Regulation of Hypoxia Inducible Factors (HIF) in Hypoxia and Normoxia During Placental Development

Patel, J.; Landers, K.; Mortimer, R.H.; Richard, K.

doi:10.1016/j.placenta.2010.08.008

Cited by 157Pregnancy and preeclampsia studiesReproductive System and PregnancyCancer, Hypoxia, and Metabolism

Regulation of Hypoxia Inducible Factors (HIF) in Hypoxia and Normoxia During Placental Development

Patel, J., Landers, K., Mortimer, R.H., Richard, K.·2010·Placenta

DOI 10.1016/j.placenta.2010.08.008

Open this paper in CoChat — free account

Abstract

During the first trimester of pregnancy the human placenta develops in an hypoxic environment caused by the occlusion of uterine spiral arterioles by extravillous trophoblasts (EVT). This period of low oxygen tension is crucial for successful pregnancy. In low oxygen environments, Hypoxia Inducible Factors (HIF) are the main regulators in the transcription of a number of genes. Target genes can induce anaerobic processes, reducing oxygen consumption, or promote angiogenesis, which establishes and enhances the vascular environment. The HIFs can function throughout all stages of placental differentiation and growth both in normal and pathological pregnancies (compromised by hypoxia/ischemia). Interestingly, HIFs respond to a multitude of changes during pregnancy, including 1) low oxygen, 2) renin-angiotensin system (RAS), 3) cytokines, and 4) growth factors, all of which regulate placental function. This review explores oxygen-dependent and oxygen-independent regulation and the role of HIF in placental development and differentiation.

Integrity signals

Registry

Crossref · 10.1016/j.placenta.2010.08.008

Cites

77 of 77 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

HIFs can be stabilized by factors other than hypoxia, including reactive oxygen and nitrogen species, angiotensin, growth factors and cytokines.
“Interpretation of these data is difficult given that it is now realized that HIFs can be stabilized by factors other than hypoxia, including reactive oxygen and nitrogen species, angiotensin, growth factors and cytokines (433, 444), many of which are changing during early pregnancy.”
From Placental Origins of Chronic Disease (2016) · cites this paper as [433]

Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O <sub>2</sub> -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
HIFα Targeted for VHL-Mediated Destruction by Proline Hydroxylation: Implications for O <sub>2</sub> Sensing
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · see citing works
Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia
Maynard, S. E., Min, J.-Y., Merchan, J., Lim, K.-H., Li, J., Mondal, S., Libermann, T. A., Morgan, J. P., Sellke, F. W., Stillman, I. E., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci17189 · Cited by 4,101 · see citing works
Inhibition of vascular endothelial cell growth factor activity by an endogenously encoded soluble receptor.
Kendall, R. L., & Thomas, K. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10705 · Cited by 1,393 · see citing works
Natural killer cells and pregnancy
Moffett-King, A. (2002) · Nature Reviews Immunology · doi:10.1038/nri886 · Cited by 1,235 · see citing works
Hypoxia-inducible factor (HIF-1)α: its protein stability and biological functions
Lee, J., Bae, S.-H., Jeong, J., Kim, S., & Kim, K. (2004) · Experimental & Molecular Medicine · doi:10.1038/emm.2004.1 · Cited by 1,119 · see citing works
Onset of Maternal Arterial Blood Flow and Placental Oxidative Stress
Jauniaux, E., Watson, A. L., Hempstock, J., Bao, Y.-P., Skepper, J. N., & Burton, G. J. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64849-3 · Cited by 1,057 · see citing works
Regulation of Human Placental Development by Oxygen Tension
Genbačev, O., Zhou, Y., Ludlow, J. W., & Fisher, S. J. (1997) · Science · doi:10.1126/science.277.5332.1669 · Cited by 914 · see citing works
The role of the spiral arteries in the pathogenesis of pre-eclampsia.
Brosens, I. A., Robertson, W. B., & Dixon, H. G. (1970) · PubMed · Cited by 894 · see citing works
Molecular basis of the VHL hereditary cancer syndrome
Kaelin, W. G. (2002) · Nature Reviews Cancer · doi:10.1038/nrc885 · Cited by 865 · see citing works
Patients with preeclampsia develop agonistic autoantibodies against the angiotensin AT1 receptor
Wallukat, G., Homuth, V., Fischer, T., Lindschau, C., Horstkamp, B., Jüpner, A., Baur, E., Nissen, E., Vetter, K. J., Neichel, D., et al. (1999) · Journal of Clinical Investigation · doi:10.1172/jci4106 · Cited by 825 · see citing works
Oxygen measurements in endometrial and trophoblastic tissues during early pregnancy.
Rodesch, F., Simon, P., Donner, C., & Jauniaux, E. R. M. (1992) · PubMed · Cited by 753 · see citing works
IL‐1β mediated up‐regulation of HIF‐lα via an NFkB/COX‐2 pathway identifies HIF‐1 as a critical link between inflammation and oncogenesis
Jung, Y., Isaacs, J. S., Lee, S., Trepel, J. B., & Neckers, L. (2003) · The FASEB Journal · doi:10.1096/fj.03-0329fje · Cited by 681 · see citing works
Placental bed spiral arteries in the hypertensive disorders of pregnancy
Pijnenborg, R., Anthony, J., Davey, D. A., Rees, A., Tiltman, A. J., Vercruysse, L., & Assche, A. V. (1991) · BJOG An International Journal of Obstetrics & Gynaecology · doi:10.1111/j.1471-0528.1991.tb13450.x · Cited by 667 · see citing works
The Role of Hypoxia in Development of the Mammalian Embryo
Dunwoodie, S. L. (2009) · Developmental Cell · doi:10.1016/j.devcel.2009.11.008 · Cited by 651 · see citing works
Hypoxia-inducible factor-1 mediates the biological effects of oxygen on human trophoblast differentiation through TGFβ3
Caniggia, I., Mostachfi, H., Winter, J., Gassmann, M., Lye, S. J., Kuliszewski, M., & Post, M. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8316 · Cited by 644 · see citing works
Reciprocal positive regulation of hypoxia-inducible factor 1alpha and insulin-like growth factor 2.
Feldser, D. M., Agani, F. H., Iyer, N. V., Pak, B. J., Ferreira, G., & Semenza, G. L. (1999) · PubMed · Cited by 638 · see citing works
Placental Stress and Pre-eclampsia: A Revised View
Redman, C. W. G., & Sargent, I. L. (2009) · Placenta · doi:10.1016/j.placenta.2008.11.021 · Cited by 601 · see citing works
Insulin induces transcription of target genes through the hypoxia‐inducible factor HIF‐1α/ARNT
Zelzer, E., Levy, Y., Kahana, C., Shilo, B., Rubinstein, M., & Cohen, B. (1998) · The EMBO Journal · doi:10.1093/emboj/17.17.5085 · Cited by 575 · see citing works
Hormonal Control of Ovoimplantation
Psychoyos, A. (1974) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60999-1 · Cited by 481 · see citing works
Maternal Uterine Vascular Remodeling During Pregnancy
Osol, G., & Mandalà, M. (2009) · Physiology · doi:10.1152/physiol.00033.2008 · Cited by 479 · see citing works
Interleukin-1β and Tumor Necrosis Factor- Stimulate DNA Binding of Hypoxia-Inducible Factor-1
Hellwig‐Bürgel, T., Rutkowski, K., Metzen, E., Fandrey, J., & JELKMANN, W. E. B. (1999) · Blood · doi:10.1182/blood.v94.5.1561.417a06_1561_1567 · Cited by 475 · see citing works
