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RFD is the official journal of the International Embryo Transfer Society and the Society for Reproductive Biology.


 

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Oxygen-regulated gene expression in murine cumulus cells

Karen L. Kind A B E , Kimberley K. Y. Tam A C , Kelly M. Banwell A C , Ashley D. Gauld A C , Darryl L. Russell A C , Anne M. Macpherson A C , Hannah M. Brown A C , Laura A. Frank A C , Daniel J. Peet D and Jeremy G. Thompson A C

A The Robinson Institute, Research Centre for Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
B School of Animal and Veterinary Sciences, University of Adelaide, Adelaide, SA 5005, Australia.
C School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
D School of Molecular and Biomedical Science, University of Adelaide, Adelaide, SA 5005, Australia.
E Corresponding author. Email: karen.kind@adelaide.edu.au

Reproduction, Fertility and Development - http://dx.doi.org/10.1071/RD13249
Submitted: 5 August 2013  Accepted: 15 November 2013   Published online: 6 January 2014


 
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Abstract

Oxygen is an important component of the environment of the cumulus–oocyte complex (COC), both in vivo within the ovarian follicle and during in vitro oocyte maturation (IVM). Cumulus cells have a key role in supporting oocyte development, and cumulus cell function and gene expression are known to be altered when the environment of the COC is perturbed. Oxygen-regulated gene expression is mediated through the actions of the transcription factors, the hypoxia-inducible factors (HIFs). In the present study, the effect of oxygen on cumulus cell gene expression was examined following in vitro maturation of the murine COC at 2%, 5% or 20% oxygen. Increased expression of HIF-responsive genes, including glucose transporter-1, lactate dehydrogenase A and BCL2/adenovirus E1B interacting protein 3, was observed in cumulus cells matured at 2% or 5%, compared with 20% oxygen. Stabilisation of HIF1α protein in cumulus cells exposed to low oxygen was confirmed by western blot and HIF-mediated transcriptional activity was demonstrated using a transgenic mouse expressing green fluorescent protein under the control of a promoter containing hypoxia response elements. These results indicate that oxygen concentration influences cumulus cell gene expression and support a role for HIF1α in mediating the cumulus cell response to varying oxygen.

Additional keywords: hypoxia inducible factors, oocyte.


References

Albertini, D. F., Combelles, C. M. H., Benecchi, E., and Carabatsos, M. J. (2001). Cellular basis for paracrine regulation of ovarian follicle development. Reproduction 121, 647–653.
CrossRef | CAS | PubMed |

Assou, S., Haouzi, D., De Vos, J., and Hamamah, S. (2010). Human cumulus cells as biomarkers for embryo and pregnancy outcomes. Mol. Hum. Reprod. 16, 531–538.
CrossRef | CAS | PubMed |

Banwell, K. M., Lane, M., Russell, D. L., Kind, K. L., and Thompson, J. G. (2007). Oxygen concentration during mouse oocyte in vitro maturation affects embryo and fetal development. Hum. Reprod. 22, 2768–2775.
CrossRef | CAS | PubMed |

Bekeredjian, R., Walton, C. B., MacCannell, K. A., Ecker, J., Kruse, F., Outten, J. T., Sutcliffe, D., Gerard, R. D., Bruick, R. K., and Shohet, R. V. (2010). Conditional HIF-1a expression produces a reversible cardiomyopathy. PLoS ONE 5, e11693.
CrossRef | PubMed |

Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouyssegur, J., and Mazure, N. M. (2009). Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domain. Mol. Cell. Biol. 29, 2570–2581.
CrossRef | CAS | PubMed |

Bermejo-Álvarez, P., Lonergan, P., Rizos, D., and Gutiérrez-Adan, A. (2010). Low oxygen tension during IVM improves bovine oocyte competence and enhances anaerobic glycolysis. Reprod. Biomed. Online 20, 341–349.
CrossRef | PubMed |

Bilton, R. L., and Booker, G. W. (2003). The subtle side to hypoxia-inducible factor (HIFalpha) regulation. Eur. J. Biochem. 270, 791–798.
CrossRef | CAS | PubMed |

Bontekoe, S., Mantikou, E., van Wely, M., Seshadri, S., Repping, S., and Mastenbroek, S. (2012). Low oxygen concentrations for embryo culture in assisted reproductive technologies (Review). Cochrane Database Syst. Rev. 11, CD008950.
CrossRef |

Boström, P., Magnusson, B., Svensson, P. A., Wiklund, O., Borén, J., Carlsson, L. M. S., Ståhlman, M., Olofsson, S. O., and Hultén, L. M. (2006). Hypoxia converts human macrophages into triglyceride-loaded foam cells. Arterioscler. Thromb. Vasc. Biol. 26, 1871–1876.
CrossRef | PubMed |

