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

School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman, WA 99164-4660, USA.
Trends in Genetics (Impact Factor: 9.92). 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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    • "During adult human life, about 400 oocytes eventually reach maturation and are ovulated, finally leading to menopause [Baird et al. 2005; Faddy et al. 1992; Kaipia and Hsueh 1997]. As primordial follicles are arrested at dictyotene stage of meiosis for many years, the follicles during this long waiting period undergo degenerative change which is due to the action of environmental factors that can damage DNA [Baird et al. 2005; Eichenlaub-Ritter 2012; Hunt and Hassold 2008; Tarin 1996]. These degenerative changes which include DNA double strand breaks (DSBs) due to oxidative stress and other causative agents over time have been hypothesized to be a cause of ovarian aging and oocyte loss [Aitken 2014; Kurus et al. 2013; Titus et al. 2013]. "
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    ABSTRACT: Age related decline in reproductive performance in women is well documented and apoptosis has been considered as one of the reasons for the decline of primordial follicle reserve. Recently we observed a decline in the efficiency of DNA repair ability in aged rat primordial follicles as demonstrated by decreased mRNA levels of DNA repair genes BRCA1 and H2AX. In the present study, a two-dimensional electrophoresis (2DE) proteomic approach was employed to identify differentially expressed proteins in primordial follicles isolated from ovaries of immature (∼20 days) and aged (∼400-450 days) rats. Using MALDI-TOF/TOF MS, we identified 13 differentially expressed proteins (p < 0.05) which included seven up-regulated and six down-regulated proteins in aged primordial follicles. These proteins are involved in a wide range of biological functions including apoptosis, DNA repair, and the immune system. Interestingly, the differentially expressed proteins such as FIGNL1 (DNA repair) and BOK (apoptotic protein) have not been previously reported in the rat primordial follicles and these proteins can be related to some common features of ovarian aging such as loss of follicle reserve and genome integrity. The quantitative differences of two important proteins BOK and FIGNL1 observed by the proteomic analysis were correlated with the transcript levels, as determined by semi-quantitative RT-PCR. Our results improve the current knowledge about protein factors associated with molecular changes in rat primordial follicles as a function of aging and our understanding of the proteomic processes involved in degenerative changes observed in aging primordial follicles.
    Systems biology in reproductive medicine 09/2015; DOI:10.3109/19396368.2015.1077903 · 1.60 Impact Factor
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    • "This process requires precise control of homologous chromosome pairing and genetic recombination to secure accurate chromosome segregation and transferring of genetic materials to the next generation. Therefore, defects in meiotic progression cause aneuploidy, which leads to reproductive failure and congenital birth defects as evidenced by 7–10% of chromosomally abnormal pregnancies in humans (Hunt and Hassold 2008). Although a higher frequency of deleterious consequences arise from meiotic defects, relatively fewer studies have focused on the mechanisms underlying accurate meiotic rather than mitotic cell divisions, especially in multicellular systems. "
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    ABSTRACT: Although a growing number of studies have reported the importance of SUMOylation in genome maintenance and DNA double-strand break repair (DSBR), relevant target proteins and how this modification regulates their functions are yet to be clarified. Here, we analyzed SUMOylation of ZTF-8, the homolog of mammalian RHINO, to test the functional significance of this protein modification in the DSBR and DNA damage response (DDR) pathways in the Caenorhabditis elegans germline. We found that ZTF-8 is a direct target for SUMOylation in vivo and that its modification is required for DNA damage checkpoint induced apoptosis and DSBR. Non-SUMOylatable mutants of ZTF-8 mimic the phenotypes observed in ztf-8 null mutants including reduced fertility, impaired DNA damage repair and defective DNA damage checkpoint activation. However, while mutants for components acting in the SUMOylation pathway fail to properly localize ZTF-8, its localization is not altered in the ZTF-8 non-SUMOylatable mutants. Taken together, these data show that direct SUMOylation of ZTF-8 is required for its function in DSBR as well as DDR but not its localization. ZTF-8's human ortholog is enriched in the germline, but its meiotic role as well as its post-translational modification has never been explored. Therefore, our discovery may assist in understanding the regulatory mechanism of this protein in DSBR and DDR in the germline. Copyright © 2015, The Genetics Society of America.
    Genetics 03/2015; 200(2). DOI:10.1534/genetics.115.175661 · 5.96 Impact Factor
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    • "To investigate the role of the Y centromere structure on chromosome stability we have used two spontaneous laboratory mouse mutant strains, BALB/cWt and A/HeJ, that are associated with a high incidence of hermaphroditism [9], [10]. Both mutant strains display high rates of Y chromosome non-disjunction when compared to inbred strains that carry their progenitor Y chromosome [11], [12], [13]. It has been hypothesized that mutations at or near the Y centromere may contribute to the chromosome instability phenotype [14]. "
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    ABSTRACT: The centromere is an essential chromosomal structure that is required for the faithful distribution of replicated chromosomes to daughter cells. Defects in the centromere can compromise the stability of chromosomes resulting in segregation errors. We have characterised the centromeric structure of the spontaneous mutant mouse strain, BALB/cWt, which exhibits a high rate of Y chromosome instability. The Y centromere DNA array shows a de novo interstitial deletion and a reduction in the level of the foundation centromere protein, CENP-A, when compared to the non-deleted centromere array in the progenitor strain. These results suggest there is a lower threshold limit of centromere size that ensures full kinetochore function during cell division.
    PLoS ONE 01/2014; 9(1):e86875. DOI:10.1371/journal.pone.0086875 · 3.23 Impact Factor
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