Oogenesis pp 253-264 | Cite as

Oocyte Polarity and Its Developmental Significance

  • Anna AjdukEmail author
  • Agnieszka Jedrusik
  • Magdalena Zernicka-Goetz


Establishment of the animal-vegetal (AV) axis is one of the most important events of meiotic maturation in mammalian oocytes, as it extensively affects further embryonic development. Initially, in prophase of the first meiotic division (ProI), an oocyte is radially symmetric, with a nucleus localized in the cell centre. After resumption of meiosis, metaphase I (MetI) spindle is moved from the central position towards the cortex, marking an animal pole of the oocyte. Translocation of the meiotic spindle depends on actin cytoskeleton and leads to an extensive reorganization of the animal cortex, an event regulated by complex molecular pathways. Asymmetric localization of the oocyte chromatin is maintained in the metaphase II (Met II) stage. Migration of the spindle to the cortex ensures that both meiotic divisions occur in an asymmetric manner giving rise to small polar bodies and the big egg cell containing most of the maternal factors stored during oogenesis. Moreover, cortical reorganization caused by translocation of the oocyte chromatin prevents egg-sperm fusion in the vicinity of the animal pole and in consequence precocious mixing of maternal and paternal chromosomes that could disturb proper segregation of genetic material during the second meiotic division. Finally, recent research provides evidence that the AV axis formed in the oocyte may influence embryonic fate of the blastomeres, as cells containing either animal or vegetal components are differentially predisposed. We would like to present here the current stage of knowledge regarding molecular mechanism of AV axis formation in mammalian oocytes and developmental significance of this process.


Mammalian oocyte Mouse Polarity Actin Spindle Microvilli Meiosis Fertilization Animal/vegetal axis Developmental potential 


  1. 1.
    Longo FJ, Chen DY. Development of cortical polarity in mouse eggs: involvement of the meiotic apparatus. Dev Biol. 1985;107:382–94.PubMedCrossRefGoogle Scholar
  2. 2.
    Li H, Guo F, Rubinstein B, Li R. Actin-driven chromosomal motility leads to symmetry breaking in mammalian meiotic oocytes. Nat Cell Biol. 2008;10:1301–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Schuh M, Ellenberg J. A new model for asymmetric spindle positioning in mouse oocytes. Curr Biol. 2008;18:1986–92.PubMedCrossRefGoogle Scholar
  4. 4.
    Azoury J, Lee KW, Georget V, Rassinier P, Leader B, et al. Spindle positioning in mouse oocytes relies on a dynamic meshwork of actin filaments. Curr Biol. 2008;18:1514–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Na J, Zernicka-Goetz M. Asymmetric positioning and organization of the meiotic spindle of mouse oocytes requires CDC42 function. Curr Biol. 2006;16:1249–54.PubMedCrossRefGoogle Scholar
  6. 6.
    Dumont J, Million K, Sunderland K, Rassinier P, Lim H, et al. Formin-2 is required for spindle migration and for the late steps of cytokinesis in mouse oocytes. Dev Biol. 2007;301:254–65.PubMedCrossRefGoogle Scholar
  7. 7.
    Leader B, Lim H, Carabatsos MJ, Harrington A, Ecsedy J, et al. Formin-2, polyploidy, hypofertility and positioning of the meiotic spindle in mouse oocytes. Nat Cell Biol. 2002;4:921–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Duncan FE, Moss SB, Schultz RM, Williams CJ. PAR-3 defines a central subdomain of the cortical actin cap in mouse eggs. Dev Biol. 2005;280:38–47.PubMedCrossRefGoogle Scholar
  9. 9.
    Vinot S, Le T, Maro B, Louvet-Vallee S. Two PAR6 proteins become asymmetrically localized during establishment of polarity in mouse oocytes. Curr Biol. 2004;14:520–5.PubMedCrossRefGoogle Scholar
  10. 10.
    Gray D, Plusa B, Piotrowska K, Na J, Tom B, et al. First cleavage of the mouse embryo responds to change in egg shape at fertilization. Curr Biol. 2004;14:397–405.PubMedCrossRefGoogle Scholar
  11. 11.
    Insolera R, Chen S, Shi SH. Par proteins and neuronal polarity. Dev Neurobiol. 2011;71:483–94.PubMedCrossRefGoogle Scholar
  12. 12.