Bruick, R. K. (2000). Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97, 9082–9087.
CrossRef | CAS | PubMed |

Chen, G., Ray, R., Dubik, D., Shi, L., Cizeau, J., Bleackley, R. C., Saxena, S., Gietz, R. D., and Greenberg, A. H. (1997). The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis. J. Exp. Med. 186, 1975–1983.
CrossRef | CAS | PubMed |

Chen, B., Nelson, D. M., and Sadovsky, Y. (2006). N-Myc down-regulated gene 1 modulates the response of term human trophoblasts to hypoxic injury. J. Biol. Chem. 281, 2764–2772.
CrossRef | CAS | PubMed |

Chen, Z., Zhang, D., Yue, F., Zheng, M., Kovacevic, Z., and Richardson, D. R. (2012). The iron chelators Dp44mT and DFO inhibit TGF-β-induced epithelial–mesenchymal transition via up-regulation of N-Myc downstream-regulated gene 1 (NDRG1). J. Biol. Chem. 287, 17 016–17 028.
CrossRef | CAS |

Clark, A. R., Stokes, Y. M., Lane, M., and Thompson, J. G. (2006). Mathematical modelling of oxygen concentration in bovine and murine cumulus–oocyte complexes. Reproduction 131, 999–1006.
CrossRef | CAS | PubMed |

Dehne, N., and Brune, B. (2009). HIF-1 in the inflammatory microenvironment. Exp. Cell Res. 315, 1791–1797.
CrossRef | CAS | PubMed |

Déry, M.-A. C., Michaud, M. D., and Richard, D. E. (2005). Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int. J. Biochem. Cell Biol. 37, 535–540.
CrossRef |

Duncan, W. C., van den Driesche, S., and Fraser, H. M. (2008). Inhibition of vascular endothelial growth factor in the primate ovary up-regulates hypoxia-inducible factor-1α in the follicle and corpus luteum. Endocrinology 149, 3313–3320.
CrossRef | CAS | PubMed |

Dunning, K. R., Lane, M., Brown, H., Yeo, C., Robker, R. L., and Russell, D. L. (2007). Altered composition of the cumulus–oocyte complex matrix during in vitro maturation of oocytes. Hum. Reprod. 22, 2842–2850.
CrossRef | CAS | PubMed |

Ellen, T. P., Ke, Q., Zhang, P., and Costa, M. (2008). NRDG1, a growth- and cancer-related gene: regulation of gene expression and function in normal and diseased states. Carcinogenesis 29, 2–8.
CrossRef | CAS | PubMed |

Ema, M., Taya, S., Yokotani, N., Sogawa, K., Matsuda, Y., and Fujii-Kuriyama, Y. (1997). A novel bHLH-PAS factor with close sequence similarity to hypoxia-inducible factor 1alpha regulates the VEGF expression and is potentially involved in lung and vascular development. Proc. Natl. Acad. Sci. USA 94, 4273–4278.
CrossRef | CAS | PubMed |

Eppig, J. J. (1991). Intercommunication between mammalian oocytes and companion somatic cells. Bioessays 13, 569–574.
CrossRef | CAS | PubMed |

Flowers, M. T., and Ntambi, J. M. (2008). Role of stearoyl-coenzyme A desaturase in regulating lipid metabolism. Curr. Opin. Lipidol. 19, 248–256.
CrossRef | CAS | PubMed |

Gardner, D. K., and Lane, M. (1996). Alleviation of the 2-cell block and development to the blastocyst of CF1 mouse embryos: role of amino acids, EDTA and physical parameters. Hum. Reprod. 11, 2703–2712.
CrossRef | CAS | PubMed |

Gebhardt, K. M., Feil, D. K., Dunning, K. R., Lane, M., and Russell, D. L. (2011). Human cumulus cell gene expression as a biomarker of pregnancy outcome after single embryo transfer. Fertil. Steril. 96, 47–52.
CrossRef | CAS | PubMed |

Gradin, K., McGuire, J., Wenger, R. H., Kvietikova, I., Whitelaw, M. L., Toftgard, R., Tora, L., Gassmann, M., and Poellinger, L. (1996). Functional interference between hypoxia and dioxin signal transduction pathways: competition for recruitment of the Arnt transcription factor. Mol. Cell. Biol. 16, 5221–5231.
| CAS | PubMed |

Haidri, A. A., Miller, I. M., and Gwatkin, R. B. L. (1971). Culture of mouse oocytes in vitro, using a system without oil or protein. J. Reprod. Fertil. 26, 409–411.
CrossRef | CAS | PubMed |