Angiogenesis and vasculogenesis in pregnancy
Zygmunt, M., Herr, F., Münstedt, K., Lang, U., & Liang, O. D. (2003) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/s0301-2115(03)00168-4 · Cited by 473 · see citing works
Overexpression of the Soluble Vascular Endothelial Growth Factor Receptor in Preeclamptic Patients: Pathophysiological Consequences
Tsatsaris, V., Goffin, F., Munaut, C., Brichant, J.-F., Pignon, M.-R., Noël, A., Schaaps, J., CABROL, D., Frankenne, F., & Foidart, J. (2003) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-030528 · Cited by 461 · see citing works
Maternal arterial connections to the placental intervillous space during the first trimester of human pregnancy: The Boyd Collection revisited
Burton, G. J., Jauniaux, E. R. M., & Watson, A. L. (1999) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(99)70518-1 · Cited by 453 · see citing works
Catalytic properties of the asparaginyl hydroxylase (FIH) in the oxygen sensing pathway are distinct from those of its prolyl 4-hydroxylases
Koivunen, P., Hirsilä, M., Günzler, V., Kivirikko, K. I., & Myllyharju, J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312254200 · Cited by 447 · see citing works
Induction of HIF–1α in response to hypoxia is instantaneous
Jewell, U. R., Kvietikova, I., Scheid, A., Bauer, C., Wenger, R. H., & Gassmann, M. (2001) · The FASEB Journal · doi:10.1096/fj.00-0732fje · Cited by 443 · see citing works
Thrombin Activates the Hypoxia-Inducible Factor-1 Signaling Pathway in Vascular Smooth Muscle Cells
Görlach, A., Diebold, I., Schini‐Kerth, V. B., Berchner‐Pfannschmidt, U., Roth, U., Brandes, R. P., Kietzmann, T., & Busse, R. (2001) · Circulation Research · doi:10.1161/hh1301.092678 · Cited by 416 · see citing works
Oxygen and Placental Development During the First Trimester: Implications for the Pathophysiology of Pre-eclampsia
Caniggia, I., Winter, J., Lye, S. J., & Post, M. (2000) · Placenta · doi:10.1053/plac.1999.0522 · Cited by 377 · see citing works
Mechanism of control of trophoblast invasion in situ
Graham, C. H., & Lala, P. K. (1991) · Journal of Cellular Physiology · doi:10.1002/jcp.1041480207 · Cited by 371 · see citing works
Inhibition of TGF-β3 restores the invasive capability of extravillous trophoblasts in preeclamptic pregnancies
Caniggia, I., Grisaru-Gravnosky, S., Kuliszewski, M. J., Post, M., & Lye, S. J. (1999) · Journal of Clinical Investigation · doi:10.1172/jci6380 · Cited by 360 · see citing works
The anatomy of the normal placenta
Huppertz, B. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2008.055277 · Cited by 352 · see citing works
The expression of insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) genes in the human placenta and membranes: evidence for IGF-IGFBP interactions at the feto-maternal interface
Han, V. K. M., Bassett, N. S., Walton, J., & Challis, J. R. G. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.7.8675597 · Cited by 341 · see citing works
Transforming Growth Factor β1 Induces Hypoxia-inducible Factor-1 Stabilization through Selective Inhibition of PHD2 Expression
McMahon, S., Charbonneau, M., Grandmont, S., Richard, D. E., & Dubois, C. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m604507200 · Cited by 329 · see citing works
The Functional Role of the Renin–Angiotensin System in Pregnancy and Preeclampsia
Irani, R. A., & Xia, Y. (2008) · Placenta · doi:10.1016/j.placenta.2008.06.011 · Cited by 293 · see citing works
Oxygen, the Janus gas; its effects on human placental development and function
Burton, G. J. (2008) · Journal of Anatomy · doi:10.1111/j.1469-7580.2008.00978.x · Cited by 281 · see citing works
Tumor Necrosis Factor-α Inhibits Trophoblast Migration through Elevation of Plasminogen Activator Inhibitor-1 in First-Trimester Villous Explant Cultures
Bauer, S., Pollheimer, J., Hartmann, J., Husslein, P. W., Aplin, J., & Knöfler, M. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031351 · Cited by 270 · see citing works
Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Pringle, K. G., Kind, K. L., Sferruzzi-Perri, A. N., Thompson, J. G., & Roberts, C. T. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmp046 · Cited by 259 · see citing works
Human cytotrophoblast invasion is up-regulated by epidermal growth factor: Evidence that paracrine factors modify this process
Bass, K. E., Morrish, D. W., Roth, I., Bhardwaj, D., Taylor, R. N., Zhou, Y., & Fisher, S. J. (1994) · Developmental Biology · doi:10.1006/dbio.1994.1223 · Cited by 242 · see citing works
Plasminogen Activator Inhibitor-1 Represses Integrin- and Vitronectin-Mediated Cell Migration Independently of Its Function as an Inhibitor of Plasminogen Activation
Kjøller, L., Kanse, S. M., Kirkegaard, T., Rodenburg, K. W., Rønne, E., Goodman, S. L., Preissner, K. T., Ossowski, L., & Andreasen, P. A. (1997) · Experimental Cell Research · doi:10.1006/excr.1997.3540 · Cited by 233 · see citing works
