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12 - Chromosome behavior and spindle formation in mammalian oocytes

from Section 3 - Developmental biology

Published online by Cambridge University Press:  05 October 2013

By
Heide Schatten  and
Sun Qing-Yuan
Edited by
Alan Trounson ,
Roger Gosden  and
Ursula Eichenlaub-Ritter
Heide Schatten
Affiliation:
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO, USA
Sun Qing-Yuan
Affiliation:
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China
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

Abstract

The formation of the meiotic spindle is a critical process to assure accurate chromosome segregation and subsequent embryo development. Coordinated formation and organization of microtubules, centrosomes, and chromosomes is important for meiotic spindle formation at the oocyte's center after germinal vesicle breakdown (GVBD), for the formation of the MI (meiosis I) spindle to segregate homologous chromosomes, and for the formation of the MII (meiosis II) spindle to segregate chromatids, resulting in oocyte haploidy. The human oocyte is particularly susceptible to errors in chromosome segregation which may be related to defective centrosome and microtubule organization and to defective chromosome attachment to kinetochore microtubules and loss of molecular surveillance factors. The present chapter is focused on (1) formation of central, MI and MII spindle, with focus on microtubules and centrosomes; (2) chromosome dynamics and segregation during MI and MII, with focus on molecular aspects and surveillance mechanisms; and (3) spindle abnormalities, environmental influences, and possible treatments to restore spindle integrity with implications for assisted reproductive technologies (ART).

Introduction

The formation of the meiotic spindle is a critical step during oocyte maturation and begins when the germinal vesicle breaks down (GVBD) as a result of stimulation by luteinizing hormone (LH). Spindle formation in most mammalian oocytes takes place at the oocyte's center and involves significant restructuring of the cytoskeleton that will impact subsequent cellular and molecular functions that are also important for later development [1]. Coordinated formation and organization of microtubules, centrosomes, and chromosomes begins directly after GVBD with remodeling of these major spindle components in the oocyte's center to form the meiotic spindle.

Type
Chapter
Information
Biology and Pathology of the Oocyte
Role in Fertility, Medicine and Nuclear Reprograming
 , pp. 142 - 153
Publisher: Cambridge University Press
Print publication year: 2013