    Ohno S. Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr Opin Cell Biol. 2001;13:641–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Yanagimachi R. Sperm-egg association in animals. Curr Top Dev Biol. 1978;12:83–105.PubMedCrossRefGoogle Scholar
  14. 14.
    Nicosia SV, Wolf DP, Inoue M. Cortical granule distribution and cell surface characteristics in mouse eggs. Dev Biol. 1977;57:56–74.PubMedCrossRefGoogle Scholar
  15. 15.
    Wilson NF, Snell WJ. Microvilli and cell-cell fusion during fertilization. Trends Cell Biol. 1998;8:93–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Pfender S, Kuznetsov V, Pleiser S, Kerkhoff E, Schuh M. Spire-type actin nucleators cooperate with Formin-2 to drive asymmetric oocyte division. Curr Biol. 2011;21:955–60.PubMedCrossRefGoogle Scholar
  17. 17.
    Sun SC, Wang ZB, Xu YN, Lee SE, Cui XS, et al. Arp2/3 complex regulates asymmetric division and cytokinesis in mouse oocytes. PLoS One. 2011;6:e18392.PubMedCrossRefGoogle Scholar
  18. 18.
    Sun SC, Sun QY, Kim NH. JMY is required for asymmetric division and cytokinesis in mouse oocytes. Mol Hum Reprod. (2011) 17:296–304.Google Scholar
  19. 19.
    Sun SC, Xu YN, Li YH, Lee SE, Jin YX, et al. WAVE2 regulates meiotic spindle stability, peripheral positioning and polar body emission in mouse oocytes. Cell Cycle. 2011;10:1853–60.PubMedCrossRefGoogle Scholar
  20. 20.
    Bielak-Zmijewska A, Kolano A, Szczepanska K, Maleszewski M, Borsuk E. Cdc42 protein acts upstream of IQGAP1 and regulates cytokinesis in mouse oocytes and embryos. Dev Biol. 2008;322:21–32.PubMedCrossRefGoogle Scholar
  21. 21.
    Simerly C, Nowak G, de Lanerolle P, Schatten G. Differential expression and functions of cortical myosin IIA and IIB isotypes during meiotic maturation, fertilization, and mitosis in mouse oocytes and embryos. Mol Biol Cell. 1998;9:2509–25.PubMedGoogle Scholar
  22. 22.
    Azoury J, Lee KW, Georget V, Hikal P, Verlhac MH. Symmetry breaking in mouse oocytes requires transient F-actin meshwork destabilization. Development. 2011;138:2903–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Deng M, Suraneni P, Schultz RM, Li R. The Ran GTPase mediates chromatin signaling to control cortical polarity during polar body extrusion in mouse oocytes. Dev Cell. 2007;12:301–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Araki K, Naito K, Haraguchi S, Suzuki R, Yokoyama M, et al. Meiotic abnormalities of c-mos knockout mouse oocytes: activation after first meiosis or entrance into third meiotic metaphase. Biol Reprod. 1996;55:1315–24.PubMedCrossRefGoogle Scholar
  25. 25.
    Verlhac MH, Lefebvre C, Guillaud P, Rassinier P, Maro B. Asymmetric division in mouse oocytes: with or without Mos. Curr Biol. 2000;10:1303–6.PubMedCrossRefGoogle Scholar
  26. 26.
    Deng M, Williams CJ, Schultz RM. Role of MAP kinase and myosin light chain kinase in chromosome-induced development of mouse egg polarity. Dev Biol. 2005;278:358–66.PubMedCrossRefGoogle Scholar
  27. 27.
    Choi T, Fukasawa K, Zhou R, Tessarollo L, Borror K, et al. The Mos/mitogen-activated protein kinase (MAPK) pathway regulates the size and degradation of the first polar body in maturing mouse oocytes. Proc Natl Acad Sci USA. 1996;93:7032–5.PubMedCrossRefGoogle Scholar
  28. 28.
    Yu LZ, Xiong B, Gao WX, Wang CM, Zhong ZS, et al. MEK1/2 regulates microtubule organization, spindle pole tethering and asymmetric division during mouse oocyte meiotic maturation. Cell Cycle. 2007;6:330–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Tong C, Fan HY, Chen DY, Song XF, Schatten H, et al. Effects of MEK inhibitor U0126 on meiotic progression in mouse oocytes: microtubule organization, asymmetric division and metaphase II arrest. Cell Res. 2003;13:375–83.PubMedCrossRefGoogle Scholar
  30. 30.
