Cell and Tissue Research

, Volume 365, Issue 1, pp 197–208 | Cite as

Role of Notch signaling in granulosa cell proliferation and polyovular follicle induction during folliculogenesis in mouse ovary

  • Karin J. Terauchi
  • Yuri Shigeta
  • Taisen Iguchi
  • Tomomi SatoEmail author
Regular Article


In the fetal mouse ovary, oocytes are connected by an intercellular bridge and form germ cell cysts. Folliculogenesis begins after birth. To study the role of Notch signaling in folliculogenesis, double-immunohistochemical localization of laminin and Ki-67 was performed in mouse ovaries from embryonic day 17.5 (E17.5) to postnatal day 4 (P4). Most cysts and follicles contained Ki-67-negative cells; however, a few Ki-67-positive cells were present in cysts from E17.5 through P4, indicating that a small number of pre-granulosa cells continue to proliferate during folliculogenesis. To examine the effects of an inhibitor of Notch signaling (DAPT) and a synthetic estrogen (diethylstilbestrol [DES]) on folliculogenesis, an organ-culture system was established. The numbers of cysts, primordial follicles (PrFs) and primary follicles were unchanged by DES, whereas the total number of PrFs and of PrFs with Ki-67-negative cells was reduced by DAPT. In organ-cultured neonatal ovaries, only DAPT treatment increased degenerating cells defined as oocytes. On the contrary, the number of polyovular follicles (PFs) and the PF incidence were significantly increased in ovaries organ-cultured with DES at day 20 post-grafting. In organ-cultured fetal and neonatal ovaries, DAPT reduced Notch 3 and Hey2 mRNAs, whereas DES increased Hey2 mRNA. These results suggest that Notch signaling in fetal ovaries is involved with PrF assembly by the regulation of oocyte survival rather than by cell proliferation. In PF induction, as a result of the disruption of interactions between oocytes and pre-granulosa cells, DES and Notch signaling act independently.


Diethylstilbestrol Pre-granulosa cells Germ cell cysts Laminin Ki67 



We thank Dr. Raphael Guzman, Department of Molecular Cell Biology and Cancer Research Laboratory of University of California at Berkeley, for his critical reading of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors have nothing to disclose.

Supplementary material

441_2016_2371_MOESM1_ESM.docx (60 kb)
Table 1 (DOCX 59 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Karin J. Terauchi
    • 1
  • Yuri Shigeta
    • 2
  • Taisen Iguchi
    • 3
  • Tomomi Sato
    • 1
    • 2
    Email author
  1. 1.Graduate School of NanobioscienceYokohama City UniversityYokohamaJapan
  2. 2.International College of Arts and SciencesYokohama City UniversityYokohamaJapan
  3. 3.National Institute for Basic Biology, National Institutes of Natural SciencesThe Graduate University for Advanced Studies and Okazaki Institute for Integrative BioscienceOkazakiJapan

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