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References

Sirard, MA, Richard, F, Blondin, P, Robert, C. Contribution of the oocyte to embryo quality. Theriogenology 2006; 65: 126–36.CrossRefGoogle ScholarPubMed
Pellestor, F, Anahory, T, Hamamah, S. Effect of maternal age on the frequency of cytogenetic abnormalities in human oocytes. Cytogenet Genome Res 2005; 111: 206–12.CrossRefGoogle ScholarPubMed
Hassold, T, Hunt, P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2001; 2: 280–91.CrossRefGoogle Scholar
Kuliev, A, Cieslak, J, Verlinsky, Y. Frequency and distribution of chromosome abnormalities in human oocytes. Cytogenet Genome Res 2005; 111: 193–8.CrossRefGoogle ScholarPubMed
Rosenbusch, BE, Schneider, M. Cytogenetic analysis of human oocytes remaining unfertilized after intracytoplasmic sperm injection. Fertil Steril 2006; 85: 302–7.CrossRefGoogle ScholarPubMed
Pacchierotti, F, Ranaldi, R, Eichenlaub-Ritter, U, Attia, S, Adler, ID. Evaluation of aneugenic effects of bisphenol A in somatic and germ cells of the mouse. Mutat Res 2008; 651(1–2): 64–70.CrossRefGoogle ScholarPubMed
Kuliev, A, Zlatopolsky, Z, Kirillova, I, Spivakova, J, Cieslak, Janzen J. Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reprod Biomed Online 2011; 22(1): 2–8.CrossRefGoogle ScholarPubMed
Eichenlaub-Ritter, U, Stahl, A, Luciani, J M. The microtubular cytoskeleton and chromosomes of unfertilized human oocytes aged in vitro. Hum Genet 1988; 80: 259–64.CrossRefGoogle ScholarPubMed
Eichenlaub-Ritter, U. Genetics of oocyte aging. Maturitas 1998; 30: 143–69.CrossRefGoogle Scholar
Miao, Y-L, Kikuchi, K, Sun, Q-Y, Schatten, H. Oocyte aging: cellular and molecular changes, developmental potential and reversal possibility. Hum Reprod Update 2009; 15(5): 573–85.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, QY. The role of centrosomes in mammalian fertilization and its significance for ICSI. Mol Hum Reprod 2009; 15(9): 531–8.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, Q-Y. Centrosome dynamics during meiotic spindle formation in oocyte maturation. Mol. Reprod. Develop 2011; 78: 757–68.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, Q-Y. New insights into the role of centrosomes in mammalian fertilisation and implications for ART. Reproduction 2011; 142: 793–801.CrossRefGoogle ScholarPubMed
Jones, KT. Meiosis in oocytes: predisposition to aneuploidy and its increased incidence with age. Hum Reprod Update 2008; 14(2): 143–58.CrossRefGoogle ScholarPubMed
Holt, JE, Jones, KT. Control of homologous chromosome division in the mammalian oocyte. Mol Hum Reprod 2009; 15(3): 139–47.CrossRefGoogle ScholarPubMed
Wang, Z-B, Schatten, H, Sun, Q-Y. Why is chromosome segregation error in oocytes increased with maternal aging?Physiology 2011; 26(5): 314–25.CrossRefGoogle ScholarPubMed
Swain, JE, Pool, TB. ART failure: oocyte contributions to unsuccessful fertilization. Hum Reprod Update 2008; 14(5): 431–46.CrossRefGoogle ScholarPubMed
Ai, J-S, Li, M, Schatten, H, Sun, Q-Y. Regulatory mechanism of spindle movements during oocyte meiotic division. Asian Aust J Anim Sci 2009; 22: 1447–86.CrossRefGoogle Scholar
Fan, H-Y, Liu, Z, Shimada, M, et al. MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science 2009; 324: 938–41.CrossRefGoogle ScholarPubMed
Gosden, R, Lee, B. Portrait of an oocyte: our obscure origin. J Clin Invest 2010; 120(4): 973–83.CrossRefGoogle ScholarPubMed
Brunet, S, Verlhac, MH. Positioning to get out of meiosis: the asymmetry of division. Hum Reprod Update 2011; 17(1): 68–75.CrossRefGoogle ScholarPubMed
Stearns, T. The tubulin superfamily. In: Nigg, E, ed. Centrosomes in Development and Disease. Weinheim: Wiley-VCA Verlag GmbH & CoKGaG. 2004; 17–25.Google Scholar
Moritz, M, Rice, LM, Agard, DA. Microtubule nucleation. In: Nigg, E, ed. Centrosomes in Development and Disease. Weinheim: Wiley-VCA Verlag GmbH & CoKGaG. 2004; 27–41.Google Scholar
