Playing for half the deck: the molecular biology of meiosis

Champion, Mia D.; Hawley, R. Scott

doi:10.1038/nm-fertilitys50

Cited by 28 publications

(32 citation statements)

References 78 publications

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“…The basic features of meiosis, two cell divisions with no intervening DNA replication, result in halving of the chromosomal complement. Importantly, it is during the long prophase of meiotic division I (MI) that genetic recombination occurs, increasing the genetic variability of the organism (Champion and Hawley, 2002). Following engagement of the differentiation programme and migration of cells into the luminal compartment of colon there is abrupt downregulation of Ki67, Cdc6, Cdt1, Mcm2 and Geminin expression.…”

Section: Discussionmentioning

confidence: 99%

DNA replication licensing in somatic and germ cells

Eward

Obermann

Shreeram

et al. 2004

Journal of Cell Science

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The DNA replication (or origin) licensing system ensures precise duplication of the genome in each cell cycle and is a powerful regulator of cell proliferation in metazoa. Studies in yeast, Drosophila melanogaster and Xenopus laevis have characterised the molecular machinery that constitutes the licensing system, but it remains to be determined how this important evolutionary conserved pathway is regulated in Homo sapiens. We have investigated regulation of the origin licensing factors Cdc6, Cdt1, Mcm2 and Geminin in human somatic and germ cells. Cdc6 and Cdt1 play an essential role in DNA replication initiation by loading the Mcm2-7 complex, which is required for unwinding the DNA helix, onto chromosomal origins. Geminin is a repressor of origin licensing that blocks Mcm2-7 loading onto origins. Our studies demonstrate that Cdc6, Cdt1 and Mcm2 play a central role in coordinating growth during the proliferation-differentiation switch in somatic self-renewing systems and that Cdc6 expression is rate-limiting for acquisition of replication competence in primary oocytes. In striking contrast, we show that proliferation control during male gametogenesis is not linked to Cdc6 or Mcm2, but appears to be coordinated by the negative regulator Geminin with Cdt1 becoming rate-limiting in late prophase. Our data demonstrate a striking sexual dimorphism in the mechanisms repressing origin licensing and preventing untimely DNA synthesis during meiosis I, implicating a pivotal role for Geminin in maintaining integrity of the male germline genome.

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Section: Discussionmentioning

confidence: 99%

DNA replication licensing in somatic and germ cells

Eward

Obermann

Shreeram

et al. 2004

Journal of Cell Science

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“…Although advanced maternal age is the only clearly identified risk factor for chromosomal aneuploidy in the human embryo (Hassold & Hunt 2001, Champion & Hawley 2002, a number of studies have reported particularly high rates of chromosomal aneuploidy and mosaicism in early human IVF embryos (Munne et al 1997, Katz-Jaffe et al 2005, Baart et al 2007. Recently, post-zygotic chromosome instability has been observed to be a common feature of early human embryogenesis, leading to chromosomal disorders such as mosaicism and uniparental disomies in the majority of cleavagestage embryos (Vanneste et al 2009).…”

Section: Does Ovarian Stimulation Disrupt Chromosomal Competence Of Tmentioning

confidence: 99%

The impact of ovarian stimulation for IVF on the developing embryo

Santos¹,

Kuijk²,

Macklon³

2010

Reproduction

175

128

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The use of assisted reproductive technologies (ART) has been increasing over the past three decades, and, in developed countries, ART account for 1-3% of annual births. In an attempt to compensate for inefficiencies in IVF procedures, patients undergo ovarian stimulation using high doses of exogenous gonadotrophins to allow retrieval of multiple oocytes in a single cycle. Although ovarian stimulation has an important role in ART, it may also have detrimental effects on oogenesis, embryo quality, endometrial receptivity and perinatal outcomes. In this review, we consider the evidence for these effects and address possible underlying mechanisms. We conclude that such mechanisms are still poorly understood, and further knowledge is needed in order to increase the safety of ovarian stimulation and to reduce potential effects on embryo development and implantation, which will ultimately be translated into increased pregnancy rates and healthy offspring.

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“…That said, we did not observe a delay in the onset of meiosis in BaxK/K oocytes when compared with WT oocytes. Based on the expression of the markers SCP3, which is involved in the formation and stability of the synaptonemal complex produced during zygotene and pachytene of prophase I (reviewed in Champion & Hawley 2002) and DMC1, which is a germ cell-specific protein involved in DNA repair during recombination (Pittman et al 1998, Yoshida et al 1998, BaxK/K germ cells entered meiosis at an appropriate time.…”

Section: Effect Of Bax Deletion On Oogonia Proliferationmentioning

confidence: 99%

BAX regulates follicular endowment in mice

et al. 2007

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It is believed that the endowment of primordial follicles in mammalian ovaries is finite. Once follicles are depleted, infertility ensues. Thus, the size of the initial endowment has consequences for fertility and reproductive longevity. Follicular endowment is comprised of various processes that culminate with the incorporation of meiosis-arrested oocytes into primordial follicles. Apoptosis is prominent during follicular endowment, and apoptosis regulatory genes are involved in its regulation. Conflicting data exist with regard to the role of the proapoptotic Bcl-2 associated X protein (BAX) in follicular endowment. Therefore, we investigated the role of BAX during follicular endowment in embryonic and neonatal ovaries. We found that BAX is involved in regulating follicular endowment in mice. Deletion of Bax yields increased oocyte numbers in embryonic ovaries and increased follicle numbers in neonatal ovaries when compared with wild-type ovaries. Increased follicular endowment in BaxK/K ovaries is not due to enhanced germ cell viability. Further, it is not due to an increased primordial germ cell (PGC) allotment, a delay in the onset of meiosis, or altered proliferative activity of oogonia. Instead, our data suggest that the regulatory activity of BAX in follicular endowment likely occurs during PGC migration, prior to PGC colonization of the gonad.

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Playing for half the deck: the molecular biology of meiosis

Cited by 28 publications

References 78 publications

DNA replication licensing in somatic and germ cells

DNA replication licensing in somatic and germ cells

The impact of ovarian stimulation for IVF on the developing embryo

BAX regulates follicular endowment in mice

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