    Deng M, Kishikawa H, Yanagimachi R, Kopf GS, Schultz RM, et al. Chromatin-mediated cortical granule redistribution is responsible for the formation of the cortical granule-free domain in mouse eggs. Dev Biol. 2003;257:166–76.PubMedCrossRefGoogle Scholar
  31. 31.
    Ducibella T, Kurasawa S, Rangarajan S, Kopf GS, Schultz RM. Precocious loss of cortical granules during mouse oocyte meiotic maturation and correlation with an egg-induced modification of the zona pellucida. Dev Biol. 1990;137:46–55.PubMedCrossRefGoogle Scholar
  32. 32.
    Okada A, Yanagimachi R, Yanagimachi H. Development of a cortical granule-free area of cortex and the perivitelline space in the hamster oocyte during maturation and following ovulation. J Submicrosc Cytol. 1986;18:233–47.PubMedGoogle Scholar
  33. 33.
    Ducibella T, Anderson E, Albertini DF, Aalberg J, Rangarajan S. Quantitative studies of changes in cortical granule number and distribution in the mouse oocyte during meiotic maturation. Dev Biol. 1988;130:184–97.PubMedCrossRefGoogle Scholar
  34. 34.
    Maro B, Johnson MH, Pickering SJ, Flach G. Changes in actin distribution during fertilization of the mouse egg. J Embryol Exp Morphol. 1984;81:211–37.PubMedGoogle Scholar
  35. 35.
    Halet G, Carroll J. Rac activity is polarized and regulates meiotic spindle stability and anchoring in mammalian oocytes. Dev Cell. 2007;12:309–17.PubMedCrossRefGoogle Scholar
  36. 36.
    Derivery E, Gautreau A. Generation of branched actin networks: assembly and regulation of the N-WASP and WAVE molecular machines. Bioessays. 2010;32:119–31.PubMedCrossRefGoogle Scholar
  37. 37.
    Yi K, Unruh JR, Deng M, Slaughter BD, Rubinstein B, et al. Dynamic maintenance of asymmetric meiotic spindle position through Arp2/3-complex-driven cytoplasmic streaming in mouse oocytes. Nat Cell Biol. 2011;13:1252–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Shalgi R, Phillips DM. Mechanics of in vitro fertilization in the hamster. Biol Reprod. 1980;23:433–44.PubMedCrossRefGoogle Scholar
  39. 39.
    Yanagimachi R, Noda YD. Electron microscope studies of sperm incorporation into the golden hamster egg. Am J Anat. 1970;128:429–62.PubMedCrossRefGoogle Scholar
  40. 40.
    Evans JP, Foster JA, McAvey BA, Gerton GL, Kopf GS, et al. Effects of perturbation of cell polarity on molecular markers of sperm-egg binding sites on mouse eggs. Biol Reprod. 2000;62:76–84.PubMedCrossRefGoogle Scholar
  41. 41.
    Kaji K, Oda S, Shikano T, Ohnuki T, Uematsu Y, et al. The gamete fusion process is defective in eggs of Cd9-deficient mice. Nat Genet. 2000;24:279–82.PubMedCrossRefGoogle Scholar
  42. 42.
    Le Naour F, Rubinstein E, Jasmin C, Prenant M, Boucheix C. Severely reduced female fertility in CD9-deficient mice. Science. 2000;287:319–21.PubMedCrossRefGoogle Scholar
  43. 43.
    Miyado K, Yamada G, Yamada S, Hasuwa H, Nakamura Y, et al. Requirement of CD9 on the egg plasma membrane for fertilization. Science. 2000;287:321–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Runge KE, Evans JE, He ZY, Gupta S, McDonald KL, et al. Oocyte CD9 is enriched on the microvillar membrane and required for normal microvillar shape and distribution. Dev Biol. 2007;304:317–25.PubMedCrossRefGoogle Scholar
  45. 45.
    Komorowski S, Szczepanska K, Maleszewski M. Distinct mechanisms underlie sperm-induced and protease-induced oolemma block to sperm penetration. Int J Dev Biol. 2003;47:65–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Ephrussi A, St Johnston D. Seeing is believing: the bicoid morphogen gradient matures. Cell. 2004;116:143–52.PubMedCrossRefGoogle Scholar
  47. 47.
