Cell and Tissue Research

, Volume 375, Issue 3, pp 743–754 | Cite as

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

  • Fumiya Ojima
  • Yuka Saito
  • Yukiko Tsuchiya
  • Maho Ogoshi
  • Hiroshi Fukamachi
  • Kenichi Inagaki
  • Fumio Otsuka
  • Sakae Takeuchi
  • Sumio TakahashiEmail author
Regular Article


We previously demonstrated that female Runx3 knockout (Runx3−/−) mice were anovulatory and their uteri were atrophic and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examine the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3−/− mouse ovaries, the numbers of primary and antral follicles were lower than those in wild-type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba and Inhbb) was also decreased in ovaries from the Runx3−/− mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3−/− mice than those in wt mice. Follicle-stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3−/− granulosa cells in culture but the mRNA level in Runx3−/− granulosa cells was lower than that in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and luteinizing hormone (LH) β subunit mRNA levels were decreased in Runx3−/− mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells.


Ovary Follicle Estrogen Mouse Runx3 



This study was supported in part by the Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science to S.T. (No. 26440167).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Fumiya Ojima
    • 1
    • 2
  • Yuka Saito
    • 2
  • Yukiko Tsuchiya
    • 2
  • Maho Ogoshi
    • 2
  • Hiroshi Fukamachi
    • 3
  • Kenichi Inagaki
    • 4
  • Fumio Otsuka
    • 4
  • Sakae Takeuchi
    • 2
  • Sumio Takahashi
    • 2
    Email author
  1. 1.Department of Natural Sciences and BiologyKawasaki Medical SchoolOkayamaJapan
  2. 2.Department of Biology, The Graduate School of Natural Science and TechnologyOkayama UniversityTsushimaJapan
  3. 3.The Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityTokyoJapan
  4. 4.The Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayama UniversityOkayamaJapan

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