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Effects of Trichostatin A on Cumulus Expansion during Mouse Oocyte Maturation

  • Du, Ming (Key Laboratory of Animal Genetics, Breeding and Reproduction,Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University) ;
  • Fu, Xiangwei (Key Laboratory of Animal Genetics, Breeding and Reproduction,Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University) ;
  • Zhou, Yanhua (Key Laboratory of Animal Genetics, Breeding and Reproduction,Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University) ;
  • Zhu, Shien (Key Laboratory of Animal Genetics, Breeding and Reproduction,Ministry of Agriculture and National Engineering Laboratory for Animal Breeding, College of Animal Science and Technology, China Agricultural University)
  • Received : 2013.02.28
  • Accepted : 2013.04.08
  • Published : 2013.11.01

Abstract

This study was conducted to investigate the effects of Trichostatin A (TSA) on cumulus expansion during mouse oocyte maturation. TSA treatment inhibited cumulus expansion and significantly reduced the cumulus expansion index (CEI) (p<0.05). To determine the underlying mechanism, the expression levels of several key factors that play crucial roles in cumulus expansion including components of extracellular matrix (ECM) (Has2, Ptgs2, Ptx3, and Tnfaip6) and Growth differentiation factor 9 (GDF9) were measured in control and TSA treated samples by real-time PCR. The effect of TSA on ERK phosphorylation (p-ERK1/2) in cumulus cells and GDF9 protein level in fully grown oocytes (FGOs) were detected by Western blotting. The expression levels of the ECM genes were significantly decreased (p<0.05) by TSA treatment while GDF9 expression did not response to TSA (p>0.05). TSA treatment blocked the activation of ERK1/2 (p<0.05) and had no significant effect on GDF9 protein expression (p>0.05). Collectively, these results suggested that TSA treatment altered ECM gene expression and blocked ERK1/2 activation to inhibit cumulus expansion in the mouse.

