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Science 12 September 1997:
Vol. 277. no. 5332, pp. 1669 - 1672
DOI: 10.1126/science.277.5332.1669
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Reports

Regulation of Human Placental Development by Oxygen Tension

Olga Genbacev, Yan Zhou, John W. Ludlow, Susan J. Fisher *

Cytotrophoblasts, specialized placental cells, proliferate early in pregnancy and then differentiate into tumor-like cells that establish blood flow to the placenta by invading the uterus and its vasculature. In this study, cytotrophoblasts cultured under hypoxic conditions (2 percent oxygen), mimicking the environment near the uterine surface before 10 weeks of gestation, continued proliferating and differentiated poorly. When cultured in 20 percent oxygen, mimicking the environment near uterine arterioles, the cells stopped proliferating and differentiated normally. Thus, oxygen tension determines whether cytotrophoblasts proliferate or invade, thereby regulating placental growth and cellular architecture.

O. Genbacev and Y. Zhou, Department of Stomatology, University of California, San Francisco, CA 94143-0512, USA.
J. W. Ludlow, Department of Biochemistry and Biophysics, University of Rochester, Cancer Center, Rochester, NY 14642, USA.
S. J. Fisher, Departments of Stomatology; Obstetrics, Gynecology and Reproductive Sciences; Pharmaceutical Chemistry; and Anatomy, University of California, San Francisco, CA 94143-0512, USA.
*   To whom correspondence should be addressed at HSW 604, Box 0512, University of California, San Francisco, CA 94143-0512, USA. E-mail: sfisher{at}cgl.ucsf.edu

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Posttranscriptional Regulation of Human Leukocyte Antigen G During Human Extravillous Cytotrophoblast Differentiation.
J. Copeman, R. N.N. Han, I. Caniggia, M. McMaster, S. J. Fisher, and J. C. Cross (2000)
Biol Reprod 62, 1543-1550
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Expression of Matrix Metalloproteinase-2, -9, and -14, Tissue Inhibitors of Metalloproteinase-1, and Matrix Proteins in Human Placenta During the First Trimester.
P. Xu, Y.-l. Wang, S.-j. Zhu, S.-y. Luo, Y.-s. Piao, and L.-z. Zhuang (2000)
Biol Reprod 62, 988-994
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Extracellular Matrix Composition and Hypoxia Regulate the Expression of HLA-G and Integrins in a Human Trophoblast Cell Line.
B. A. Kilburn, J. Wang, Z. M. Duniec-Dmuchkowski, R. E. Leach, R. Romero, and D. R. Armant (2000)
Biol Reprod 62, 739-747
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Id-2 regulates critical aspects of human cytotrophoblast differentiation, invasion and migration.
M. Janatpour, M. McMaster, O Genbacev, Y Zhou, J Dong, J. Cross, M. Israel, and S. Fisher (2000)
Development 127, 549-558
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Multilineage embryonic hematopoiesis requires hypoxic ARNT activity.
D. M. Adelman, E. Maltepe, and M. C. Simon (1999)
Genes & Dev. 13, 2478-2483
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Multiple Roles for Heparin-Binding Epidermal Growth Factor-Like Growth Factor Are Suggested by Its Cell-Specific Expression during the Human Endometrial Cycle and Early Placentation.
R. E. Leach, R. Khalifa, N. D. Ramirez, S. K. Das, J. Wang, S. K. Dey, R. Romero, and D. R. Armant (1999)
J. Clin. Endocrinol. Metab. 84, 3355-3363
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Preeclampsia Is Associated with Widespread Apoptosis of Placental Cytotrophoblasts within the Uterine Wall.
E. DiFederico, O. Genbacev, and S. J. Fisher (1999)
Am. J. Pathol. 155, 293-301
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Mouse ATF-2 Null Mutants Display Features of a Severe Type of Meconium Aspiration Syndrome.
T. Maekawa, F. Bernier, M. Sato, S. Nomura, M. Singh, Y. Inoue, T. Tokunaga, H. Imai, M. Yokoyama, A. Reimold, et al. (1999)
J. Biol. Chem. 274, 17813-17819
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Development of Cytotrophoblast Columns from Explanted First-Trimester Human Placental Villi: Role of Fibronectin and Integrin {alpha}5ß1.
J. D. Aplin, T. Haigh, C. J.P. Jones, H. J. Church, and L. Vicovac (1999)
Biol Reprod 60, 828-838
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Oxygen tension modulates ß-globin switching in embryoid bodies.
S. BICHET, R. H. WENGER, G. CAMENISCH, A. ROLFS, W. EHLEBEN, T. PORWOL, H. ACKER, J. FANDREY, C. BAUER, and M. GASSMANN (1999)
FASEB J 13, 285-295
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