The Human First Trimester Gestational Sac Limits Rather than Facilitates Oxygen Transfer to the Foetus—A Review
Jauniaux, E. R. M., Gulbis, B., & Burton, G. J. (2003) · Placenta · doi:10.1053/plac.2002.0932 · Cited by 231 · see citing works
Hypoxia-inducible factor asparaginyl hydroxylase (FIH-1) catalyses hydroxylation at the β-carbon of asparagine-803
McNEILL, L. A., HEWITSON, K. S., CLARIDGE, T. D., SEIBEL, J. F., HORSFALL, L. E., & SCHOFIELD, C. J. (2002) · Biochemical Journal · doi:10.1042/bj20021162 · Cited by 215 · see citing works
Structural basis for negative regulation of hypoxia-inducible factor-1α by CITED2
Freedman, S. J., Sun, Z.-Y. J., Kung, A. L., France, D. S., Wagner, G., & Eck, M. J. (2003) · Nature Structural & Molecular Biology · doi:10.1038/nsb936 · Cited by 200 · see citing works
Insulin-like growth factor I and II regulate the life cycle of trophoblast in the developing human placenta
Forbes, K. A., Westwood, M., Baker, P. N., & Aplin, J. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00035.2008 · Cited by 187 · see citing works
Uterine Spiral Artery Remodeling Involves Endothelial Apoptosis Induced by Extravillous Trophoblasts Through Fas/FasL Interactions
Ashton, S. V., Whitley, G. S. J., Dash, P. R., Wareing, M., Crocker, I. P., Baker, P. N., & Cartwright, J. E. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000148547.70187.89 · Cited by 185 · see citing works
The Role of NF‐κB in Hypoxia‐Induced Gene Expression
Taylor, C. T., & Cummins, E. P. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.05024.x · Cited by 175 · see citing works
Hypoxia and angiogenesis: regulation of hypoxia-inducible factors via novel binding factors
Chen, L., Endler, A., & Shibasaki, F. (2009) · Experimental & Molecular Medicine · doi:10.3858/emm.2009.41.12.103 · Cited by 164 · see citing works
The IGF Axis and Placental Function
Forbes, K. A., & Westwood, M. (2008) · Hormone Research in Paediatrics · doi:10.1159/000112585 · Cited by 164 · see citing works
Quantitative description of the elaboration and maturation of villi from 10 weeks of gestation to term
Jackson, M., Mayhew, T. M., & Boyd, P. A. (1992) · Placenta · doi:10.1016/0143-4004(92)90060-7 · Cited by 158 · see citing works
The phosphorylation pattern of insulin-like growth factor-binding protein-1 in normal plasma is different from that in amniotic fluid and changes during pregnancy
Westwood, M., Gibson, M., Davies, A. J., Young, R. J., & White, A. E. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.79.6.7527409 · Cited by 156 · see citing works
Vascular biology in implantation and placentation
Huppertz, B., & Peeters, L. L. H. (2005) · Angiogenesis · doi:10.1007/s10456-005-9007-8 · Cited by 155 · see citing works
Invasive Trophoblasts Stimulate Vascular Smooth Muscle Cell Apoptosis by a Fas Ligand-Dependent Mechanism
Harris, L. K., Keogh, R. J., Wareing, M., Baker, P. N., Cartwright, J. E., Aplin, J. D., & Whitley, G. S. J. (2006) · The American Journal of Pathology · doi:10.2353/ajpath.2006.060265 · Cited by 147 · see citing works
Gabor Than Award Lecture 2008: Pre-eclampsia – From Placental Oxidative Stress to Maternal Endothelial Dysfunction
Cindrová‐Davies, T. (2009) · Placenta · doi:10.1016/j.placenta.2008.11.020 · Cited by 145 · see citing works
Localization of transforming growth factor β and its natural inhibitor decorin in the human placenta and decidua throughout gestation
Lysiak, J. J., Hunt, J. A., Pringle, G. A., & Lala, P. K. (1995) · Placenta · doi:10.1016/0143-4004(95)90110-8 · Cited by 136 · see citing works
Regulation of extravillous trophoblast invasion by uterine natural killer cells is dependent on gestational age
Lash, G. E., Otun, H., Innes, B. A., Percival, K., Searle, R. F., Robson, S. C., & Bulmer, J. N. (2010) · Human Reproduction · doi:10.1093/humrep/deq050 · Cited by 135 · see citing works
Dynamic HIF1A Regulation During Human Placental Development1
Ietta, F., Wu, Y., Winter, J., Xu, J., Wang, J., Post, M., & Caniggia, I. (2006) · Biology of Reproduction · doi:10.1095/biolreprod.106.051557 · Cited by 127 · see citing works
Local regulation of implantation at the human fetal-maternal interface
Dimitriadis, E., Nie, G., Hannan, N. J., Paiva, P., & Salamonsen, L. A. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082772ed · Cited by 125 · see citing works
Regulation of Trophoblast Invasion by IL‐1β and TGF‐ β1
Karmakar, S., & Das, C. R. (2002) · American Journal of Reproductive Immunology · doi:10.1034/j.1600-0897.2002.01151.x · Cited by 123 · see citing works
Changes in Active and Inactive Renin throughout Pregnancy*
Hsueh, W. A., Luetscher, J. A., Carlson, E. J., GRISLIS, G., Fraze, E., & McHargue, A. M. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-54-5-1010 · Cited by 123 · see citing works
Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta
Withington, S. L., Scott, A., Saunders, D. N., Floro, K. L., Preis, J. I., Michalicek, J., Maclean, K., Sparrow, D. B., Martı́nez-Barberá, J. P., & Dunwoodie, S. L. (2006) · Developmental Biology · doi:10.1016/j.ydbio.2006.02.025 · Cited by 112 · see citing works
Human Spiral Artery Renin-Angiotensin System
Morgan, T. K., Craven, C., & Ward, K. (1998) · Hypertension · doi:10.1161/01.hyp.32.4.683 · Cited by 108 · see citing works
Microtubule Disruption Utilizes an NFκB-dependent Pathway to Stabilize HIF-1α Protein
Jung, Y., Isaacs, J. S., Lee, S., Trepel, J. B., & Neckers, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209804200 · Cited by 99 · see citing works
Sodium excretion in normal and hypertensive pregnancy: A prospective study
Brown, M. A., Gallery, E. D. M., Ross, M. R., & Esber, R. P. (1988) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(88)80071-1 · Cited by 85 · see citing works
Review: LIF and IL11 in trophoblast-endometrial interactions during the establishment of pregnancy
Dimitriadis, E., Menkhorst, E. M., Salamonsen, L. A., & Paiva, P. (2010) · Placenta · doi:10.1016/j.placenta.2009.12.027 · Cited by 85 · see citing works
Placental ischemia and soluble fms-like tyrosine kinase 1: Cause or consequence of preeclampsia?
Karumanchi, S. A., & Epstein, F. H. (2007) · Kidney International · doi:10.1038/sj.ki.5002281 · Cited by 85 · see citing works
NO and TNF-α released from activated macrophages stabilize HIF-1α in resting tubular LLC-PK1 cells
Zhou, J., Fandrey, J., Schümann, J., Tiegs, G., & Brüne, B. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00294.2002 · Cited by 81 · see citing works
TNFα-Mediated Induction of PAI-1 Restricts Invasion of HTR-8/SVneo Trophoblast Cells
Huber, A. V., Saleh, L., Bauer, S., Husslein, P. W., & Knöfler, M. (2005) · Placenta · doi:10.1016/j.placenta.2005.02.012 · Cited by 73 · see citing works
Targeting the molecular basis for tumour hypoxia
Carroll, V. A., & Ashcroft, M. A. (2005) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399405009117 · Cited by 67 · see citing works
Insulin-Like Growth Factor-II Regulates the Expression of Vascular Endothelial Growth Factor by the Human Keratinocyte Cell Line HaCaT
Kwon, Y., Kwon, K., Moon, H.-E., Park, J. A., Choi, K.-S., Kim, Y. S., Jang, H., Oh, C., Lee, Y. M., Kwon, Y., et al. (2004) · Journal of Investigative Dermatology · doi:10.1111/j.0022-202x.2004.22735.x · Cited by 60 · see citing works
Evolution of Factors Affecting Placental Oxygen Transfer
Carter, A. M. (2008) · Placenta · doi:10.1016/j.placenta.2008.11.006 · Cited by 60 · see citing works
Attachment and differentiation in vitro of trophoblast from normal and preeclamptic human placentas
Pijnenborg, R., Luyten, C., Vercruysse, L., & Assche, F. A. V. (1996) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(96)70246-6 · Cited by 59 · see citing works
Normoxic Induction of the Hypoxic-Inducible Factor-1α by Interleukin-1β Involves the Extracellular Signal-Regulated Kinase 1/2 Pathway in Normal Human Cytotrophoblast Cells1
Dong, Q., Lin, H., Wang, H., Zhang, X., Liu, D., Li, Q., & Zhu, C. (2004) · Biology of Reproduction · doi:10.1095/biolreprod.103.025031 · Cited by 55 · see citing works
Transforming Growth Factor-β (TGFβ) Receptors I/II Differentially Regulate TGFβ1 and IGF-Binding Protein-3 Mitogenic Effects in the Human Placenta
Forbes, K. A., Souquet, B., Garside, R., Aplin, J., & Westwood, M. (2010) · Endocrinology · doi:10.1210/en.2009-0896 · Cited by 52 · see citing works
The Urokinase Plasminogen Activator (uPA) System in Uterine Natural Killer Cells in the Placental Bed During Early Pregnancy
Naruse, K., Lash, G. E., Bulmer, J. N., Innes, B. A., Otun, H. A., Searle, R. F., & Robson, S. C. (2009) · Placenta · doi:10.1016/j.placenta.2009.02.002 · Cited by 47 · see citing works
Complex Interactions Between Hypoxia Inducible Factors, Insulin-Like Growth Factor-II and Oxygen in Early Murine Trophoblasts
Pringle, K. G., Kind, K. L., Thompson, J. G., & Roberts, C. T. (2007) · Placenta · doi:10.1016/j.placenta.2007.05.009 · Cited by 38 · see citing works
Angiotensin II mimics the hypoxic effect on regulating trophoblast proliferation and differentiation in human placental explant cultures
荒木, 雅., Nomura, S., Ino, K., Sumigama, S., Yamamoto, E., Kotani, T., Hayakawa, H., Kajiyama, H., Shibata, K., Itakura, A., et al. (2007) · Life Sciences · doi:10.1016/j.lfs.2007.10.017 · Cited by 36 · see citing works
Opposite Effects of Transforming Growth Factor-β Activation and Rho-Associated Kinase Inhibition on Human Trophoblast Migration in a Reconstituted Placental-Endometrial Coculture System
Fafet, P., Rebouissou, C., Maudelondé, T., & Vignais, M. (2008) · Endocrinology · doi:10.1210/en.2008-0253 · Cited by 24 · see citing works

