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Expression of CCM2 and CCM3 during mouse gonadogenesis

  • Reproductive Physiology and Disease
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Abstract

Purpose

Three cerebral cavernous malformation (CCM) proteins, CCM1, CCM2, and CCM3, regulate cell-cell adhesion, cell shape and polarity, and most likely cell adhesion to extracellular matrix. Recently, CCM2 and CCM3 are known to be expressed in control and varicocele-induced rat testes, but little is known about these proteins during gonadogenesis. This led us to study the CCM proteins during the mouse gonadogenesis.

Methods

Neonatal (PND 0), postnatal, and adult mice testes and ovaries were obtained from mice. CCM2 and CCM3 expression were analyzed during mouse testicular and ovarian development by immunohistochemistry and quantitative real-time PCR.

Results

The results showed that in both sexes, Ccm2 and Ccm3 mRNA and protein were first detectable after gonadogenesis when the gonads were well differentiated and remained present until the adult stage. In the testis, CCM2 and CCM3 expression were restricted to the nuclei of Sertoli cells, suggesting a conserved role in testicular differentiation. In the ovary, the CCM2 and CCM3 proteins were localized in the cytoplasm of oocytes, suggesting an unexpected role during oogenesis. Quantitative real-time PCR (qRT-PCR) results showed that expression of Ccm2 and Ccm3 genes could play a role in the regulation of mouse gonadogenesis translational activation upon testicular and ovarian development.

Conclusions

The localization of CCM2 and CCM3 proteins show their different functions for CCM2 and CCM3 which may have important roles in testicular and ovarian differentiation. In conclusion, CCM2 and CCM3 may be involved in establishing the differential expression pattern in developing mouse testis and ovary.

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References

  1. Lonnie D. R. ER. Histological and histopathological evaluation of the testis: Cache River Pr; 1 edition 1990.

  2. Morrish BC, Sinclair AH. Vertebrate sex determination: many means to an end. Reproduction. 2002;124:447–57.

    Article  CAS  PubMed  Google Scholar 

  3. Koopman P, Munsterberg A, Capel B, Vivian N, Lovell-Badge R. Expression of a candidate sex-determining gene during mouse testis differentiation. Nature. 1990;348:450–2.

    Article  CAS  PubMed  Google Scholar 

  4. Wilhelm D, Koopman P. The makings of maleness: towards an integrated view of male sexual development. Nat Rev Genet. 2006;7:620–31.

    Article  CAS  PubMed  Google Scholar 

  5. Itman C, Miyamoto Y, Young J, Jans DA, Loveland KL. Nucleocytoplasmic transport as a driver of mammalian gametogenesis. Semin Cell Dev Biol. 2009;20:607–19.

    Article  CAS  PubMed  Google Scholar 

  6. Bendel-Stenzel M, Anderson R, Heasman J, Wylie C. The origin and migration of primordial germ cells in the mouse. Semin Cell Dev Biol. 1998;9:393–400.

    Article  CAS  PubMed  Google Scholar 

  7. Western PS, Miles DC, van den Bergen JA, Burton M, Sinclair AH. Dynamic regulation of mitotic arrest in fetal male germ cells. Stem Cells. 2008;26:339–47.

    Article  CAS  PubMed  Google Scholar 

  8. de Rooij DG, Russell LD. All you wanted to know about spermatogonia but were afraid to ask. J Androl. 2000;21:776–98.

    PubMed  Google Scholar 

  9. Nagano R, Tabata S, Nakanishi Y, Ohsako S, Kurohmaru M, Hayashi Y. Reproliferation and relocation of mouse male germ cells (gonocytes) during prespermatogenesis. Anat Rec. 2000;258:210–20.

    Article  CAS  PubMed  Google Scholar 

  10. Pepling ME, Spradling AC. Mouse ovarian germ cell cysts undergo programmed breakdown to form primordial follicles. Dev Biol. 2001;234:339–51.

    Article  CAS  PubMed  Google Scholar 

  11. McGee EA, Hsueh AJ. Initial and cyclic recruitment of ovarian follicles. Endocr Rev. 2000;21:200–14.

    CAS  PubMed  Google Scholar 

  12. Vanderhyden B. Molecular basis of ovarian development and function. Front Biosci. 2002;7:d2006–22.

    Article  CAS  PubMed  Google Scholar 

  13. Albertini DF. Regulation of meiotic maturation in the mammalian oocyte: interplay between exogenous cues and the microtubule cytoskeleton. Bioessays. 1992;14:97–103.

    Article  CAS  PubMed  Google Scholar 

  14. Buccione R, Schroeder AC, Eppig JJ. Interactions between somatic cells and germ cells throughout mammalian oogenesis. Biol Reprod. 1990;43:543–7.

    Article  CAS  PubMed  Google Scholar 

  15. Ben-Or S. Morphological and functional development of the ovary of the mouse. I. Morphology and histochemistry of the developing ovary in normal conditions and after FSH treatment. J Embryol Exp Morphol. 1963;11:1–11.

    CAS  PubMed  Google Scholar 

  16. Bachvarova R. Gene expression during oogenesis and oocyte development in mammals. Dev Biol (N Y 1985). 1985;1:453–524.

    CAS  Google Scholar 

  17. Cheng A, Le T, Palacios M, Bookbinder LH, Wassarman PM, Suzuki F, et al. Sperm-egg recognition in the mouse: characterization of sp56, a sperm protein having specific affinity for ZP3. J Cell Biol. 1994;125:867–78.

