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Downregulation of gene expression and activity of GRIM-19 affects mouse oocyte viability, maturation, embryo development and implantation

  • Gamete Biology
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the expression of GRIM-19 (Gene associated with retinoid-interferon-induced mortality 19) in mouse oocytes and preimplantation embryos, and to study the effect of GRIM-19 on the developmental competence of mouse oocytes and embryos.

Methods

GRIM-19 was evaluated at both mRNA and protein levels. The expression of GRIM-19 gene was downregulated in mouse oocytes cultured in vitro by specific small interfering RNA (siRNA) injection, while the activity of GRIM-19 was decreased by microinjection of a GRIM-19 antibody into the cytoplasm of germinal vesicle (GV) oocytes. Oocytes matured in vitro were then fertilized by intracytoplasmic sperm injection (ICSI), followed by observation and evaluation of fertilization rate, cleavage rate, blastocyst formation rate and implantation rate.

Results

GRIM-19 is expressed throughout oocyte maturation and preimplantation embryo development stages. GRIM-19 was localized primarily in the cytoplasm of all cells examined. Downregulation of gene expression and activity of GRIM-19 resulted in decreased oocyte viability, potency of oocyte maturation, embryo development and implantation.

Conclusions

GRIM-19 may play important roles in mouse oogenesis and early embryonic development and implantation.

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References

  1. Duranthon V, Renard JP. The developmental competence of mammalian oocytes: a convenient but biologically fuzzy concept. Theriogenology. 2001;55(6):1277–89.

    Article  CAS  PubMed  Google Scholar 

  2. Sirard MA. Resumption of meiosis: mechanism involved in meiotic progression and its relation with developmental competence. Theriogenology. 2001;55(6):1241–54.

    Article  CAS  PubMed  Google Scholar 

  3. Krey LC, Grifo JA. Poor embryo quality: the answer lies (mostly) in the egg. Fertil Steril. 2001;75(3):466–8.

    Article  CAS  PubMed  Google Scholar 

  4. Jansen RP, Burton GJ. Mitochondrial dysfunction in reproduction. Mitochondrion. 2004;4(5–6):577–600.

    Article  CAS  PubMed  Google Scholar 

  5. Newmeyer DD, Ferguson-Miller S. Mitochondria: releasing power for life and unleashing the machineries of death. Cell. 2003;112(4):481–90.

    Article  CAS  PubMed  Google Scholar 

  6. Saraste M. Oxidative phosphorylation at the fin de siecle. Science. 1999;283(5407):1488–93.

    Article  CAS  PubMed  Google Scholar 

  7. Coenen MJ, van den Heuvel LP, Smeitink JA. Mitochondrial oxidative phosphorylation system assembly in man: recent achievements. Curr Opin Neurol. 2001;14(6):777–81.

    Article  CAS  PubMed  Google Scholar 

  8. McConnell JM, Petrie L. Mitochondrial DNA turnover occurs during preimplantation development and can be modulated by environmental factors. Reprod Biomed Online. 2004;9(4):418–24.

    Article  CAS  PubMed  Google Scholar 

  9. Cohen J, Scott R, Alikani M, Schimmel T, Munne S, Levron J, et al. Ooplasmic transfer in mature human oocytes. Mol Hum Reprod. 1998;4(3):269–80.

    Article  CAS  PubMed  Google Scholar 

  10. Dale B, Wilding M, Botta G, Rasile M, Marino M, Di Matteo L, et al. Pregnancy after cytoplasmic transfer in a couple suffering from idiopathic infertility: case report. Hum Reprod. 2001;16(7):1469–72.

    Article  CAS  PubMed  Google Scholar 

  11. Barritt JA, Brenner CA, Malter HE, Cohen J. Mitochondria in human offspring derived from ooplasmic transplantation. Hum Reprod. 2001;16(3):513–6.

    Article  CAS  PubMed  Google Scholar 

  12. El Shourbagy SH, Spikings EC, Freitas M, St John JC. Mitochondria directly influence fertilisation outcome in the pig. Reproduction. 2006;131(2):233–45.

    Article  PubMed  Google Scholar 

  13. Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV. Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon-beta and retinoic acid combination, using a genetic approach. J Biol Chem. 2000;275(43):33416–26.

    Article  CAS  PubMed  Google Scholar 

  14. Lufei C, Ma J, Huang G, Zhang T, Novotny-Diermayr V, Ong CT, et al. GRIM-19, a death-regulatory gene product, suppresses Stat3 activity via functional interaction. EMBO J. 2003;22(6):1325–35.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Zhang J, Yang J, Roy SK, Tininini S, Hu J, Bromberg JF, et al. The cell death regulator GRIM-19 is an inhibitor of signal transducer and activator of transcription 3. Proc Natl Acad Sci U S A. 2003;100(16):9342–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Maximo V, Botelho T, Capela J, Soares P, Lima J, Taveira A, et al. Somatic and germline mutation in GRIM-19, a dual function gene involved in mitochondrial metabolism and cell death, is linked to mitochondrion-rich (Hurthle cell) tumours of the thyroid. Br J Cancer. 2005;92(10):1892–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE, Hirst J. GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH: ubiquinone oxidoreductase (complex I). J Biol Chem. 2001;276(42):38345–8.

    Article  CAS  PubMed  Google Scholar 

  18. Huang G, Lu H, Hao A, Ng DC, Ponniah S, Guo K, et al. GRIM-19, a cell death regulatory protein, is essential for assembly and function of mitochondrial complex I. Mol Cell Biol. 2004;24(19):8447–56.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Huang G, Chen Y, Lu H, Cao X. Coupling mitochondrial respiratory chain to cell death: an essential role of mitochondrial complex I in the interferon-beta and retinoic acid-induced cancer cell death. Cell Death Differ. 2007;14(2):327–37.

