Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Etv5, a transcription factor with versatile functions in male reproduction

  • Eo, Jinwon (Department of Biomedical Science and Technology, Konkuk University) ;
  • Song, Haengseok (Department of Biomedical Science, CHA University) ;
  • Lim, Hyunjung Jade (Department of Biomedical Science and Technology, Konkuk University)
  • Received : 2012.05.21
  • Accepted : 2012.06.08
  • Published : 2012.06.30
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Abstract

Transcription factors govern diverse aspects of cell growth and differentiation as major switches of gene expression. Etv5, a member of the E26 transformation-specific family of transcription factors, has many stories to share when it comes to reproduction. Etv5 deficient mice show complex infertility phenotypes both in males and females. In males, the infertility phenotype exhibited by Etv5 deficiency is sexually dimorphic, and it involves both somatic cells and germ cells. In $Etv5^{-/-}$ female mice, the problem is more complicated by hormonal involvement. This review synthesizes old and new information on this versatile transcription factor-from the inadvertent discovery of its role in the testes to its newly discovered role in maintaining spermatogonial stem cells.

Keywords

Acknowledgement

Supported by : Konkuk University

References

  1. Sharrocks AD. The ETS-domain transcription factor family. Nat Rev Mol Cell Biol 2001;2:827-37.
  2. Oikawa T, Yamada T. Molecular biology of the Ets family of transcription factors. Gene 2003;303:11-34.
  3. Oh S, Shin S, Janknecht R. ETV1, 4 and 5: an oncogenic subfamily of ETS transcription factors. Biochim Biophys Acta 2012;1826:1-12.
  4. Jeon IS, Shapiro DN. Phylogenetically interrelated ETS genes, ETV1, ERM and E1A-F locate on different chromosomes. J Korean Med Sci 1998;13:355-60.
  5. Monté D, Baert JL, Defossez PA, de Launoit Y, Stéhelin D. Molecular cloning and characterization of human ERM, a new member of the Ets family closely related to mouse PEA3 and ER81 transcription factors. Oncogene 1994;9:1397-406.
  6. Coutte L, Monté D, Imai K, Pouilly L, Dewitte F, Vidaud M, et al. Characterization of the human and mouse ETV1/ER81 transcription factor genes: role of the two alternatively spliced isoforms in the human. Oncogene 1999;18:6278-86.
  7. Howe LR, Crawford HC, Subbaramaiah K, Hassell JA, Dannenberg AJ, Brown AM. PEA3 is up-regulated in response to Wnt1 and activates the expression of cyclooxygenase-2. J Biol Chem 2001;276:20108-15.
  8. Rorth P, Nerlov C, Blasi F, Johnsen M. Transcription factor PEA3 participates in the induction of urokinase plasminogen activator transcription in murine keratinocytes stimulated with epidermal growth factor or phorbol-ester. Nucleic Acids Res 1990;18:5009-17.
  9. Crawford HC, Fingleton B, Gustavson MD, Kurpios N, Wagenaar RA, Hassell JA, et al. The PEA3 subfamily of Ets transcription factors synergizes with beta-catenin-LEF-1 to activate matrilysin transcription in intestinal tumors. Mol Cell Biol 2001;21:1370-83.
  10. Levallet J, Koskimies P, Rahman N, Huhtaniemi I. The promoter of murine follicle-stimulating hormone receptor: functional characterization and regulation by transcription factor steroidogenic factor 1. Mol Endocrinol 2001;15:80-92.
  11. El-Tanani M, Platt-Higgins A, Rudland PS, Campbell FC. Ets gene PEA3 cooperates with beta-catenin-Lef-1 and c-Jun in regulation of osteopontin transcription. J Biol Chem 2004;279:20794-806.
  12. Eo J, Han K, K MM, Song H, Lim HJ. Etv5, an ETS transcription factor, is expressed in granulosa and cumulus cells and serves as a transcriptional regulator of the cyclooxygenase-2. J Endocrinol 2008;198:281-90.
  13. Bartel FO, Higuchi T, Spyropoulos DD. Mouse models in the study of the Ets family of transcription factors. Oncogene 2000;19:6443-54.
