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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

Abstract

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.

Keywords

Diethylstilbestrol Pre-granulosa cells Germ cell cysts Laminin Ki67 

Notes

Acknowledgments

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)

References

  1. Aharoni D, Meiri I, Atzmon R, Vlodavsky I, Amsterdam A (1997) Differential effect of components of the extracellular matrix on differentiation and apoptosis. Curr Biol 7:43–51CrossRefPubMedGoogle Scholar
  2. Aumailley M, Bruckner-Tuderman L, Carter WG, Deutzmann R, Edgar D, Ekblom P, Engel J, Engvall E, Hohenester E, Jones JC, Kleinman HK, Marinkovich MP, Martin GR, Mayer U, Meneguzzi G, Miner JH, Miyazaki K, Patarroyo M, Paulsson M, Quaranta V, Sanes JR, Sasaki T, Sekiguchi K, Sorokin LM, Talts JF, Tryggvason K, Uitto J, Virtanen I, Mark K, Wewer UM, Yamada Y, Yurchenco PD (2005) A simplified laminin nomenclature. Matrix Biol 24:326–332CrossRefPubMedGoogle Scholar
  3. Berkholtz CB, Lai BE, Woodruff TK, Shea LD (2006) Distribution of extracellular matrix proteins type I collagen, type IV collagen, fibronectin, and laminin in mouse folliculogenesis. Histochem Cell Biol 126:583–592CrossRefPubMedPubMedCentralGoogle Scholar
  4. Chen CL, Fu XF, Wang LQ, Wang JJ, Ma HG, Cheng SF, Hou ZM, Ma JM, Quan GB, Shen W, Li L (2014)Primordial follicle assembly was regulated by Notch signaling pathway in the mice.Mol Biol Rep 41:1891-1899CrossRefPubMedGoogle Scholar
  5. Chen Y, Jefferson WN, Newbold RR, Padilla-Banks E, Pepling ME (2007) Estradiol, progesterone, and genistein inhibit oocyte nest breakdown and primordial follicle assembly in the neonatal mouse ovary in vitro and in vivo. Endocrinology 148:3580–3590CrossRefPubMedGoogle Scholar
  6. Dovey HF, John V, Anderson JP, Chen LZ, Saint AP de, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ, Hu KL, Johnson-Wood KL, Kennedy SL, Kholodenko D, Knops JE, Latimer LH, Lee M, Liao Z, Lieberburg IM, Motter RN, Mutter LC, Nietz J, Quinn KP, Sacchi KL, Seubert PA, Shopp GM, Thorsett ED, Tung JS, Wu J, Yang S, Yin CT, Schenk DB, May PC, Altstiel LD, Bender MH, Boggs LN, Britton TC, Clemens JC, Czilli DL, Dieckman-McGinty DK, Droste JJ, Fuson KS, Gitter BD, Hyslop PA, Johnstone EM, Li WY, Little SP, Mabry TE, Miller FD, Audia JE (2001) Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. J Neurochem 76:173–181Google Scholar
  7. Hori K, Sen A, Artavanis-Tsakonas S (2013) Notch signaling at a glance. J Cell Sci 126:2135–2140CrossRefPubMedPubMedCentralGoogle Scholar
  8. Iguchi T, Takasugi N (1986) Polyovular follicles in the ovary of immature mice exposed prenatally to diethylstilbestrol. Anat Embryol 175:53–55CrossRefPubMedGoogle Scholar
  9. Iguchi T, Fukazawa Y, Uesugi Y, Takasugi N (1990) Polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol in vivo and in vitro. Biol Reprod 43:478–484CrossRefPubMedGoogle Scholar
  10. Irving-Rodgers HF, Hummitzsch K, Murdiyarso LS, Bonner WM, Sado NY, Couchman JR, Sorokin LM, Rodgers RJ (2010) Dynamics of extracellular matrix in ovarian follicles and corpora lutea of mice. Cell Tissue Res 339:613–624CrossRefPubMedGoogle Scholar