Keywords

Mouse;Cumulus-oocyte Complex;Cumulus Expansion;TSA

Acknowledgement

Supported by : National Natural Science Foundation

References

  1. Baker, A. H., D. R. Edwards, and G. Murphy. 2002. Metalloproteinase inhibitors: Biological actions and therapeutic opportunities. J. Cell Sci. 115:3719-3727. https://doi.org/10.1242/jcs.00063
  2. Barter, M. J., L. Pybus, G. J. Litherland, A. D. Rowan, I. M. Clark, D. R. Edwards, T. E. Cawston, and D. A. Young. 2010. Hdac-mediated control of erk- and pi3k-dependent tgf-beta-induced extracellular matrix-regulating genes. Matrix Biol. 29:602-612. https://doi.org/10.1016/j.matbio.2010.05.002
  3. Brush, M. H., A. Guardiola, J. H. Connor, T. P. Yao, and S. Shenolikar. 2004. Deactylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases. J. Biol. Chem. 279:7685-7691. https://doi.org/10.1074/jbc.M310997200
  4. Buccione, R., B. C. Vanderhyden, P. J. Caron, and J. J. Eppig. 1990. Fsh-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Dev. Biol. 138:16-25. https://doi.org/10.1016/0012-1606(90)90172-F
  5. Camaioni, A., V. C. Hascall, M. Yanagishita, and A. Salustri. 1993. Effects of exogenous hyaluronic acid and serum on matrix organization and stability in the mouse cumulus cell-oocyte complex. J. Biol. Chem. 268:20473-20481.
  6. Chen, L., P. T. Russell, and W. J. Larsen. 1993. Functional significance of cumulus expansion in the mouse: Roles for the preovulatory synthesis of hyaluronic acid within the cumulus mass. Mol. Reprod. Dev. 34:87-93. https://doi.org/10.1002/mrd.1080340114
  7. Dong, J., D. F. Albertini, K. Nishimori, T. R. Kumar, N. Lu, and M. M. Matzuk. 1996. Growth differentiation factor-9 is required during early ovarian folliculogenesis. Nature 383:531-535. https://doi.org/10.1038/383531a0
  8. Dragovic, R. A., L. J. Ritter, S. J. Schulz, F. Amato, D. T. Armstrong, and R. B. Gilchrist. 2005. Role of oocyte-secreted growth differentiation factor 9 in the regulation of mouse cumulus expansion. Endocrinology 146:2798-2806. https://doi.org/10.1210/en.2005-0098
  9. Dragovic, R. A., L. J. Ritter, S. J. Schulz, F. Amato, J. G. Thompson, D. T. Armstrong, and R. B. Gilchrist. 2007. Oocyte-secreted factor activation of smad 2/3 signaling enables initiation of mouse cumulus cell expansion. Biol. Reprod. 76:848-857. https://doi.org/10.1095/biolreprod.106.057471
  10. Elvin, J. A., A. T. Clark, P. Wang, N. M. Wolfman, and M. M. Matzuk. 1999. Paracrine actions of growth differentiation factor-9 in the mammalian ovary. Mol. Endocrinol. 13:1035-1048. https://doi.org/10.1210/me.13.6.1035
  11. Fagbohun, C. F. and S. M. Downs. 1990. Maturation of the mouse oocyte-cumulus cell complex: Stimulation by lectins. Biol. Reprod. 42:413-423. https://doi.org/10.1095/biolreprod42.3.413
  12. Fulop, C., S. Szanto, D. Mukhopadhyay, T. Bardos, R. V. Kamath, M. S. Rugg, A. J. Day, A. Salustri, V. C. Hascall, T. T. Glant, and K. Mikecz. 2003. Impaired cumulus mucification and female sterility in tumor necrosis factor-induced protein-6 deficient mice. Development 130:2253-2261. https://doi.org/10.1242/dev.00422
  13. Gui, L. M. and I. M. Joyce. 2005. Rna interference evidence that growth differentiation factor-9 mediates oocyte regulation of cumulus expansion in mice. Biol. Reprod. 72:195-199. https://doi.org/10.1095/biolreprod.104.033357
  14. Hayashi, M., E. A. McGee, G. Min, C. Klein, U. M. Rose, M. van Duin, and A. J. Hsueh. 1999. Recombinant growth differentiation factor-9 (gdf-9) enhances growth and differentiation of cultured early ovarian follicles. Endocrinology 140:1236-1244. https://doi.org/10.1210/en.140.3.1236
  15. Lim, H., B. C. Paria, S. K. Das, J. E. Dinchuk, R. Langenbach, J. M. Trzaskos, and S. K. Dey. 1997. Multiple female reproductive failures in cyclooxygenase 2-deficient mice. Cell. 91:197-208. https://doi.org/10.1016/S0092-8674(00)80402-X
  16. McPherron, A. C. and S. J. Lee. 1993. Gdf-3 and gdf-9: Two new members of the transforming growth factor-beta superfamily containing a novel pattern of cysteines. J. Biol. Chem. 268:3444-3449.
  17. Mukhopadhyay, D., A. Asari, M. S. Rugg, A. J. Day, and C. Fulop. 2004. Specificity of the tumor necrosis factor-induced protein 6-mediated heavy chain transfer from inter-alpha-trypsin inhibitor to hyaluronan: Implications for the assembly of the cumulus extracellular matrix. J. Biol. Chem. 279:11119-11128. https://doi.org/10.1074/jbc.M313471200
