. To date, much of our understanding of oocyte metabolism comes from the effects of extrinsic nutrients on oocyte maturation. In contrast, intrinsic regulation of oocyte development by metabolic enzymes, intracellular mediators, and transport systems is less characterized. Specifically, decreased acid transport proteins levels, increased glucose/lipid content and elevated reactive oxygen species in oocytes have been implicated in meiotic defects, organelle dysfunction and epigenetic alteration. Therefore, metabolic disturbances in oocytes may contribute to the diminished reproductive potential experienced by women with metabolic disorders. In-depth research is needed to further explore the underlying mechanisms. This review also discusses several approaches for metabolic analysis. Metabolomic profiling of oocytes, the surrounding granulosa cells, and follicular fluid will uncover the metabolic networks regulating oocyte development, potentially leading to the identification of oocyte quality markers and prevention of reproductive disease and poor outcomes in offspring.
    Cellular and Molecular Life Sciences CMLS 10/2014; 72(2). DOI:10.1007/s00018-014-1739-4 · 5.86 Impact Factor
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    ABSTRACT: Down syndrome represents the most frequent live born aneuploidy and genetic form of intellectual disability. The overwhelming majority of live born Down syndrome is caused by trisomy 21 condition, although a small fraction is due to the inheritance of de novo translocated chromosome 21. The extra copy of chromosome 21 originates owing to non-separation or nondisjunction of chromosome at anaphase in meiotic cell division of gametogenesis. Sincere research attempt have recognized that the higher incidence of Down syndrome birth is associated with maternal advanced age of conception and reduced recombination on chromosome 21. Using panel of short tandem repeat (STR) markers scientists have proved for overwhelming majority of cases, the error originates in maternal first meiotic division when the oocyte grows in fetal ovary and the maternal age effect is restricted only to these maternally originated cases. Several hypotheses have been proposed to explain this maternal age associated increase in the incidence of Down syndrome birth. With large population sample and refined analytical approaches scientists have determined that the effect of recombination error on the nondisjunction is bimodal. On one hand, overall reduction in recombination frequency imparts a risk of nondisjunction irrespective of maternal age. On other hand, some susceptible chiasma configurations increase the chance of chromosome malsegregation with advancing maternal age. Thus the risk factors for the chromosome 21 nondisjunction are of two categories namely, maternal age independent and maternal age dependent. Beside these, some genetic polymorphisms show high degree of susceptibility for Down syndrome conception among women. The gene MTHFR is such candidate which is actually involved in folic acid metabolism pathway and its specific polymorphisms exhibits predisposition to missegregation of Ch21 irrespective of ethnicity of population across the globe. The present review is focused to address the latest development in understanding the role of genetic and molecular risk factors for Down syndrome birth. Keywords: Down syndrome; Nondisjunction; Maternal Age; Recombination; Genetic polymorphism


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