Journal of Assisted Reproduction and Genetics

, Volume 28, Issue 7, pp 583–589

Premature ovarian failure in nobox-deficient mice is caused by defects in somatic cell invasion and germ cell cyst breakdown

  • Agnieszka Lechowska
  • Szczepan Bilinski
  • Youngsok Choi
  • Yonghyun Shin
  • Malgorzata Kloc
  • Aleksandar Rajkovic
Gonadal Physiology and Disease

Abstract

Purpose

To understand the mechanism of premature ovarian failure (POF).

Methods

The ultrastructural (electron microscopy) analysis of primordial ovarian follicles in Nobox deficient mice.

Results

We studied, for the first time, the fate of oogonia in embryonic (prenatal) mouse ovaries and showed that the abolishment of the transition from germ cell cysts to primordial follicles in the ovaries of Nobox deficient mice is caused by defects in germ cell cyst breakdown, leading to the formation of syncytial follicles instead of primordial follicles.

Conclusions

These results indicate that POF syndrome in Nobox deficient mice results from the faulty signaling between somatic and germ line components during embryonic development. In addition, the extremely unusual and abnormal presence of adherens junctions between unseparated oocytes within syncytial follicles indicates that faulty communication between somatic and germ cells is involved in, or leads to, abnormalities in the cell adhesion program.

Keywords

Premature ovarian failure Nobox Homeobox Ovary Germ cells 

References

  1. 1.
    Choi Y, Rajkovic A. Genetics of early mammalian folliculogenesis. Cell Mol Life Sci. 2006a;63:579–90.PubMedCrossRefGoogle Scholar
  2. 2.
    Choi Y, Rajkovic A. Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters. J Biol Chem. 2006b;281:35747–56.PubMedCrossRefGoogle Scholar
  3. 3.
    Choi Y, Qin Y, Berger MF, Ballow DJ, Bulyk ML, Rajkovic A. A Microarray analyses of newborn mouse ovaries lacking Nobox. Biol Reprod. 2007;77:312–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Huntriss J, Hinkins M, Picton HM. cDNA cloning and expression of the human NOBOX gene in oocytes and ovarian follicles. Mol Hum Reprod. 2006;12:283–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet. 2007;81:576–81.PubMedCrossRefGoogle Scholar
  6. 6.
    Qin Y, Shi Y, Zhao Y, Carson SA, Simpson JL, Chen ZJ. Mutation analysis of NOBOX homeodomain in Chinese women with premature ovarian failure. Fertil Steril. 2009;91:1507–9.PubMedCrossRefGoogle Scholar
  7. 7.
    Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science. 2004;305:1157–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Simpson JL. Genetic and phenotypic heterogeneity in ovarian failure: overview of selected candidate genes. Ann NY Acad Sci. 2008;1135:146–54.PubMedCrossRefGoogle Scholar
  9. 9.
    Suzumori N, Yan C, Matzuk MM, Rajkovic A. Nobox is a homeobox-encoding gene preferentially expressed in primordial and growing oocytes. Mech Dev. 2002;111:137–41.PubMedCrossRefGoogle Scholar
  10. 10.
    Suzumori N, Pangas SA, Rajkovic A. Candidate genes for premature ovarian failure. Curr Med Chem. 2007;14:353–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Kloc M, Bilinski S, Dougherty MT, Brey EM, Etkin LD. Formation, architecture and polarity of female germline cyst in Xenopus. Dev Biol. 2004;266:43–61.PubMedCrossRefGoogle Scholar
  12. 12.
    Kloc M, Jaglarz M, Dougherty M, Stewart MD, Nel-Themaat L, Bilinski S. Mouse early oocytes are transiently polar: three-dimensional and ultrastructural analysis. Exp Cell Res. 2008;314:3245–54.PubMedCrossRefGoogle Scholar
  13. 13.
    Pepling ME, Spradling AC. Female mouse germ cells form synchronously dividing cysts. Development. 1998;125:3323–8.PubMedGoogle Scholar
  14. 14.
    Bilinski SM, Jaglarz MK, Dougherty MT, Kloc M. Electron microscopy, immunostaining, cytoskeleton visualization, in situ hybridization, and three-dimensional reconstruction of Xenopus oocytes. Methods. 2010;51:11–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Choi Y, Yuan D, Rajkovic A. Germ cell-specific transcriptional regulator Sohlh2 is essential for early mouse folliculogenesis and oocyte-specific gene expression. Biol Reprod. 2008;79:1176–82.PubMedCrossRefGoogle Scholar
  16. 16.
    Greenbaum MP, Yan W, Wu M-H, Lin Y-N, Agno JE, Sharma M, et al. TEX14 is essential for intercellular bridges and fertility in male mice. PNAS. 2006;103:4982–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Bogard N, Lan L, Xu J, Cohen RS. Rab11 maintains connections between germline stem cells and niche cells in the Drosophila ovary. Development. 2007;134:3413–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Cerda J, Reidenbach S, Pratzel S, Franke WW. Cadherin-catenin complexes during zebrafish oogenesis: heterotypic junctions between oocytes and follicle cells. Biol Reprod. 1999;61:692–704.PubMedCrossRefGoogle Scholar
  19. 19.
    Hierholzer A, Kempler R. Beta-catenin-mediated signaling and cell adhesion in postgastrulation mouse embryos. Dev Dyn. 2010;239:191–9.PubMedGoogle Scholar
  20. 20.
    Duta S, Pepling ME (2009) A drop in maternal estradiol levels correlates with cyst breakdown and may affect meiotic cell cycle progression. Biol Rep. 81, abstract 479.Google Scholar
  21. 21.
    Chen Y, Jefferson WN, Newbold RR, Padilla-Banks E, Pepling ME. Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology. 2007;148:3580–90.PubMedCrossRefGoogle Scholar
  22. 22.
    Monti M, Redi C. Oogenesis specific genes (Nobox, Oct4, Bmp15, Gdf9, Oogenesin1 and Oogenesin2) are differentially expressed during natural and gonadotropin-induced mouse follicular development. Mol Reprod Dev. 2009;76:994–1003.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Agnieszka Lechowska
    • 1
  • Szczepan Bilinski
    • 1
  • Youngsok Choi
    • 2
  • Yonghyun Shin
    • 3
  • Malgorzata Kloc
    • 4
  • Aleksandar Rajkovic
    • 3
  1. 1.Institute of ZoologyJagiellonian UniversityKrakowPoland
  2. 2.Department of Biomedical SciencesCHA UniversitySeoulThe Republic of Korea
  3. 3.Magee Women’s Research Institute, Department of Obstetrics and Gynecology and Reproductive SciencesUniversity of PittsburghPittsburghUSA
  4. 4.Department of SurgeryThe Methodist Hospital and The Methodist Hospital Research InstituteHoustonUSA

Personalised recommendations