    Article  CAS  PubMed  Google Scholar 

  20. Mamo S, Gal AB, Bodo S, Dinnyes A. Quantitative evaluation and selection of reference genes in mouse oocytes and embryos cultured in vivo and in vitro. BMC Dev Biol. 2007;7:14.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Jeong YJ, Choi HW, Shin HS, Cui XS, Kim NH, Gerton GL, et al. Optimization of real time RT-PCR methods for the analysis of gene expression in mouse eggs and preimplantation embryos. Mol Reprod Dev. 2005;71(3):284–9.

    Article  CAS  PubMed  Google Scholar 

  22. Dai Y, Lee C, Hutchings A, Sun Y, Moor R. Selective requirement for Cdc25C protein synthesis during meiotic progression in porcine oocytes. Biol Reprod. 2000;62(3):519–32.

    Article  CAS  PubMed  Google Scholar 

  23. Stewart BM, Block J, Morelli P, Navarette AE, Amstalden M, Bonilla L et al. Efficacy of embryo transfer in lactating dairy cows during summer using fresh or vitrified embryos produced in vitro with sex-sorted semen. J Dairy Sci 94(7):3437–45

  24. Yamagata K, Suetsugu R, Wakayama T. Assessment of chromosomal integrity using a novel live-cell imaging technique in mouse embryos produced by intracytoplasmic sperm injection. Hum Reprod. 2009;24(10):2490–9.

    Article  CAS  PubMed  Google Scholar 

  25. Yamagata K, Suetsugu R, Wakayama T. Long-term, six-dimensional live-cell imaging for the mouse preimplantation embryo that does not affect full-term development. J Reprod Dev. 2009;55(3):343–50.

    Article  PubMed  Google Scholar 

  26. Ohta H, Sakaide Y, Wakayama T. Long-term preservation of mouse spermatozoa as frozen testicular sections. J Reprod Dev. 2008;54(4):295–8.

    Article  PubMed  Google Scholar 

  27. Hiendleder S, Wolf E. The mitochondrial genome in embryo technologies. Reprod Domest Anim. 2003;38(4):290–304.

    Article  CAS  PubMed  Google Scholar 

  28. Kondo I, Suganuma N, Ando T, Asada Y, Furuhashi M, Tomoda Y. Clinical factors for successful cryopreserved-thawed embryo transfer. J Assist Reprod Genet. 1996;13(3):201–6.

    Article  CAS  PubMed  Google Scholar 

  29. Stojkovic M, Machado SA, Stojkovic P, Zakhartchenko V, Hutzler P, Goncalves PB, et al. Mitochondrial distribution and adenosine triphosphate content of bovine oocytes before and after in vitro maturation: correlation with morphological criteria and developmental capacity after in vitro fertilization and culture. Biol Reprod. 2001;64(3):904–9.

    Article  CAS  PubMed  Google Scholar 

  30. Carroll J, Fearnley IM, Skehel JM, Shannon RJ, Hirst J, Walker JE. Bovine complex I is a complex of 45 different subunits. J Biol Chem. 2006;281(43):32724–7.

    Article  CAS  PubMed  Google Scholar 

  31. Murray J, Zhang B, Taylor SW, Oglesbee D, Fahy E, Marusich MF, et al. The subunit composition of the human NADH dehydrogenase obtained by rapid one-step immunopurification. J Biol Chem. 2003;278(16):13619–22.

    Article  CAS  PubMed  Google Scholar 

  32. Sakkas D, Shoukir Y, Chardonnens D, Bianchi PG, Campana A. Early cleavage of human embryos to the two-cell stage after intracytoplasmic sperm injection as an indicator of embryo viability. Hum Reprod. 1998;13(1):182–7.

    Article  CAS  PubMed  Google Scholar 

  33. Van Royen E, Mangelschots K, De Neubourg D, Valkenburg M, Van de Meerssche M, Ryckaert G, et al. Characterization of a top quality embryo, a step towards single-embryo transfer. Hum Reprod. 1999;14(9):2345–9.

    Article  PubMed  Google Scholar 

  34. Scott L, Alvero R, Leondires M, Miller B. The morphology of human pronuclear embryos is positively related to blastocyst development and implantation. Hum Reprod. 2000;15(11):2394–403.

    Article  CAS  PubMed  Google Scholar 

  35. Eichenlaub-Ritter U, Vogt E, Yin H, Gosden R. Spindles, mitochondria and redox potential in ageing oocytes. Reprod Biomed Online. 2004;8(1):45–58.

    Article  CAS  PubMed  Google Scholar 

  36. Lee SH, Han JH, Cho SW, Cha KE, Park SE, Cha KY. Mitochondrial ATPase 6 gene expression in unfertilized oocytes and cleavage-stage embryos. Fertil Steril. 2000;73(5):1001–5.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (grant number 81370711), National Natural Science Foundation of China (grant number 30901603), Doctor Foundation of Shandong Province (grant number BS2009SW031), and Shandong Family Planning Commission Foundation (grant number 2009–8).

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Correspondence to Xiaohui Deng.

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Chao, L., Wang, X., Yang, Y. et al. Downregulation of gene expression and activity of GRIM-19 affects mouse oocyte viability, maturation, embryo development and implantation. J Assist Reprod Genet 32, 461–470 (2015). https://doi.org/10.1007/s10815-014-0413-y

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  • DOI: https://doi.org/10.1007/s10815-014-0413-y

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