Doxsey, SJ, Stein, P, Evans, L, Calarco, P, Kirschner, M. Pericentrin, a highly conserved protein of centrosomes involved in microtubule organization. Cell 1994; 76: 639–50.CrossRefGoogle ScholarPubMed
Dictenberg, J, Zimmerman, W, Sparks, C, et al. Pericentrin and gamma-tubulin form a protein complex and are organized into a novel lattice at the centrosome. J Cell Biol 1998; 141: 163–74.CrossRefGoogle Scholar
Young, A, Dictenberg, JB, Purohit, A, Tuft, R, Doxsey, SJCytoplasmic dynein-mediated assembly of pericentrin and γ-tubulin onto centrosomes. Mol Biol Cell 2000; 11: 2047–56CrossRefGoogle ScholarPubMed
Sun, QY, Schatten, H. Multiple roles of NuMA in vertebrate cells: review of an intriguing multi-functional protein. Front Biosci 2006; 11: 1137–46.CrossRefGoogle Scholar
Alvarez, Sedó CA, Schatten, H, Combelles, C, Rawe, VY. The nuclear mitotic apparatus protein NuMA: localization and dynamics in human oocytes, fertilization and early embryos. Mol Hum Reprod 2011; 17(6): 392–8.Google Scholar
Schatten, H, Rawe, VY, Sun, QY. Cytoskeletal architecture of human oocytes with focus on centrosomes and their significant role in fertilization. In: Nagy, ZP, Varghese, A, Agarwal, A, eds. Practical Manual of In Vitro Fertilization: Advanced Methods and Novel Devices. New York: Springer. 2012; 667–76.CrossRefGoogle Scholar
Schatten, H. The mammalian centrosome and its functional significance. Histochem Cell Biol 2008; 129: 667–86.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, QY. The role of centrosomes in fertilization, cell division and establishment of asymmetry during embryo development. Semin Cell Dev Biol 2010; 21: 174–84.CrossRefGoogle ScholarPubMed
Schatten, G, Simerly, C, Schatten, H. Microtubule configurations during fertilization, mitosis and early development in the mouse and the requirement for egg microtubule-mediated motility during mammalian fertilization. Proc Natl Acad Sci USA 1985; 82: 4152–6.CrossRefGoogle ScholarPubMed
Schatten, H, Schatten, G, Mazia, D, Balczon, R, Simerly, C. Behavior of centrosomes during fertilization and cell division in mouse oocytes and in sea urchin eggs. Proc Natl Acad Sci USA 1986; 83: 105–9.CrossRefGoogle ScholarPubMed
Maro, B, Howlett, SK, Webb, M. Non-spindle microtubule organizing centers in metaphase II-arrested mouse oocytes. J Cell Biol 1985; 101: 1665–72.CrossRefGoogle ScholarPubMed
Schuh, M, Ellenberg, J. Self-organization of MTOCs replaces centrosome function during acentrosomal spindle assembly in live mouse oocytes. Cell 2007; 130: 484–98.CrossRefGoogle ScholarPubMed
Kim, N-H, Funahashi, H, Prather, RS, Schatten, G, Day, BN. Microtubule and microfilament dynamics in porcine oocytes during meiotic maturation. Mol Reprod Dev 1996; 43: 248–55.3.0.CO;2-#>CrossRefGoogle ScholarPubMed
Le Guen, P, Crozet, N. Microtubule and centrosome distribution during sheep fertilization. Eur J Cell Biol 1989; 48: 239–49.Google ScholarPubMed
Long, CR, Pinto-Correia, C, Duby, RT, et al. Chromatin and microtubule morphology during the first cell cycle in bovine zygotes. Mol Reprod Dev 1993; 36: 23–32.CrossRefGoogle ScholarPubMed
Gueth-Hallonet, C, Antony, C, Aghion, J, et al. γ-Tubulin is present in acentriolar MTOCs during early mouse development. J Cell Sci 1993; 105: 157–66.Google ScholarPubMed
Lee, J, Miyano, T, Moor, RM. Spindle formation and dynamics of γ-tubulin and nuclear mitotic apparatus protein distribution during meiosis in pig and mouse oocytes. Biol Reprod 2000; 62: 1184–92.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, QY. The functional significance of centrosomes in mammalian meiosis, fertilization, development, nuclear transfer, and stem cell differentiation. Environ Mol Mutagen 2009; 50(8): 620–36.CrossRefGoogle ScholarPubMed
Schatten, H, Sun, Q-Y. The significant role of centrosomes in stem cell division and differentiation. Microsc Microanal 2011; 17(4): 506–12.CrossRefGoogle Scholar
Can, A, Semiz, O, Çinar, O. Centrosome and microtubule dynamics during early stages of meiosis in mouse oocytes. Mol Hum Reprod 2003; 9(12): 749–56.CrossRefGoogle ScholarPubMed