    Gurdon JB. The generation of diversity and pattern in animal development. Cell. 1992;68:185–99.PubMedCrossRefGoogle Scholar
  48. 48.
    Kloc M, Bilinski S, Chan AP, Allen LH, Zearfoss NR, et al. RNA localization and germ cell determination in Xenopus. Int Rev Cytol. 2001;203:63–91.PubMedCrossRefGoogle Scholar
  49. 49.
    Rossant J. Postimplantation development of blastomeres isolated from 4- and 8-cell mouse eggs. J Embryol Exp Morphol. 1976;36:283–90.PubMedGoogle Scholar
  50. 50.
    Tarkowski AK. Experiments on the development of isolated blastomeres of mouse eggs. Nature. 1959;184:1286–7.PubMedCrossRefGoogle Scholar
  51. 51.
    Tarkowski AK. Mouse chimaeras developed from fused eggs. Nature. 1961;190:857–60.PubMedCrossRefGoogle Scholar
  52. 52.
    Tarkowski AK, Wroblewska J. Development of blastomeres of mouse eggs isolated at the 4- and 8-cell stage. J Embryol Exp Morphol. 1967;18:155–80.PubMedGoogle Scholar
  53. 53.
    Tsunoda Y, McLaren A. Effect of various procedures on the viability of mouse embryos containing half the normal number of blastomeres. J Reprod Fertil. 1983;69:315–22.PubMedCrossRefGoogle Scholar
  54. 54.
    Gardner RL. The early blastocyst is bilaterally symmetrical and its axis of symmetry is aligned with the animal-vegetal axis of the zygote in the mouse. Development. 1997;124:289–301.PubMedGoogle Scholar
  55. 55.
    Zernicka-Goetz M. Fertile offspring derived from mammalian eggs lacking either animal or vegetal poles. Development. 1998;125:4803–8.PubMedGoogle Scholar
  56. 56.
    Plusa B, Grabarek JB, Piotrowska K, Glover DM, Zernicka-Goetz M. Site of the previous meiotic division defines cleavage orientation in the mouse embryo. Nat Cell Biol. 2002;4:811–5.PubMedCrossRefGoogle Scholar
  57. 57.
    Plusa B, Hadjantonakis AK, Gray D, Piotrowska-Nitsche K, Jedrusik A, et al. The first cleavage of the mouse zygote predicts the blastocyst axis. Nature. 2005;434:391–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Bischoff M, Parfitt DE, Zernicka-Goetz M. Formation of the embryonic-abembryonic axis of the mouse blastocyst: relationships between orientation of early cleavage divisions and pattern of symmetric/asymmetric divisions. Development. 2008;135:953–62.PubMedCrossRefGoogle Scholar
  59. 59.
    Fujimori T, Kurotaki Y, Miyazaki J, Nabeshima Y. Analysis of cell lineage in two- and four-cell mouse embryos. Development. 2003;130:5113–22.PubMedCrossRefGoogle Scholar
  60. 60.
    Kurotaki Y, Hatta K, Nakao K, Nabeshima Y, Fujimori T. Blastocyst axis is specified independently of early cell lineage but aligns with the ZP shape. Science. 2007;316:719–23.PubMedCrossRefGoogle Scholar
  61. 61.
    Piotrowska K, Wianny F, Pedersen RA, Zernicka-Goetz M. Blastomeres arising from the first cleavage division have distinguishable fates in normal mouse development. Development. 2001;128:3739–48.PubMedGoogle Scholar
  62. 62.
    Gardner RL, McLaren A. Cell distribution in chimaeric mouse embryos before implantation. J Embryol Exp Morphol. 1974;32:495–503.Google Scholar
  63. 63.
    Kelly SJ. Investigations into the degree of cell mixing that occurs between the 8-cell stage and the blastocyst stage of mouse development. J Embryol Exp Morphol. 1979;207:121–30.Google Scholar
  64. 64.
    Kelly SJ, Mulnard JG, Graham CF. Cell division and cell allocation in early mouse development. J Embryol Exp Morphol. 1978;48:37–51.PubMedGoogle Scholar
  65. 65.
    Motosugi N, Bauer T, Polanski Z, Solter D, Hiiragi T. Polarity of the mouse embryo is established at blastocyst and is not prepatterned. Genes Dev. 2005;19:1081–92.PubMedCrossRefGoogle Scholar
  66. 66.