Hashimoto, S. (2009). Application of in vitro maturation to assisted reproductive technology. J. Reprod. Dev. 55, 1–10.
CrossRef | CAS | PubMed |

Hashimoto, S., Minami, N., Takakura, R., Yamada, M., Imai, H., and Kashima, N. (2000). Low oxygen tension during in vitro maturation is beneficial for supporting the subsequent development of bovine cumulus-oocyte complexes. Mol. Reprod. Dev. 57, 353–360.
CrossRef | CAS | PubMed |

Höpfl, G., Ogunshola, O., and Gassmann, M. (2004). HIFs and tumours – causes and consequences. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R608–R623.
CrossRef | PubMed |

Huey, S., Abuhamad, A., Barroso, G., Hsu, M. I., Kolm, P., Mayer, J., and Oehninger, S. (1999). Perifollicular blood flow Doppler indices but not follicular pO2, pCO2 or pH, predict oocyte developmental competence in in vitro fertilisation. Fertil. Steril. 72, 707–712.
CrossRef | CAS | PubMed |

Igal, R. A. (2010). Stearoyl-CoA desaturase-1: a novel key player in the mechanisms of cell proliferation, programmed cell death and transformation to cancer. Carcinogenesis 31, 1509–1515.
CrossRef | CAS | PubMed |

Jakobsson, A., Westerberg, R., and Jacobsson, A. (2006). Fatty acid elongases in mammals: their regulation and roles in metabolism. Prog. Lipid Res. 45, 237–249.
CrossRef | CAS | PubMed |

Kim, J., Bagchi, I. C., and Bagchi, M. K. (2009). Signalling by hypoxia-inducible factors is critical for ovulation in mice. Endocrinology 150, 3392–3400.
CrossRef | CAS | PubMed |

Kind, K. L., Banwell, K. M., Gebhardt, K. M., Macpherson, A., Gauld, A., Russell, D. L., and Thompson, J. G. (2013). Microarray analysis of mRNA from cumulus cells following in vivo and in vitro maturation of mouse cumulus–oocyte complexes. Reprod. Fertil. Dev. 25, 426–438.
CrossRef | CAS | PubMed |

Li, J., Bosch-Marce, M., Nanayakkara, A., Savransky, V., Fried, S. K., Semenza, G. L., and Polotsky, V. Y. (2006). Altered metabolic responses to intermittent hypoxia in mice with partial deficiency of hypoxia-inducible factor-1α. Physiol. Genomics 25, 450–457.
CrossRef | CAS | PubMed |

Matsuzaka, T., and Shimano, H. (2009). Elovl6: a new player in fatty acid metabolism and insulin sensitivity. J. Mol. Med. 87, 379–384.
CrossRef | CAS | PubMed |

Mazure, N. M., and Pouyssegur, J. (2010). Hypoxia-induced autophagy: cell death or cell survival? Curr. Opin. Cell Biol. 22, 177–180.
CrossRef | CAS | PubMed |

Meintjes, M., Chantilis, S. J., Douglas, J. D., Rodriguez, A. J., Guerami, A. R., Bookout, D. M., Barnett, B. D., and Madden, J. D. (2009). A controlled randomised trial evaluating the effect of lowered incubator oxygen tension on live births in a predominantly blastocyst transfer program. Hum. Reprod. 24, 300–307.
CrossRef | PubMed |

Mellor, H. R., and Harris, A. L. (2007). The role of the hypoxia-inducible BH3-only proteins BNIP3 and BNIP3L in cancer. Cancer Metastasis Rev. 26, 553–566.
CrossRef | CAS | PubMed |

Melotte, V., Qu, X., Ongenaert, M., van Criekinge, W., de Bruine, A. P., Baldwin, H. S., and van Engeland, M. (2010). The N-myc downstream-regulated gene (NRDG) family: diverse functions, multiple application. FASEB J. 24, 4153–4166.
CrossRef | CAS | PubMed |

Pereira, M. M., Machado, M. A., Costa, F. Q., Serapiao, R. V., Viana, J. H. M., and Camargo, L. S. A. (2010). Effect of oxygen tension and serum during IVM on developmental competence of bovine oocytes. Reprod. Fertil. Dev. 22, 1074–1082.
CrossRef | PubMed |

Pinyopummintr, T., and Bavister, B. D. (1995). Optimum gas atmosphere for in vitro maturation and in vitro fertilisation of bovine oocytes. Theriogenology 44, 471–477.
CrossRef | CAS | PubMed |

Preis, K. A., Seidel, G. E., and Gardner, D. K. (2007). Reduced oxygen concentration improves the developmental competence of mouse oocytes following in vitro maturation. Mol. Reprod. Dev. 74, 893–903.
CrossRef | CAS | PubMed |