Flagged first, then by citations

3 of the 80 references couldn’t be matched to a known paper.

Sorted by citations

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 · see citing works
Matrix Metalloproteinases in Normal Pregnancy and Preeclampsia
Chen, J., & Khalil, R. A. (2017) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2017.04.001 · Cited by 280 · see citing works
Angiogenesis and intramembranous osteogenesis
Percival, C. J., & Richtsmeier, J. T. (2013) · Developmental Dynamics · doi:10.1002/dvdy.23992 · Cited by 266 · see citing works
“…commonly upregulated in regions of hypoxia (Pugh and Ratcliffe, 2003), but also upregulated via oxygenindependent mechanisms (Chun et al., 2002; Patel et al., 2010), is a promoter of VEGF expression and is known to directly regulate osteoblasts in endochondral bones (Towler, 2008; Rankin et…”
Background
MIR-210 modulates mitochondrial respiration in placenta with preeclampsia
Muralimanoharan, S., Maloyan, A., Mele, J., Guo, C., Myatt, L. G., & Myatt, L. (2012) · Placenta · doi:10.1016/j.placenta.2012.07.002 · Cited by 237 · see citing works
“In addition to hypoxia, inflammatory cytokines, estrogen and reactive oxygen species (ROS) are involved in the stabilization of HIF-1α during normoxia in a number of tissue types including placenta (9).”
Background
Thyroid hormones and fetal neurological development
Patel, J., Landers, K., Li, H., Mortimer, R. H., & Richard, K. (2011) · Journal of Endocrinology · doi:10.1530/joe-10-0444 · Cited by 232 · see citing works
“The T4-binding protein, transthyretin, produced in significant amounts by the choroid plexus, has been implicated in this transport, and transthyretin may be involved in delivery of CSF thyroid hormone to the brain (Patel et al. 2010).”
BackgroundSelf-citation
Trophoblast lineage specification, differentiation and their regulation by oxygen tension
Chang, C.-W., Wakeland, A. K., & Parast, M. M. (2017) · Journal of Endocrinology · doi:10.1530/joe-17-0402 · Cited by 176 · see citing works
Hypoxia Directs Human Extravillous Trophoblast Differentiation in a Hypoxia-Inducible Factor–Dependent Manner
Wakeland, A. K., Soncin, F., Moretto-Zita, M., Chang, C., Horii, M., Pizzo, D. P., Nelson, K. K., Laurent, L. C., & Parast, M. M. (2017) · American Journal Of Pathology · doi:10.1016/j.ajpath.2016.11.018 · Cited by 139 · see citing works
“13 The HIF complex is critical for embryonic development in mice, where loss of either HIF1 b /ARNT or both of the main a subunits (HIF1 a /HIF2 a ) leads to embryonic lethality at mid-gestation.”
Sex Steroids Modulate Uterine-Placental Vasculature: Implications for Obstetrics and Neonatal Outcomes
Maliqueo, M. A., Echiburú, B., & Crisosto, N. (2016) · Frontiers in Physiology · doi:10.3389/fphys.2016.00152 · Cited by 114 · see citing works
“Interestingly, recent evidence suggests that HIF-1α is also activated by non-hypoxic stimuli, such as growth factors, immunogenic cytokines, and sex steroids (Patel et al., 2010).”
Background
Lactic Acid: A Novel Signaling Molecule in Early Pregnancy?
Ma, L., Huang, X., Muyayalo, K. P., Mor, G., & Liao, A. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.00279 · Cited by 107 · see citing works
“Like the tumor microenvironment, the maternal-fetal interface in the first trimester of pregnancy has similar hypoxic, acidic, and immune features in the microenvironment (34, 73).”
Background
Impact of Exercise Training on Preeclampsia
Genest, D. S., Falcao, S., Gutkowska, J., & Lavoie, J. L. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.194050 · Cited by 107 · see citing works
Heightened Pro-Inflammatory Effect of Preeclamptic Placental Microvesicles on Peripheral Blood Immune Cells in Humans1
Holder, B. S., Tower, C. L., Jones, C. J. P., Aplin, J., & Abrahams, V. M. (2011) · Biology of Reproduction · doi:10.1095/biolreprod.111.097014 · Cited by 100 · see citing works
“Microvesicles were generated at 6% oxygen, the estimated physiological level in normal placenta after 11 wk [33, 34].”
Decidual T Cells Exhibit a Highly Differentiated Phenotype and Demonstrate Potential Fetal Specificity and a Strong Transcriptional Response to IFN
Powell, R., Lissauer, D. M., Tamblyn, J. A., Beggs, A. D., Cox, P. M., Moss, P. A. H., & Kilby, M. D. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700114 · Cited by 99 · see citing works
