Oogenesis pp 129-139 | Cite as

Regulation of Oogenesis by Oocyte-Specific Gene Networks

  • Swamy K. Tripurani
  • Stephanie A. PangasEmail author


Although, development of traditional and conditional transgenic knockout mice models has been critical in revealing how oocyte-expressed transcripts regulate oocyte growth and embryo development, many aspects concerning reproduction remain to be determined. Recent studies have demonstrated that oocyte-specific transcriptional regulators play essential roles in regulating various stages of oogenesis, folliculogenesis and early embryonic development. In this book chapter, we categorized and reviewed transcriptional regulators based upon their known function in germ cells: (1) those that are specifically expressed in the female germline and appear to function only in oocytes (Figla and Nobox); (2) those that are expressed in both male and female germline and affect both male and female fertility (Sohlh1 and Sohlh2); and (3) those that are highly expressed in germ cells, but show additional expression in other somatic tissues (Lhx8, Pou5f1 and Yy1). These investigations will provide insight into the regulation of mammalian fertility.


Transcription factor Germ cell Reproduction Fertility 


  1. 1.
    Eppig J. Oocyte control of ovarian follicular development and function in mammals. Reproduction. 2001;122(6):829–38.PubMedCrossRefGoogle Scholar
  2. 2.
    Eppig JJ, Wigglesworth K, Pendola FL. The mammalian oocyte orchestrates the rate of ovarian follicular development. Proc Natl Acad Sci USA. 2002;99(5):2890–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Edson MA, Nagaraja AK, Matzuk MM. The mammalian ovary from genesis to revelation. Endocr Rev. 2009;30(6):624–712.PubMedCrossRefGoogle Scholar
  4. 4.
    Gosden RG. Oogenesis as a foundation for embryogenesis. Mol Cell Endocrinol. 2002;186(2):149–53.PubMedCrossRefGoogle Scholar
  5. 5.
    Cui X-S, Li X-Y, Yin X-J, Kong IK, Kang J-J, Kim N-H. Maternal gene transcription in mouse oocytes: genes implicated in oocyte maturation and fertilization. J Reprod Dev. 2007;53(2):405–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Li L, Zheng P, Dean J. Maternal control of early mouse development. Development. 2010;137(6):859–70.PubMedCrossRefGoogle Scholar
  7. 7.
    Rajkovic A, Matzuk M. Functional analysis of oocyte-expressed genes using transgenic models. Mol Cell Endocrinol. 2002;187(1–2):5–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Jorgez CJ, Lin Y-N, Matzuk MM. Genetic manipulations to study reproduction. Mol Cell Endocrinol. 2005;234(1–2):127–35.PubMedCrossRefGoogle Scholar
  9. 9.
    Andreu-Vieyra C, Lin Y-N, Matzuk MM. Mining the oocyte transcriptome. Trends Endocrinol Metab. 2006;17(4):136–43.PubMedCrossRefGoogle Scholar
  10. 10.
    Aiba K, Carter MG, Matoba R, Ko MSH. Genomic approaches to early embryogenesis and stem cell biology. Semin Reprod Med. 2006;24(5):330–9.PubMedCrossRefGoogle Scholar
  11. 11.
    Sun Q-Y, Liu K, Kikuchi K. Oocyte-specific knockout: a novel in vivo approach for studying gene functions during folliculogenesis, oocyte maturation, fertilization, and embryogenesis. Biol Reprod. 2008;79(6):1014–20.PubMedCrossRefGoogle Scholar
  12. 12.
    Epifano O, Dean J. Genetic control of early folliculogenesis in mice. Trends Endocrinol Metab. 2002;13(4):169–73.PubMedCrossRefGoogle Scholar
  13. 13.
    Acevedo N, Smith GD. Oocyte-specific gene signaling and its regulation of mammalian reproductive potential. Front Biosci. 2005;10:2335–45.PubMedCrossRefGoogle Scholar
  14. 14.
    Pangas SA, Rajkovic A. Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update. 2006;12(1):65–76.PubMedCrossRefGoogle Scholar
  15. 15.
    Zheng P, Dean J. Oocyte-specific genes affect folliculogenesis, fertilization, and early development. Semin Reprod Med. 2007;25(4):243–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Jagarlamudi K, Rajkovic A. Oogenesis: transcriptional regulators and mouse models. Mol Cell Endocrinol. 2012;356(1–2):31–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Soyal SM, Amleh A, Dean J. FIGalpha, a germ cell-specific transcription factor required for ovarian follicle formation. Development. 2000;127(21):4645–54.PubMedGoogle Scholar
  18. 18.