    Piotrowska-Nitsche K, Zernicka-Goetz M. Spatial arrangement of individual 4-cell stage blastomeres and the order in which they are generated correlate with blastocyst pattern in the mouse embryo. Mech Dev. 2005;122:487–500.PubMedCrossRefGoogle Scholar
  67. 67.
    Howlett SK, Bolton VN. Sequence and regulation of morphological and molecular events during the first cell cycle of mouse embryogenesis. J Embryol Exp Morphol. 1985;87:175–206.PubMedGoogle Scholar
  68. 68.
    Gardner RL. Experimental analysis of second cleavage in the mouse. Hum Reprod. 2002;17:3178–89.PubMedCrossRefGoogle Scholar
  69. 69.
    Piotrowska-Nitsche K, Perea-Gomez A, Haraguchi S, Zernicka-Goetz M. Four-cell stage mouse blastomeres have different developmental properties. Development. 2005;132:479–90.PubMedCrossRefGoogle Scholar
  70. 70.
    Torres-Padilla ME, Parfitt DE, Kouzarides T, Zernicka-Goetz M. Histone arginine methylation regulates pluripotency in the early mouse embryo. Nature. 2007;445:214–8.PubMedCrossRefGoogle Scholar
  71. 71.
    Plachta N, Bollenbach T, Pease S, Fraser SE, Pantazis P. Oct4 kinetics predict cell lineage patterning in the early mammalian embryo. Nat Cell Biol. 2011;13:117–23.PubMedCrossRefGoogle Scholar
  72. 72.
    Jedrusik A, Parfitt DE, Guo G, Skamagki M, Grabarek JB, et al. Role of Cdx2 and cell polarity in cell allocation and specification of trophectoderm and inner cell mass in the mouse embryo. Genes Dev. 2008;22:2692–706.PubMedCrossRefGoogle Scholar
  73. 73.
    Jedrusik A, Bruce AW, Tan MH, Leong DE, Skamagki M, et al. Maternally and zygotically provided Cdx2 have novel and critical roles for early development of the mouse embryo. Dev Biol. 2010;344:66–78.PubMedCrossRefGoogle Scholar
  74. 74.
    Alarcon VB. Cell polarity regulator PARD6B is essential for trophectoderm formation in the preimplantation mouse embryo. Biol Reprod. 2010;83(3):347–58.PubMedCrossRefGoogle Scholar
  75. 75.
    Plusa B, Frankenberg S, Chalmers A, Hadjantonakis AK, Moore CA, et al. Downregulation of Par3 and aPKC function directs cells towards the ICM in the preimplantation mouse embryo. J Cell Sci. 2005;118:505–15.PubMedCrossRefGoogle Scholar
  76. 76.
    Antczak M, Van Blerkom J. Oocyte influences on early development: the regulatory proteins leptin and STAT3 are polarized in mouse and human oocytes and differentially distributed within the cells of the preimplantation stage embryo. Mol Hum Reprod. 1997;3:1067–86.PubMedCrossRefGoogle Scholar
  77. 77.
    Antczak M, Van Blerkom J. Temporal and spatial aspects of fragmentation in early human embryos: possible effects on developmental competence and association with the differential elimination of regulatory proteins from polarized domains. Hum Reprod. 1999;14:429–47.PubMedCrossRefGoogle Scholar
  78. 78.
    Johnson MH, McConnell JM. Lineage allocation and cell polarity during mouse embryogenesis. Semin Cell Dev Biol. 2004;15:583–97.PubMedCrossRefGoogle Scholar
  79. 79.
    Schulz LC, Roberts RM. Dynamic changes in leptin distribution in the progression from ovum to blastocyst of the pre-implantation mouse embryo. Reproduction. 2011;141:767–77.PubMedCrossRefGoogle Scholar
  80. 80.
    Zernicka-Goetz M. The first cell-fate decisions in the mouse embryo: destiny is a matter of both chance and choice. Curr Opin Genet Dev. 2006;16:406–12.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Anna Ajduk
    • 1
    • 2
    Email author
  • Agnieszka Jedrusik
    • 2
  • Magdalena Zernicka-Goetz
    • 2
  1. 1.Department of Embryology, Faculty of BiologyUniversity of WarsawWarsawPoland
  2. 2.The Wellcome Trust/Cancer Research Gurdon InstituteUniversity of CambridgeCambridgeUK

Personalised recommendations