“a key role in modulating placental cell function under low oxygen conditions (61).”
Background
Immune cell activation by trophoblast‐derived microvesicles is mediated by syncytin 1
Holder, B. S., Tower, C. L., Forbes, K. A., Mulla, M. J., Aplin, J., & Abrahams, V. M. (2012) · Immunology · doi:10.1111/j.1365-2567.2012.03568.x · Cited by 97 · see citing works
An integrated model of preeclampsia: a multifaceted syndrome of the maternal cardiovascular-placental-fetal array
Yagel, S., Cohen, S. M., & Goldman‐Wohl, D. (2021) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2020.10.023 · Cited by 97 · see citing works
Hypoxia inhibits invasion of extravillous trophoblast cells through reduction of matrix metalloproteinase (MMP)-2 activation in the early first trimester of human pregnancy
Onogi, A., Naruse, K., Sado, T., Tsunemi, T., Shigetomi, H., 野口, 武., Yamada, Y., Akasaki, M., Oi, H., & Kobayashi, H. (2011) · Placenta · doi:10.1016/j.placenta.2011.06.023 · Cited by 89 · see citing works
Small regulatory RNAs controlled by genomic imprinting and their contribution to human disease
Girardot, M., Cavaillé, J., & Feil, R. (2012) · Epigenetics · doi:10.4161/epi.22884 · Cited by 85 · see citing works
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation and promotes invasion
Highet, A. R., Khoda, S. M.-E., Buckberry, S., Leemaqz, S., Bianco‐Miotto, T., Harrington, E., Ricciardelli, C., & Roberts, C. T. (2015) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2015.10.004 · Cited by 69 · see citing works
Fetal ERAP2 variation is associated with preeclampsia in African Americans in a case-control study
Hill, L. D., Hilliard, D. D., York, T. P., Srinivas, S. K., Kusanovic, J. P., Gómez, R., Elovitz, M. A., Romero, R. J., & Strauss, J. F. (2011) · BMC Medical Genetics · doi:10.1186/1471-2350-12-64 · Cited by 68 · see citing works
“HIF-1a is regulated through oxygen dependent and independent mechanisms, and several of the cytokines that are modulated by ERAP2 have been shown to participate in the oxygen independent regulation mechanisms[ 70 ].”
Background
Effect of oxygen on multidrug resistance in the first trimester human placenta
Lye, P., Bloise, E., Dunk, C., Javam, M., Gibb, W., Lye, S. J., & Matthews, S. G. (2013) · Placenta · doi:10.1016/j.placenta.2013.05.010 · Cited by 62 · see citing works
“This process promotes dilation of the maternal spiral arterioles, 15 which increases blood flow into the intervillous space, providing nutrient and oxygen supply for the 16 growing placenta and developing embryo [5,6].”
Background
Fatty acid-induced angiogenesis in first trimester placental trophoblast cells: Possible roles of cellular fatty acid-binding proteins
Basak, S., Das, M. K., & Duttaroy, A. K. (2013) · Life Sciences · doi:10.1016/j.lfs.2013.09.024 · Cited by 62 · see citing works
“The angiogenic effect of hypoxia is mediated via VEGF, ANGPTL4 and eNOS,which are activated by HIF-α, a key transcription factor induced in hypoxia (Patel et al., 2010).”
Background
Effect of Preeclampsia on Placental Function: Influence of Sexual Dimorphism, microRNA’s and Mitochondria
Myatt, L., Muralimanoharan, S., & Maloyan, A. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-1031-1_12 · Cited by 62 · see citing works
“In addition to hypoxia, infl ammatory cytokines, estrogen and reactive oxygen species (ROS) stabilize HIF-1α during normoxia in a number of tissue types including placenta [ 50 ].”
Background
Vascular endothelial growth factor (VEGF) regulation by hypoxia inducible factor-1 alpha (HIF1A) starts and peaks during endometrial breakdown, not repair, in a mouse menstrual-like model
Chen, X., Liu, J., He, B., Li, Y., Liu, S., Wu, B., Wang, S., Zhang, S., Xu, X., & Wang, J. (2015) · Human Reproduction · doi:10.1093/humrep/dev156 · Cited by 61 · see citing works
“Hypoxia was shown to be a key factor in the process of placental development (Genbacev et al., 1997; Patel et al., 2010; Semenza, 2012).”
Background
Expansion of the fetoplacental vasculature in late gestation is strain dependent in mice
Rennie, M. Y., Detmar, J., Whiteley, K. J., Jurisicova, A., Adamson, S. L., & Sled, J. G. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00776.2011 · Cited by 57 · see citing works
Longitudinal intravital imaging of mouse placenta