  14. Maroulakou IG, Bowe DB. Expression and function of Ets transcription factors in mammalian development: a regulatory network. Oncogene 2000;19:6432-42.
  15. Chotteau-Lelièvre A, Desbiens X, Pelczar H, Defossez PA, de Launoit Y. Differential expression patterns of the PEA3 group transcription factors through murine embryonic development. Oncogene 1997;15:937-52.
  16. Arber S, Ladle DR, Lin JH, Frank E, Jessell TM. ETS gene Er81 controls the formation of functional connections between group Ia sensory afferents and motor neurons. Cell 2000;101:485-98.
  17. Laing MA, Coonrod S, Hinton BT, Downie JW, Tozer R, Rudnicki MA, et al. Male sexual dysfunction in mice bearing targeted mutant alleles of the PEA3 Ets gene. Mol Cell Biol 2000;20:9337-45.
  18. Chen C, Ouyang W, Grigura V, Zhou Q, Carnes K, Lim H, et al. ERM is required for transcriptional control of the spermatogonial stem cell niche. Nature 2005;436:1030-4.
  19. Xin JH, Cowie A, Lachance P, Hassell JA. Molecular cloning and characterization of PEA3, a new member of the Ets oncogene family that is differentially expressed in mouse embryonic cells. Genes Dev 1992;6:481-96.
  20. Schlesser HN, Simon L, Hofmann MC, Murphy KM, Murphy T, Hess RA, et al. Effects of ETV5 [ets variant gene 5] on testis andbody growth, time course of spermatogonial stem cell loss, and fertility in mice. Biol Reprod 2008;78:483-9.
  21. Eo J, Shin H, Kwon S, Song H, Murphy KM, Lim JH. Complex ovarian defects lead to infertility in Etv5-/- female mice. Mol Hum Reprod 2011;17:568-76.
  22. Morrow CM, Tyagi G, Simon L, Carnes K, Murphy KM, Cooke PS, et al. Claudin 5 expression in mouse seminiferous epithelium is dependent upon the transcription factor ets variant 5 and contributes to blood-testis barrier function. Biol Reprod 2009;81: 871-9.
  23. Simon L, Ekman GC, Garcia T, Carnes K, Zhang Z, Murphy T, et al. ETV5 regulates sertoli cell chemokines involved in mouse stem/ progenitor spermatogonia maintenance. Stem Cells 2010;28:1882-92.
  24. Tyagi G, Carnes K, Morrow C, Kostereva NV, Ekman GC, Meling DD, et al. Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis. Biol Reprod 2009;81:258-66.
  25. Meng X, Lindahl M, Hyvonen ME, Parvinen M, de Rooij DG, Hess MW, et al. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 2000;287:1489-93.
  26. Kanatsu-Shinohara M, Ogonuki N, Iwano T, Lee J, Kazuki Y, Inoue K, et al. Genetic and epigenetic properties of mouse male germline stem cells during long-term culture. Development 2005;132:4155-63.
  27. Kubota H, Avarbock MR, Brinster RL. Growth factors essential for self-renewal and expansion of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 2004;101:16489-94.
  28. Wu X, Goodyear SM, Tobias JW, Avarbock MR, Brinster RL. Spermatogonial stem cell self-renewal requires ETV5-mediated downstream activation of Brachyury in mice. Biol Reprod 2011;85:1114-23.
  29. Ishii K, Kanatsu-Shinohara M, Toyokuni S, Shinohara T. FGF2 mediates mouse spermatogonial stem cell self-renewal via upregulation of Etv5 and Bcl6b through MAP2K1 activation. Development 2012;139:1734-43.
  30. Niu Z, Goodyear SM, Rao S, Wu X, Tobias JW, Avarbock MR, et al. MicroRNA-21 regulates the self-renewal of mouse spermatogonial stem cells. Proc Natl Acad Sci U S A 2011;108:12740-5.
  31. Costantini F. GDNF/Ret signaling and renal branching morphogenesis: From mesenchymal signals to epithelial cell behaviors. Organogenesis 2010;6:252-62.
  32. Lu BC, Cebrian C, Chi X, Kuure S, Kuo R, Bates CM, et al. Etv4 and Etv5 are required downstream of GDNF and Ret for kidney branching morphogenesis. Nat Genet 2009;41:1295-302.
  33. Kawamura K, Ye Y, Kawamura N, Jing L, Groenen P, Gelpke MS, et al. Completion of Meiosis I of preovulatory oocytes and facilitation of preimplantation embryo development by glial cell linederived neurotrophic factor. Dev Biol 2008;315:189-202.

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