  11. Kim H, Nakajima T, Hayashi S, Chambon P, Watanabe H, Iguchi T, Sato T (2009) Effects of diethylstilbestrol on programmed oocyte death and induction of polyovular follicles in neonatal mouse ovaries. Biol Reprod 81:1002–1009CrossRefPubMedGoogle Scholar
  12. Kirigaya A, Kim H, Hayashi S, Chambon P, Watanabe H, Iguchi T, Sato T (2009) Involvement of estrogen receptor β in the induction of polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol. Zool Sci 26:704–712CrossRefPubMedGoogle Scholar
  13. Knight PG, Satchell L, Glister C (2012) Intra-ovarian roles of activins and inhibins. Mol Cell Endocrinol 359:53–65CrossRefPubMedGoogle Scholar
  14. Lechowska A, Bilinski S, Choi Y, Shin Y, Kloc M, Rajkovic A (2011) Premature ovarian failure in nobox-deficient mice is caused by defects in somatc cell invasion and germ cell cyst breakdown. J Assist Reprod Genet 28:583–589CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mazaud S, Guyot R, Guigon CJ, Coudouel N, Magueresse-Battistomi BL, Magre S (2005) Basal membrane remodeling during follicle histogenesis in the rat ovary: contribution of proteinases of the MMP and PA families. Dev Biol 277:403–416CrossRefPubMedGoogle Scholar
  16. Mork L, Maatouk DM, McMahon JA, Guo JJ, Zhang P, McMahon AP, Capel B (2012) Temporal differences in granulosa cell specification in the ovary reflect distinct follicle fates in mice. Biol Reprod 86:37CrossRefPubMedGoogle Scholar
  17. Oktay K, Karlikaya G, Akman O, Ojakian GK, Oktay M (2000) Interaction of extracellular matrix and activin-a in the initiation of follicle growth in the mouse ovary. Biol Reprod 63:457–461CrossRefPubMedGoogle Scholar
  18. Pepling ME, Spradling AC (1998) Female mouse germ cells form synchronously dividing cysts. Development 125:3323–3328PubMedGoogle Scholar
  19. Pepling ME, Spradling AC (2001) Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol 234:339–351CrossRefPubMedGoogle Scholar
  20. Peters H (1969) The development of mice ovary from birth to maturity. Acta Endocrinol 62:98–116PubMedGoogle Scholar
  21. Suzuki A, Sugihara A, Uchida K, Sato T, Ohta Y, Katsu Y, Watanabe H, Iguchi T (2002) Developmental effects of perinatal exposure to bisphenol-A and diethylstilbestrol on reproductive organs in female mice. Reprod Toxicol 16:107–116CrossRefPubMedGoogle Scholar
  22. Trombly DJ, Woodruff TK, Mayo KE (2009) Suppression of notch signaling in the neonatal mouse ovary decreases primordial follicle formation. Endocrinology 150:1014–1024CrossRefPubMedGoogle Scholar
  23. Vanorny DA, Prasasya RD, Chalpe AJ, Kilen SM, Mayo KE (2014) Notch signaling regulates ovarian follicle formation and coordinates follicular growth. Mol Endocrinol 28:499–511CrossRefPubMedPubMedCentralGoogle Scholar
  24. Xu J, Gridley T (2013) Notch2 is required in somatic cells for breakdown of ovarian germ-cell nests and formation of primordial follicles. BMC Biol 11:13–26CrossRefPubMedPubMedCentralGoogle Scholar
  25. Zhang CP, Yang J-L, Zhang J, Li L, Huang L, Ji S-Y, Hu Z-Y, Gao F, Liu Y-X (2011) Notch signaling is involved in ovarian follicle development by regulating granulosa cell proliferation. Endocrinology 152:2437–2447CrossRefPubMedGoogle Scholar

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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