Brunet, S, Maro, B. Cytoskeleton and cell cycle control during meiotic maturation of the mouse oocyte: integrating time and space. Reproduction 2005; 130: 801–11.CrossRefGoogle ScholarPubMed
Ai, J-S, Wang, Q, Li, M, et al. Roles of microtubules and microfilaments in spindle movements during rat oocyte meiosis. J Reprod Dev 2008; 54: 391–6.CrossRefGoogle ScholarPubMed
Ai, J-S, Wang, Q, Yin, S, et al. Regulation of peripheral spindle movement and spindle rotation during mouse oocyte meiosis: new perspectives. Microsc Microanal 2008; 14(4): 349–56.CrossRefGoogle ScholarPubMed
Fan, HY, Huo, LJ, Meng, XQ, et al. Involvement of calcium/calmodulin-dependent protein kinase II (CaMKII) in meiotic maturation and activation of pig oocytes. Biol Reprod 2003; 69: 1552–64.CrossRefGoogle ScholarPubMed
Messinger, SM, Albertini, DF. Centrosome and microtubule dynamics during meiotic progression in the mouse oocyte. J Cell Sci 1991; 100: 289–98.Google ScholarPubMed
Combelles, CM, Albertini, DF. Microtubule patterning during meiotic maturation in mouse oocytes is determined by cell cycle-specific sorting and redistribution of gamma-tubulin. Dev Biol 2001; 239: 281–94.CrossRefGoogle ScholarPubMed
Sanfins, A, Plancha, CE, Overstrom, EW, Albertini, DF. Meiotic spindle morphogenesis in in vivo and in vitro matured mouse oocytes: insights into the relationship between nuclear and cytoplasmic quality. Hum Reprod 2004; 19(12): 2889–99.CrossRefGoogle ScholarPubMed
Fan, HY, Sun, QY. Involvement of mitogen-activated protein kinase cascade during oocyte maturation and fertilization in mammals. Biol Reprod 2004; 70: 535–47.CrossRefGoogle ScholarPubMed
Yu, LZ, Xiong, B, Gao, WX, et al. MEK1/2 regulates microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte meiotic maturation. Cell Cycle 2007; 6: 330–8.CrossRefGoogle ScholarPubMed
Kubiak, JZ, Weber, M, Geraud, G, Maro, B. Cell cycle modification during the transitions between meiotic M-phases in mouse oocytes. J Cell Sci 1992; 102: 457–67.Google ScholarPubMed
Hampl, A, Eppig, JJ. Analysis of the mechanism(s) of metaphase I arrest in maturing mouse oocytes. Development 1995; 121: 925–33.Google ScholarPubMed
Sun, QY, Lai, L, Wu, G, et al. Regulation of mitogen-activated protein kinase phosphorylation, microtubule organization, chromatin behavior, and cell cycle progression are regulated by protein phosphatases during pig oocyte maturation and fertilization in vitro. Biol Reprod 2002; 66(3): 580–8.CrossRefGoogle Scholar
Yin, S, Sun, X-F, Schatten, H, Sun, Q-Y. Molecular insights into mechanisms regulating faithful chromosome separation in female meiosis. Cell Cycle 2008; 7(19): 2997–3005.CrossRefGoogle ScholarPubMed
Szollosi, D, Calarco, P, Donahue, RP. Absence of centrioles in the first and second meiotic spindles of mouse oocytes. J Cell Sci 1972; 11: 521–41.Google ScholarPubMed
Calarco-Gillam, PC, Siebert, MC, Hubble, R, Mitchison, T, Kirschner, M. Centrosome development in early mouse embryos as defined by an autoantibody against pericentriolar material. Cell 1983; 35(3 Pt 2): 621–9.CrossRefGoogle ScholarPubMed
Dumont, J, Petri, S, Pellegrin, F, et al. A centriole- and RanGTP-independent spindle assembly pathway in meiosis I of vertebrate oocytes. J Cell Biol 2007; 176: 295–305.CrossRefGoogle ScholarPubMed
Moritz, M, Braunfeld, MB, Sedat, JW, Alberts, B, Agard, DAMicrotubule nucleation by gamma-tubulin-containing rings in the centrosome. Nature 1995; 378: 638–40.CrossRefGoogle ScholarPubMed
Zheng, Y, Wong, ML, Alberts, B, Mitchison, T. Nucleation of microtubule assembly by a gamma-tubulin-containing ring complex. Nature 1995; 378: 578–83.CrossRefGoogle ScholarPubMed
Kitajima, TS, Ohsugi, M, Ellenberg, J. Complete kinetochore tracking reveals error-prone homologous chromosome biorientation in mammalian oocytes. Cell 2011; 146(4): 568–81.CrossRefGoogle ScholarPubMed
Zhang, Q-H, Wei, L, Tong, J-S, et al. Localization and function of Spindly during mouse oocyte meiotic maturation. Cell Cycle 2010; 9(11): 2230–6.CrossRefGoogle ScholarPubMed