    Rajkovic A, Pangas SA, Ballow D, Suzumori N, Matzuk MM. NOBOX deficiency disrupts early folliculogenesis and oocyte-specific gene expression. Science. 2004;305(5687):1157–9.PubMedCrossRefGoogle Scholar
  19. 19.
    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(6):1176–82.PubMedCrossRefGoogle Scholar
  20. 20.
    Choi Y, Ballow DJ, Xin Y, Rajkovic A. Lim homeobox gene, lhx8, is essential for mouse oocyte differentiation and survival. Biol Reprod. 2008;79(3):442–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Kehler J, Tolkunova E, Koschorz B, Pesce M, Gentile L, Boiani M, et al. Oct4 is required for primordial germ cell survival. EMBO Rep. 2004;5(11):1078–83.PubMedCrossRefGoogle Scholar
  22. 22.
    Griffith GJ, Trask MC, Hiller J, Walentuk M, Pawlak JB, Tremblay KD, et al. Yin-yang1 is required in the mammalian oocyte for follicle expansion. Biol Reprod. 2011;84(4):654–63.PubMedCrossRefGoogle Scholar
  23. 23.
    Liang L, Soyal SM, Dean J. FIGalpha, a germ cell specific transcription factor involved in the coordinate expression of the zona pellucida genes. Development. 1997;124(24):4939–47.PubMedGoogle Scholar
  24. 24.
    Hu W, Gauthier L, Baibakov B, Jimenez-Movilla M, Dean J. FIGLA, a basic helix-loop-helix transcription factor, balances sexually dimorphic gene expression in postnatal oocytes. Mol Cell Biol. 2010;30(14):3661–71.PubMedCrossRefGoogle Scholar
  25. 25.
    Bayne R, da Silva S, Anderson R. Increased expression of the FIGLA transcription factor is associated with primordial follicle formation in the human fetal ovary. Mol Hum Reprod. 2004;10(6):373–81.PubMedCrossRefGoogle Scholar
  26. 26.
    Onichtchouk D, Aduroja K, Belting H-G, Gnügge L, Driever W. Transgene driving GFP expression from the promoter of the zona pellucida gene zpc is expressed in oocytes and provides an early marker for gonad differentiation in zebrafish. Dev Dyn. 2003;228(3):393–404.PubMedCrossRefGoogle Scholar
  27. 27.
    Kanamori A. Systematic identification of genes expressed during early oogenesis in medaka. Mol Reprod Dev. 2000;55(1):31–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Tripurani KS, Lee BK, Smith WG, et al. Cloning and expression of bovine factor in the germline alpha (FIGLA) in oocytes and early embryos: a potential target of microrna-212. Reprod Fertil Dev. 2010;23(1):109–9.CrossRefGoogle Scholar
  29. 29.
    Joshi S, Davies H, Sims LP, Levy SE, Dean J. Ovarian gene expression in the absence of FIGLA, an oocyte-specific transcription factor. BMC Dev Biol. 2007;7:67.PubMedCrossRefGoogle Scholar
  30. 30.
    Zhao H, Chen Z-J, Qin Y, Shi Y, Wang S, Choi Y, et al. Transcription factor FIGLA is mutated in patients with premature ovarian failure. Am J Hum Genet. 2008;82(6):1342–8.PubMedCrossRefGoogle Scholar
  31. 31.
    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(1–2):137–41.PubMedCrossRefGoogle Scholar
  32. 32.
    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(5):283–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Li G, Li M, Fang W, Wang W, He Y, Song X, et al. Cloning and characterization of porcine NOBOX gene. Sheng Wu Gong Cheng Xue Bao. 2009;25(8):1130–7.PubMedGoogle Scholar
  34. 34.
    Tripurani SK, Lee K-B, Wang L, Wee G, Smith GW, Lee YS, et al. A novel functional role for the oocyte-specific transcription factor newborn ovary homeobox (NOBOX) during early embryonic development in cattle. Endocrinology. 2011;152(3):1013–23.PubMedCrossRefGoogle Scholar
  35. 35.
    Lechowska A, Bilinski S, Choi Y, Shin Y, Kloc M, Rajkovic A. Premature ovarian failure in nobox-deficient mice is caused by defects in somatic cell invasion and germ cell cyst breakdown. J Assist Reprod Genet. 2011;28(7):583–9.PubMedCrossRefGoogle Scholar
  36. 36.
    Choi Y, Qin Y, Berger MF, Ballow DJ, Bulyk ML, Rajkovic A. Microarray analyses of newborn mouse ovaries lacking Nobox. Biol Reprod. 2007;77(2):312–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Choi Y, Rajkovic A. Characterization of NOBOX DNA binding specificity and its regulation of Gdf9 and Pou5f1 promoters. J Biol Chem. 2006;281(47):35747–56.PubMedCrossRefGoogle Scholar
  38. 38.
