The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Oxygen-Regulated Gene Expression in Bovine Blastocysts1
Abstract
Oxygen concentrations used during in vitro embryo culture can influence embryo development, cell numbers, and gene expression. Here we propose that the preimplantation bovine embryo possesses a molecular mechanism for the detection of, and response to, oxygen, mediated by a family of basic helix-loop-helix transcription factors, the hypoxia-inducible factors (HIFs). Day 5 compacting bovine embryos were cultured under different oxygen tensions (2%, 7%, 20%) and the effect on the expression of oxygen-regulated genes, development, and cell number allocation and HIFalpha protein localization were examined. Bovine in vitro-produced embryos responded to variations in oxygen concentration by altering gene expression. GLUT1 expression was higher following 2% oxygen culture compared with 7% and 20% cultured blastocysts. HIF mRNA expression (HIF1alpha, HIF2alpha) was unaltered by oxygen concentration. HIF2alpha protein was predominantly localized to the nucleus of blastocysts. In contrast, HIF1alpha protein was undetectable at any oxygen concentration or in the presence of the HIF protein stabilizer desferrioxamine (DFO), despite being detectable in cumulus cells following normal maturation conditions, acute anoxic culture, or in the presence of DFO. Oxygen concentration also significantly altered inner cell mass cell proportions at the blastocyst stage. These results suggest that oxygen can influence gene expression in the bovine embryo during postcompaction development and that these effects may be mediated by HIF2alpha.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Animal studies have confirmed that HIFs are expressed at the blastocyst stage of development (243), and that they are essential for normal placental development.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [243]
Citations
Cites
Wang, G. L., Jiang, B. H., Rue, E. A., & Semenza, G. L. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5510 · Cited by 6,212
Heterozygous embryonic lethality induced by targeted inactivation of the VEGF gene
Ferrara, N., Carver-Moore, K., Chen, H., Dowd, M., Lu, L., O’Shea, K. S., Powell-Braxton, L., Hillan, K. J., & Moore, M. W. (1996) · Nature · doi:10.1038/380439a0 · Cited by 3,661
A conserved family of prolyl-4-hydroxylases that modify HIF
Bruick, R. K., & McKnight, S. L. (2001) · Science · doi:10.1126/science.1066373 · Cited by 2,549
Cellular and developmental control of O 2 homeostasis by hypoxia-inducible factor 1α
Iyer, N. V., Kotch, L. E., Agani, F., Leung, S. W., Laughner, E., Wenger, R. H., Gassmann, M., Gearhart, J. D., Lawler, A. M., Yu, A. Y., et al. (1998) · Genes & Development · doi:10.1101/gad.12.2.149 · Cited by 2,476
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892
Molecular and Biological Properties of the Vascular Endothelial Growth Factor Family of Proteins
Ferrara, N., Houck, K. A., Jakeman, L. B., & LEUNG, D. W. (1992) · Endocrine Reviews · doi:10.1210/edrv-13-1-18 · Cited by 1,655
HIF‐1α is required for solid tumor formation and embryonic vascularization
Ryan, H. E., Lo, J., & Johnson, R. S. (1998) · The EMBO Journal · doi:10.1093/emboj/17.11.3005 · Cited by 1,579
Asparagine Hydroxylation of the HIF Transactivation Domain: A Hypoxic Switch
Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J., & Whitelaw, M. L. (2002) · Science · doi:10.1126/science.1068592 · Cited by 1,558
Guerin, P. J. (2001) · Human Reproduction Update · doi:10.1093/humupd/7.2.175 · Cited by 1,419
HIF-1 and mechanisms of hypoxia sensing
Semenza, G. L. (2001) · Current Opinion in Cell Biology · doi:10.1016/s0955-0674(00)00194-0 · Cited by 1,301
Research works printed but not linked: 2
- 2003, Proceedings of the 34th annual conference of the Society for Reproductive Biology
- 2003, Proceedings of the 2nd world congress on fetal origins of adult disease
Cited by
Sorted by citations
The role of oxygen availability in embryonic development and stem cell function
Simon, M. C., & Keith, B. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2354 · Cited by 1,015
Covello, K. L., Kehler, J., Yu, H., Gordan, J. D., Arsham, A. M., Hu, C., Labosky, P. A., Simon, M. C., & Keith, B. (2006) · Genes & Development · doi:10.1101/gad.1399906 · Cited by 850
Low O 2 tensions and the prevention of differentiation of hES cells
Ezashi, T., Das, P., & Roberts, R. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0501283102 · Cited by 824
Placental Origins of Chronic Disease
Burton, G. J., Fowden, A. L., & Thornburg, K. L. (2016) · Physiological Reviews · doi:10.1152/physrev.00029.2015 · Cited by 717
Mitochondrial Regulation of Cell Cycle and Proliferation
Arciuch, V. G. A., Elguero, M. E., Poderoso, J. J., & Carreras, M. C. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4085 · Cited by 449
Metadata
- Authors
- Harvey, A. J., Kind, K. L., Pantaleon, M., Armstrong, D. T., & Thompson, J. G.
- Affiliations
- Queen Elizabeth Hospital (AU)
- The University of Queensland (AU)
- Corresponding author
- Harvey, A.J.
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-10-01
- Volume
- 71
- Issue
- 4
- Pages
- 1108-1119
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2154875545
- Cited by
- 189
- References
- 66
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 2 · 2022: 14 · 2021: 6 · 2020: 15 · 2019: 4 · 2018: 4 · 2017: 10 · 2016: 6 · 2015: 13 · 2014: 4 · 2013: 13 · 2012: 9
- FWCI
- 12.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Funders
- Medical Research Council
- National Health and Medical Research Council (157941)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Reproductive Physiology in Livestock
- Keywords
- oxygen regulation, bovine blastocyst, hypoxia-inducible factor, HIF-1α, HIF-2α, GLUT1, embryo culture, oxygen partial pressure, deferoxamine, inner cell mass, bHLH transcription factors, embryonic development, cumulus cells
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Animals, Blastocyst, Cattle, Monosaccharide Transport Proteins, Oxygen, RNA, Messenger, Tissue Distribution, Transcription Factors, Gene Expression Regulation, Developmental, Vascular Endothelial Growth Factor A, Embryo Culture Techniques, Embryonic Development, Glucose Transporter Type 1, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review