  18. Mulholland, N. M., E. Soeth, and C. L. Smith. 2003. Inhibition of mmtv transcription by hdac inhibitors occurs independent of changes in chromatin remodeling and increased histone acetylation. Oncogene 22:4807-4818. https://doi.org/10.1038/sj.onc.1206722
  19. Nair, A. R., L. J. Boersma, L. Schiltz, M. A. Chaudhry, and R. J. Muschel. 2001. Paradoxical effects of trichostatin a: Inhibition of nf-y-associated histone acetyltransferase activity, phosphorylation of hgcn5 and downregulation of cyclin a and b1 mrna. Cancer Lett. 166:55-64. https://doi.org/10.1016/S0304-3835(01)00418-9
  20. Ochsner, S. A., A. J. Day, M. S. Rugg, R. M. Breyer, R. H. Gomer, and J. S. Richards. 2003. Disrupted function of tumor necrosis factor-alpha-stimulated gene 6 blocks cumulus cell-oocyte complex expansion. Endocrinology 144:4376-4384. https://doi.org/10.1210/en.2003-0487
  21. Pujuguet, P., D. Radisky, D. Levy, C. Lacza, and M. J. Bissell. 2001. Trichostatin a inhibits beta-casein expression in mammary epithelial cells. J. Cell Biochem. 83:660-670. https://doi.org/10.1002/jcb.1260
  22. Salustri, A., C. Garlanda, E. Hirsch, M. De Acetis, A. Maccagno, B. Bottazzi, A. Doni, A. Bastone, G. Mantovani, P. P. Beck, G. Salvatori, D. J. Mahoney, A. J. Day, G. Siracusa, L. Romani, and A. Mantovani. 2004. Ptx3 plays a key role in the organization of the cumulus oophorus extracellular matrix and in in vivo fertilization. Development 131:1577-1586. https://doi.org/10.1242/dev.01056
  23. Saunders, N., A. Dicker, C. Popa, S. Jones, and A. Dahler. 1999. Histone deacetylase inhibitors as potential anti-skin cancer agents. Cancer Res. 59:399-404.
  24. Su, Y. Q., J. M. Denegre, K. Wigglesworth, F. L. Pendola, M. J. O'Brien, and J. J. Eppig. 2003. Oocyte-dependent activation of mitogen-activated protein kinase (erk1/2) in cumulus cells is required for the maturation of the mouse oocyte-cumulus cell complex. Dev. Biol. 263:126-138. https://doi.org/10.1016/S0012-1606(03)00437-8
  25. Su, Y. Q., S. Rubinstein, A. Luria, Y. Lax, and H. Breitbart. 2001. Involvement of mek-mitogen-activated protein kinase pathway in follicle-stimulating hormone-induced but not spontaneous meiotic resumption of mouse oocytes. Biol. Reprod. 65:358-365. https://doi.org/10.1095/biolreprod65.2.358
  26. Su, Y. Q., K. Sugiura, K. Wigglesworth, M. J. O'Brien, J. P. Affourtit, S. A. Pangas, M. M. Matzuk, and J. J. Eppig. 2008. Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: Bmp15 and gdf9 control cholesterol biosynthesis in cumulus cells. Development 135:111-121.
  27. Su, Y. Q., K. Sugiura, Y. Woo, K. Wigglesworth, S. Kamdar, J. Affourtit, and J. J. Eppig. 2007. Selective degradation of transcripts during meiotic maturation of mouse oocytes. Dev. Biol. 302:104-117. https://doi.org/10.1016/j.ydbio.2006.09.008
  28. Su, Y. Q., K. Wigglesworth, F. L. Pendola, M. J. O'Brien, and J. J. Eppig. 2002. Mitogen-activated protein kinase activity in cumulus cells is essential for gonadotropin-induced oocyte meiotic resumption and cumulus expansion in the mouse. Endocrinology 143:2221-2232. https://doi.org/10.1210/en.143.6.2221
  29. Suo, L., Q. G. Meng, Y. Pei, C. L. Yan, X. W. Fu, T. D. Bunch, and S. E. Zhu. 2010. Changes in acetylation on lysine 12 of histone h4 (ach4k12) of murine oocytes during maternal aging may affect fertilization and subsequent embryo development. Fertil. Steril. 93:945-951. https://doi.org/10.1016/j.fertnstert.2008.12.128
  30. Tsuji, N., M. Kobayashi, K. Nagashima, Y. Wakisaka, and K. Koizumi. 1976. A new antifungal antibiotic, trichostatin. J. Antibiot (Tokyo). 29:1-6. https://doi.org/10.7164/antibiotics.29.1
  31. Vanderhyden, B. C., P. J. Caron, R. Buccione, and J. J. Eppig. 1990. Developmental pattern of the secretion of cumulus expansion-enabling factor by mouse oocytes and the role of oocytes in promoting granulosa cell differentiation. Dev. Biol. 140:307-317. https://doi.org/10.1016/0012-1606(90)90081-S
  32. Vanderhyden, B. C., E. E. Telfer, and J. J. Eppig. 1992. Mouse oocytes promote proliferation of granulosa cells from preantral and antral follicles in vitro. Biol. Reprod. 46:1196-1204. https://doi.org/10.1095/biolreprod46.6.1196
  33. Varani, S., J. A. Elvin, C. Yan, J. DeMayo, F. J. DeMayo, H. F. Horton, M. C. Byrne, and M. M. Matzuk. 2002. Knockout of pentraxin 3, a downstream target of growth differentiation factor-9, causes female subfertility. Mol. Endocrinol. 16:1154-1167. https://doi.org/10.1210/me.16.6.1154
  34. Xu, W. S., R. B. Parmigiani, and P. A. Marks. 2007. Histone deacetylase inhibitors: Molecular mechanisms of action. Oncogene 26:5541-5552. https://doi.org/10.1038/sj.onc.1210620