    Dong J, Albertini DF, Nishimori K, Kumar TR, Lu N, Matzuk MM. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature. 1996;383(6600):531–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Carabatsos M, Elvin J, Matzuk M, Albertini D. Characterization of oocyte and follicle development in growth differentiation factor-9-deficient mice. Dev Biol. 1998;204(2):373–84.PubMedCrossRefGoogle Scholar
  40. 40.
    Richards JS, Pangas SA. New insights into ovarian function. Handb Exp Pharmacol. 2010;1(198):3–27.CrossRefGoogle Scholar
  41. 41.
    Bouilly J, Bachelot A, Broutin I, Touraine P, Binart N. Novel NOBOX loss-of-function mutations account for 6.2 % of cases in a large primary ovarian insufficiency cohort. Hum Mutat. 2011;32(10):1108–13.PubMedCrossRefGoogle Scholar
  42. 42.
    Qin Y, Choi Y, Zhao H, Simpson JL, Chen Z-J, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet. 2007;81(3):576–81.PubMedCrossRefGoogle Scholar
  43. 43.
    Zhao X, Suzumori N, Yamaguchi M, Suzumori K. Mutational analysis of the homeobox region of the human NOBOX gene in Japanese women who exhibit premature ovarian failure. Fertil Steril. 2005;83(6):1843–4.PubMedCrossRefGoogle Scholar
  44. 44.
    Rossi E, Verri AP, Patricelli MG, Destefani V, Ricca I, Vetro A, et al. A 12 Mb deletion at 7q33-q35 associated with autism spectrum disorders and primary amenorrhea. Eur J Med Genet. 2008;51(6):631–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Qin Y, Shi Y, Zhao Y, Carson SA, Simpson JL, Chen Z-J. Mutation analysis of NOBOX homeodomain in Chinese women with premature ovarian failure. Fertil Steril. 2009;91(4 Suppl):1507–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Ballow DJ, Xin Y, Choi Y, Pangas SA, Rajkovic A. Sohlh2 is a germ cell-specific bHLH transcription factor. Gene Expr Patterns. 2006;6(8):1014–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Pangas SA, Choi Y, Ballow DJ, Zhao Y, Westphal H, Matzuk MM, et al. Oogenesis requires germ cell-specific transcriptional regulators Sohlh1 and Lhx8. Proc Natl Acad Sci USA. 2006;103(21):8090–5.PubMedCrossRefGoogle Scholar
  48. 48.
    Choi Y, Jeon S, Choi M, M-h L, Park M, Lee DR, et al. Mutations in SOHLH1 gene associate with nonobstructive azoospermia. Hum Mutat. 2010;31(7):788–93.PubMedCrossRefGoogle Scholar
  49. 49.
    Lan Z-J, Xu X, Cooney AJ. Differential oocyte-specific expression of Cre recombinase activity in GDF-9-iCre, Zp3cre, and Msx2Cre transgenic mice. Biol Reprod. 2004;71(5):1469–74.PubMedCrossRefGoogle Scholar
  50. 50.
    Banerjee-Basu S, Baxevanis AD. Molecular evolution of the homeodomain family of transcription factors. Nucleic Acids Res. 2001;29(15):3258–69.PubMedCrossRefGoogle Scholar
  51. 51.
    Srivastava M, Larroux C, Lu DR, Mohanty K, Chapman J, Degnan BM, et al. Early evolution of the LIM homeobox gene family. BMC Biol. 2010;8:4.PubMedCrossRefGoogle Scholar
  52. 52.
    Hobert O, Westphal H. Functions of LIM-homeobox genes. Trends Genet. 2000;16(2):75–83.PubMedCrossRefGoogle Scholar
  53. 53.
    Zhao Y, Guo YJ, Tomac AC, Taylor NR, Grinberg A, Lee EJ, et al. Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene lhx8. Proc Natl Acad Sci USA. 1999;96(26):15002–6.PubMedCrossRefGoogle Scholar
  54. 54.
    Zhao Y, Marín O, Hermesz E, Powell A, Flames N, Palkovits M, et al. The LIM-homeobox gene Lhx8 is required for the development of many cholinergic neurons in the mouse forebrain. Proc Natl Acad Sci USA. 2003;100(15):9005–10.PubMedCrossRefGoogle Scholar
  55. 55.
    Schöler HR. Octamania: the POU factors in murine development. Trends Genet. 1991;7(10):323–9.PubMedCrossRefGoogle Scholar
  56. 56.