    Article  CAS  PubMed  Google Scholar 

  18. Knobil E, Neill’s JD, et al. The physiology of reproduction. 2nd ed. New York: Raven; 1994. p. 79–122.

    Google Scholar 

  19. Matzuk MM, Burns KH, Viveiros MM, Eppig JJ. Intercellular communication in the mammalian ovary: oocytes carry the conversation. Science. 2002;296:2178–80.

    Article  CAS  PubMed  Google Scholar 

  20. Riant F, Bergametti F, Ayrignac X, Boulday G, Tournier-Lasserve E. Recent insights into cerebral cavernous malformations: the molecular genetics of CCM. FEBS J. 2010;277:1070–5.

    Article  CAS  PubMed  Google Scholar 

  21. Nussbaum ES. Vascular malformations of the brain. Minn Med. 2013;96:40–3.

    PubMed  Google Scholar 

  22. Richardson BT, Dibble CF, Borikova AL, Johnson GL. Cerebral cavernous malformation is a vascular disease associated with activated RhoA signaling. Biol Chem. 2013;394:35–42.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Chan AC, Li DY, Berg MJ, Whitehead KJ. Recent insights into cerebral cavernous malformations: animal models of CCM and the human phenotype. FEBS J. 2010;277:1076–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Faurobert E, Albiges-Rizo C. Recent insights into cerebral cavernous malformations: a complex jigsaw puzzle under construction. FEBS J. 2010;277:1084–96.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Hilder TL, Malone MH, Bencharit S, Colicelli J, Haystead TA, Johnson GL, et al. Proteomic identification of the cerebral cavernous malformation signaling complex. J Proteome Res. 2007;6:4343–55.

    Article  CAS  PubMed  Google Scholar 

  26. Kleaveland B, Zheng X, Liu JJ, Blum Y, Tung JJ, Zou Z, et al. Regulation of cardiovascular development and integrity by the heart of glass-cerebral cavernous malformation protein pathway. Nat Med. 2009;15:169–76.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Whitehead KJ, Plummer NW, Adams JA, Marchuk DA, Li DY. Ccm1 is required for arterial morphogenesis: implications for the etiology of human cavernous malformations. Development. 2004;131:1437–48.

    Article  CAS  PubMed  Google Scholar 

  28. Whitehead KJ, Chan AC, Navankasattusas S, Koh W, London NR, Ling J, et al. The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med. 2009;15:177–84.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  29. Boulday G, Blecon A, Petit N, Chareyre F, Garcia LA, Niwa-Kawakita M, et al. Tissue-specific conditional CCM2 knockout mice establish the essential role of endothelial CCM2 in angiogenesis: implications for human cerebral cavernous malformations. Dis Model Mech. 2009;2:168–77.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Tanriover G, Sati L, Tekcan M, Demir N, Gunel M, Celik-Ozenci C. Presence of the brain proteins cerebral cavernous malformation-2 and cerebral cavernous malformation-3 in rat testes and their potential role in experimental varicocele. Fertil Steril. 2010;93:2716–22.

    Article  CAS  PubMed  Google Scholar 

  31. Rajah R, Glaser EM, Hirshfield AN. The changing architecture of the neonatal rat ovary during histogenesis. Dev Dyn. 1992;194:177–92.

    Article  CAS  PubMed  Google Scholar 

  32. Gougeon A. In: Filicori M, Flamigni C, editors. The ovary: regulation, dysfunction and treatment. Amsterdam: Elsevier Science B.V; 1996. p. 3–12.

    Google Scholar 

  33. Gougeon A, Busso D. Morphologic and functional determinants of primordial and primary follicles in the monkey ovary. Mol Cell Endocrinol. 2000;163:33–42.

    Article  CAS  PubMed  Google Scholar 

  34. Zawistowski JS, Stalheim L, Uhlik MT, Abell AN, Ancrile BB, Johnson GL, et al. CCM1 and CCM2 protein interactions in cell signaling: implications for cerebral cavernous malformations pathogenesis. Hum Mol Genet. 2005;14:2521–31.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang J, Rigamonti D, Dietz HC, Clatterbuck RE. Interaction between krit1 and malcavernin: implications for the pathogenesis of cerebral cavernous malformations. Neurosurgery. 2007;60:353–9.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Histology and Embryology, İstanbul Medipol University School of Medicine, İstanbul, Turkey

    Aylin Yaba

  2. Department of Histology and Embryology, Akdeniz University School of Medicine, 07070 Campus, Antalya, Turkey

    N. Ece Gungor Ordueri, Gamze Tanriover, Pinar Sahin, Necdet Demir & Ciler Celik-Ozenci

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  1. Aylin Yaba
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  2. N. Ece Gungor Ordueri
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  3. Gamze Tanriover
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  4. Pinar Sahin
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  5. Necdet Demir
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  6. Ciler Celik-Ozenci
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Correspondence to Ciler Celik-Ozenci.

Additional information

Capsule Expressions of CCM2 and CCM3 during mouse gonadal differentiation may be involved in establishing the regulation of gonad development.

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Yaba, A., Ordueri, N.E.G., Tanriover, G. et al. Expression of CCM2 and CCM3 during mouse gonadogenesis. J Assist Reprod Genet 32, 1497–1507 (2015). https://doi.org/10.1007/s10815-015-0559-2

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  • DOI: https://doi.org/10.1007/s10815-015-0559-2

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