Schatten, H, Walter, M, Biessmann, H, Schatten, G. Activation of maternal centrosomes in unfertilized sea urchin eggs. Cell Motil Cytoskel 1992; 23: 61–70.CrossRefGoogle ScholarPubMed
Leibfried-Rutledge, ML, Critser, ES, Eyestone, WH, Northey, DL, First, NL. Development potential of bovine oocytes matured in vitro and in vivo. Biol Reprod 1987; 36: 376–83.CrossRefGoogle Scholar
Liu, H, Krey, LC, Zhang, J, Grifo, JA. Ooplasmic influence on nuclear function during the metaphase II-interphase transition in mouse oocytes. Biol Reprod 2001; 65: 1794–9.CrossRefGoogle ScholarPubMed
Trounson, A, Anderiesz, C, Jones, G. Maturation of human oocytes in vitro and their developmental competence. Reproduction 2001; 121: 51–75.CrossRefGoogle ScholarPubMed
Combelles, CM, Cekleniak, NA, Racowsky, C, Albertini, DF. Assessment of nuclear and cytoplasmic maturation in in vitro matured human oocytes. Hum Reprod 2002; 17: 1006–16.CrossRefGoogle ScholarPubMed
MacQueen, AJ, Hochwagen, A. Checkpoint mechanisms: the puppet masters of meiotic prophase. Trends Cell Biol 2011; 21: 393–400.CrossRefGoogle ScholarPubMed
Zickler, D. From early homologue recognition to synaptonemal complex formation. Chromosoma 2006; 115: 158–74.CrossRefGoogle ScholarPubMed
Battaglia, DE, Goodwin, P, Klein, NA, Soules, MR. Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women. Hum Reprod 1996; 11: 2217–22.CrossRefGoogle ScholarPubMed
Garcia-Cruz, R, Brieno, MA, Roig, I, et al. Dynamics of cohesin proteins REC8, STAG3, SMC1 beta and SMC3 are consistent with a role in sister chromatid cohesion during meiosis in human oocytes. Hum Reprod 2010; 25: 2316–27.CrossRefGoogle ScholarPubMed
Prieto, I, Tease, C, Pezzi, N, et al. Cohesin component dynamics during meiotic prophase I in mammalian oocytes. Chromosome Res 2004; 12: 197–213.CrossRefGoogle ScholarPubMed
Revenkova, E, Jessberger, R. Keeping sister chromatids together: cohesins in meiosis. Reproduction 2005; 130: 783–90.CrossRefGoogle ScholarPubMed
Terret, ME, Wassmann, K, Waizenegger, I, et al. The meiosis I-to-meiosis II transition in mouse oocytes requires separase activity. Curr Biol 2003; 13: 1797–802.CrossRefGoogle ScholarPubMed
Kudo, NR, Wassmann, K, Anger, M, et al. Resolution of chiasmata in oocytes requires separase-mediated proteolysis. Cell 2006; 126: 135–46.CrossRefGoogle ScholarPubMed
Sun, SC, Kim, NH. Spindle assembly checkpoint and its regulators in meiosis. Hum Reprod Update 2012; 18(1): 60–72.CrossRefGoogle ScholarPubMed
Vogt, E, Sanhaji, M, Klein, W, et al. MCAK is present at centromeres, midspindle and chiasmata and involved in silencing of the spindle assembly checkpoint in mammalian oocytes. Mol Hum Reprod 2010; 16(9): 665–84.CrossRefGoogle ScholarPubMed
Maiato, H, DeLuca, J, Salmon, ED, Earnshaw, WC. The dynamic kinetochore-microtubule interface. J Cell Sci 2004; 117: 5461–77.CrossRefGoogle ScholarPubMed
Kolano, A, Brunet, S, Silk, AD, Cleveland, DW, Verlhac, MH. Error-prone mammalian female meiosis from silencing the spindle assembly checkpoint without normal interkinetochore tension. Proc Natl Acad Sci USA 2012; 109(27): E1858–67.CrossRefGoogle ScholarPubMed
Speroff, L. The effect of aging on fertility. Curr Opin Obstet Gynecol 1994; 6: 115–20.CrossRefGoogle ScholarPubMed
Eichenlaub-Ritter, U, Chandley, AC, Gosden, RG. Alterations to the microtubular cytoskeleton and increased disorder of chromosome alignment in spontaneously ovulated mouse oocytes aged in vivo: an immunofluorescence study. Chromosoma 1986; 94: 337–45.CrossRefGoogle ScholarPubMed
Hornak, M, Jeseta, M, Musilova, P, et al. Frequency of aneuploidy related to age in porcine oocytes. PLoS One 2011; 6(4): e18892.CrossRefGoogle ScholarPubMed
Miao, Y-L, Sun, Q-Y, Zhang, X, et al. Centrosome abnormalities during porcine oocyte aging. Environ Mol Mutagen 2009; 50(8): 666–71.
Eichenlaub-Ritter, U, Vogt, E, Cukurcam, S, et al. Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy. Mutat Res 2008; 651: 82–92.CrossRefGoogle Scholar

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