    Pan GJ, Chang ZY, Schöler HR, Pei D. Stem cell pluripotency and transcription factor Oct4. Cell Res. 2002;12(5–6):321–9.PubMedCrossRefGoogle Scholar
  57. 57.
    Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, et al. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell. 1998;95(3):379–91.PubMedCrossRefGoogle Scholar
  58. 58.
    Velkey JM, O’Shea KS. Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells. Genesis. 2003;37(1):18–24.PubMedCrossRefGoogle Scholar
  59. 59.
    Niwa H, Miyazaki J, Smith AG. Quantitative expression of Oct-3/4 defines differentiation, dedifferentiation or self-renewal of ES cells. Nat Genet. 2000;24(4):372–6.PubMedCrossRefGoogle Scholar
  60. 60.
    Gidekel S, Pizov G, Bergman Y, Pikarsky E. Oct-3/4 is a dose-dependent oncogenic fate determinant. Cancer Cell. 2003;4(5):361–70.PubMedCrossRefGoogle Scholar
  61. 61.
    Pesce M, Wang X, Wolgemuth DJ, Schöler H. Differential expression of the Oct-4 transcription factor during mouse germ cell differentiation. Mech Dev. 1998;71(1–2):89–98.PubMedCrossRefGoogle Scholar
  62. 62.
    Seto E, Shi Y, Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991;354(6350):241–5.PubMedCrossRefGoogle Scholar
  63. 63.
    Ye J, Cippitelli M, Dorman L, Ortaldo JR, Young HA. The nuclear factor YY1 suppresses the human gamma interferon promoter through two mechanisms: inhibition of AP1 binding and activation of a silencer element. Mol Cell Biol. 1996;16(9):4744–53.PubMedGoogle Scholar
  64. 64.
    Galvin KM, Shi Y. Multiple mechanisms of transcriptional repression by YY1. Mol Cell Biol. 1997;17(7):3723–32.PubMedGoogle Scholar
  65. 65.
    Shi Y, Lee JS, Galvin KM. Everything you have ever wanted to know about Yin Yang 1. Biochim Biophys Acta. 1997;1332(2):F49–66.PubMedGoogle Scholar
  66. 66.
    Bushmeyer SM, Atchison ML. Identification of YY1 sequences necessary for association with the nuclear matrix and for transcriptional repression functions. J Cell Biochem. 1998;68(4):484–99.PubMedCrossRefGoogle Scholar
  67. 67.
    Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y. Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol. 1999;19(10):7237–44.PubMedGoogle Scholar
  68. 68.
    Rezai-Zadeh N, Zhang X, Namour F, Fejer G, Wen Y-D, Yao Y-L, et al. Targeted recruitment of a histone H4-specific methyltransferase by the transcription factor YY1. Genes Dev. 2003;17(8):1019–29.PubMedCrossRefGoogle Scholar
  69. 69.
    Baumeister P, Luo S, Skarnes WC, Sui G, Seto E, Shi Y, et al. Endoplasmic reticulum stress induction of the Grp78/BiP promoter: activating mechanisms mediated by YY1 and its interactive chromatin modifiers. Mol Cell Biol. 2005;25(11):4529–40.PubMedCrossRefGoogle Scholar
  70. 70.
    Satijn DP, Hamer KM, den Blaauwen J, Otte AP. The polycomb group protein EED interacts with YY1, and both proteins induce neural tissue in xenopus embryos. Mol Cell Biol. 2001;21(4):1360–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Kurisaki K, Kurisaki A, Valcourt U, Terentiev AA, Pardali K, Ten Dijke P, et al. Nuclear factor YY1 inhibits transforming growth factor beta- and bone morphogenetic protein-induced cell differentiation. Mol Cell Biol. 2003;23(13):4494–510.PubMedCrossRefGoogle Scholar
  72. 72.
    Elvin JA, Matzuk MM. Mouse models of ovarian failure. Rev Reprod. 1998;3(3):183–95.PubMedCrossRefGoogle Scholar
  73. 73.
    Suzumori N, Pangas SA, Rajkovic A. Candidate genes for premature ovarian failure. Curr Med Chem. 2007;14:1–6.CrossRefGoogle Scholar
  74. 74.
    Jagarlamudi K, Reddy P, Adhikari D, Liu K. Genetically modified mouse models for premature ovarian failure (POF). Mol Cell Endocrinol. 2010;315(1–2):1–10.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  1. 1.Department of Pathology and ImmunologyBaylor College of MedicineHoustonUSA
  2. 2.Department of Molecular and Cellular Biology, Department of Pathology and ImmunologyBaylor College of MedicineHoustonUSA

Personalised recommendations