Abstract
Mammalian development occurs in the hypoxic environment of the uterus (1,2). Initially, the limited oxygen available can adequately diffuse to all the cells of the growing conceptus. However, with continued growth, diffusion becomes less efficient and results in a “physiologic hypoxia” within the embryo (3). Current models suggest this physiologic hypoxia acts as a stimulus to coordinate the development of the cardiovascular system. Once formed, oxygen can be transported throughout the organism to enable aerobic respiration and promote increased ATP production. Unless the increasing energy demands of the embryo are met, further development will be halted, and early lethality will occur.
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References
Rodesch, F., Simon, P., Donner, C, and Jauniaux, E. (1992) Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy. Obstet. Gynecol. 80, 283–285.
Fischer, B. and Bavister, B. D. (1993) Oxygen tension in the oviduct and uterus of rhesus monkeys, hamsters and rabbits. J. Reprod. Fertil. 99, 673–679.
Maltepe, E. and Simon, M. C. (1998) Oxygen, genes, and development: an analysis of the role of hypoxic gene regulation during murine vascular development. J. Mol. Med. 76, 391–401.
Kozak, K. R., Abbott, B., and Hankinson, O. (1997) ARNT-deficient mice and placental differentiation. Dev. Biol. 191, 297–305.
Maltepe, E., Schmidt, J. V., Baunoch, D., Bradfield, C. A., and Simon, M. C. (1997) Abnormal angiogenesis and responses to glucose and oxygen deprivation in mice lacking the protein ARNT. Nature 386, 403–407.
Carmeliet, P., Dor, Y., Herbert, J. M., Fukumura, D., Brusselmans, K., Dewerchin, M., et al. (1998) Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394, 485–490.
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., et al. (1998) Cellular and developmental control of O2 homeostasis by hypoxia-inducible factor 1 alpha. Genes Dev. 12, 149–162.
Ryan, H. E., Lo, J., and Johnson, R. S. (1998) HIF-1a is required for solid tumor formation and embryonic vascularization. EMBO J. 17, 3005–3015.
Adelman, D. M., Maltepe, E., and Simon, M. C. (1999) Multilineage embryonic hematopoiesis requires hypoxic ARNT activity. Genes Dev. 13, 2478–2483.
Adelman, D. M., Gertsenstein, M., Nagy, A., Simon, M. C., and Maltepe, E. (2000) Placental cell fates are regulated in vivo by HIF-mediated hypoxia responses. Genes Dev. 14, 3191–3203.
Gassmann, M., Fandrey, J., Bichet, S., Wartenberg, M., Marti, H. H., Bauer, C., et al. (1996) Oxygen supply and oxygen-dependent gene expression in differentiating embryonic stem cells. Proc. Natl. Acad. Sci. USA 93, 2867–2872.
Tanaka, S., Kunath, T., Hadjantonakis, A. K., Nagy, A., and Rossant, J. (1998) Promotion of trophoblast stem cell proliferation by FGF4. Science 282, 2072–2075.
Adelman, D. M. and Simon, M. C. (2000) unpublished observations.
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© 2002 Humana Press Inc., Totowa, NJ
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Adelman, D.M., Simon, M.C. (2002). Hypoxic Gene Regulation in Differentiating ES Cells. In: Turksen, K. (eds) Embryonic Stem Cells. Methods in Molecular Biology™, vol 185. Springer, Totowa, NJ. https://doi.org/10.1385/1-59259-241-4:55
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DOI: https://doi.org/10.1385/1-59259-241-4:55
Publisher Name: Springer, Totowa, NJ
Print ISBN: 978-0-89603-881-3
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