Pringle, K. G., Kind, K. L., Sferruzzi-Perri, A. N., Thompson, J. G., and Roberts, C. T. (2010). Beyond oxygen: complex regulation and activity of HIFs in pregnancy. Hum. Reprod. Update 16, 415–431.
CrossRef | CAS | PubMed |

Rankin, E.B., Rha, J., Selak, M.A., Unger, T.L., Keith, B., Liu, Q., and Haase, V.H. (2009). Hypoxia-inducible factor 2 regulates hepatic lipid metabolism. Mol. Cell. Biol. 29, 4527–4538.
CrossRef | CAS | PubMed |

Redding, G. P., Bronlund, J. E., and Hart, A. L. (2008). Theoretical investigation into the dissolved oxygen levels in follicular fluid of the developing human follicle using mathematical modelling. Reprod. Fertil. Dev. 20, 408–417.
CrossRef | CAS | PubMed |

Salnikow, K., Davidson, T., and Costa, M. (2002). The role of hypoxia-inducible signalling pathway in nickel carcinogenesis. Environ. Health Perspect. 110, 831–834.
CrossRef | CAS | PubMed |

Semenza, G. L. (2000). HIF-1: mediator of physiological and pathophysiological responses to hypoxia. J. Appl. Physiol. 88, 1474–1480.
| CAS | PubMed |

Semenza, G. L. (2010). Oxygen homeostasis. Wiley Interdiscip. Rev. Syst. Biol. Med. 2, 336–361.
CrossRef | CAS | PubMed |

Sutton-McDowall, M. L., Gilchrist, R. B., and Thompson, J. G. (2010). The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction 139, 685–695.
CrossRef | CAS | PubMed |

Tam, K. K. Y., Russell, D. L., Peet, D. J., Bracken, C. P., Rodgers, R. J., Thompson, J. G., and Kind, K. L. (2010). Hormonally regulated follicle differentiation and luteinisation in the mouse is associated with hypoxia-inducible factor activity. Mol. Cell. Endocrinol. 327, 47–55.
CrossRef | CAS |

Thompson, J. G., Simpson, A. C., Pugh, P. A., Donnelly, P. E., and Tervit, H. R. (1990). Effect of oxygen concentration on in vitro development of preimplantation sheep and cattle embryos. J. Reprod. Fertil. 89, 573–578.
CrossRef | CAS | PubMed |

Thompson, J. G., Lane, M., and Gilchrist, R. B. (2007). Metabolism of the bovine cumulus–oocyte complex and influence on subsequent developmental competence. Soc. Reprod. Fertil. Suppl. 64, 179–190.
| CAS | PubMed |

Uchida, T., Rossignol, F., Matthay, M. A., Mounier, R., Couette, S., Clottes, E., and Clerici, C. (2004). Prolonged hypoxia differentially regulates hypoxia-inducible factor (HIF)-1α and HIF-2α expression in lung epithelial cells. J. Biol. Chem. 279, 14 871–14 878.
CrossRef | CAS |

Van Blerkom, J., Antczak, M., and Schrader, R. (1997). The developmental potential of the human oocyte is related to the dissolved oxygen content of follicular fluid: association with vascular endothelial growth factor levels and perifollicular blood flow characteristics. Hum. Reprod. 12, 1047–1055.
CrossRef | CAS | PubMed |

van Montfoort, A. P. A., Geraedts, J. P. M., Dumoulin, J. C. M., Stassen, A. P. M., Evers, J. L. H., and Ayoubi, T. A. Y. (2008). Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis. Mol. Hum. Reprod. 14, 157–168.
CrossRef | CAS |

Waldenström, U., Engström, A. B., Hellberg, D., and Nilsson, S. (2009). Low-oxygen compared with high-oxygen atmosphere in blastocyst culture, a prospective randomised study. Fertil. Steril. 91, 2461–2465.
CrossRef | PubMed |

Wale, P. L., and Gardner, D. K. (2010). Time-lapse analysis of mouse embryo development in oxygen gradients. Reprod. Biomed. Online 21, 402–410.
CrossRef | CAS | PubMed |

Wenger, R. H. (2002). Cellular adaptation to hypoxia: O2 sensing protein hydroxylases, hypoxia-inducible transcription factors and O2-regulated gene expression. FASEB J. 16, 1151–1162.
CrossRef | CAS | PubMed |

Zhang, H., Bosch-Marce, M., Shimoda, L. A., Tan, Y. S., Baek, J. H., Wesley, J. B., Gonzalez, F. J., and Semenza, G. L. (2008). Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J. Biol. Chem. 283, 10 892–10 903.
CrossRef | CAS |


   
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