Zhu, X., Huang, Q., Jiang, L., Nguyen, V. T., Vu, T., Devlin, G. W., Jabbar, S., Wang, X., Chen, Y., Ma, L., et al. (2024) · Science Advances · doi:10.1126/sciadv.adk1278 · Cited by 57 · see citing works
“The low-oxygen environment during early pregnancy helps placental development by promoting angiogenesis and protecting the developing placenta and fetus from oxidative stress ( 40 – 42 ).”
Background
Increased MMPs expression and decreased contraction in the rat myometrium during pregnancy and in response to prolonged stretch and sex hormones
Yin, Z., Sada, A., Reslan, O. M., Narula, N. G., & Khalil, R. A. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00553.2011 · Cited by 55 · see citing works
Regulation of drug transporter expression and function in the placenta
Štaud, F., & Čečková, M. (2015) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.2015.1005073 · Cited by 53 · see citing works
“In addition, several HIFs have been identified as crucial regulators of gene transcription in many tissues including the placenta [126].”
Background
Placental Regulation of Inflammation and Hypoxia after TNF ‐α Infusion in Mice
Bobek, G., Surmon, L., Colafella, K. M. M., Makris, A., & Hennessy, A. (2015) · American Journal of Reproductive Immunology · doi:10.1111/aji.12417 · Cited by 53 · see citing works
Transthyretin and the human placenta
Landers, K., Mortimer, R. H., & Richard, K. (2013) · Placenta · doi:10.1016/j.placenta.2013.04.013 · Cited by 51 · see citing works
“Interestingly, C/EBP andAP-1 are also up-regulated in hypoxic conditions and interact with hypoxia-inducible factor-1a (HIF-1a) [70].”
BackgroundSelf-citation
Architecture of Normal Villous Trees
Benirschke, K., Burton, G. J., & Baergen, R. N. (2012) · Springer eBooks · doi:10.1007/978-3-642-23941-0_7 · Cited by 50 · see citing works
Gestation Dependant Changes in Angiogenic Factors and Their Associations with Fetal Growth Measures in Normotensive Pregnancy
Sundrani, D. P., Khot, V., Pisal, H., Mehendale, S. S., Wagh, G. N., Joshi, A. A., & Joshi, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0054153 · Cited by 50 · see citing works
“It is known that during the first trimester of pregnancy the human placenta develops in a hypoxic environment which is essential for placental and embryonic development [20].”
Modeling preeclampsia using human induced pluripotent stem cells
Horii, M., Morey, R. E., Bui, T., Touma, O., Nelson, K. K., Cho, H. Y., Rishik, H., Laurent, L. C., & Parast, M. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-85230-5 · Cited by 47 · see citing works
The Hypoxic Placenta
Tissot van Patot, M. C., Ebensperger, G., Gassmann, M., & Llanos, A. J. (2012) · High Altitude Medicine & Biology · doi:10.1089/ham.2012.1046 · Cited by 45 · see citing works
“An increasing number of excellent reviews have focused on hypoxia-mediated placental responses (Charnock-Jones et al., 2004; Simon et al., 2008; Burton, 2009; Dunwoodie, 2009; Patel et al., 2010; Pringle et al., 2010; Burton et al., 2011; Tuuli et al., 2011).”
Placental development during early pregnancy in sheep: effects of embryo origin on vascularization
Grazul‐Bilska, A. T., Johnson, M. L., Borowicz, P. P., Bilski, J. J., Cymbaluk, T., Norberg, S., Redmer, D. A., & Reynolds, L. P. (2014) · Reproduction · doi:10.1530/rep-13-0663 · Cited by 45 · see citing works
Adrenomedullin and pregnancy: perspectives from animal models to humans
Lenhart, P., & Caron, K. M. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.02.007 · Cited by 45 · see citing works
Increased Apoptosis, Altered Oxygen Signaling, and Antioxidant Defenses in First-Trimester Pregnancies with High-Resistance Uterine Artery Blood Flow
Leslie, K., Whitley, G. S. J., Herse, F., Dechend, R., Ashton, S. V., Laing, K. G., Thilaganathan, B., & Cartwright, J. E. (2015) · American Journal Of Pathology · doi:10.1016/j.ajpath.2015.06.020 · Cited by 45 · see citing works
Prenatal exposure to triphenyl phosphate activated PPARγ in placental trophoblasts and impaired pregnancy outcomes
Hong, J., Jiang, M., Guo, L., Lin, J., Wang, Y., Tang, H., & Liu, X. (2022) · Environmental Pollution · doi:10.1016/j.envpol.2022.119039 · Cited by 45 · see citing works
Monitoring structural modulation of redox-sensitive proteins in cells with MS-CETSA
Sun, W., Dai, L., Yu, H., Puspita, B., Zhao, T., Li, F., Tan, J. L., Lim, Y. T., Chen, M. W., Sobota, R. M., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101168 · Cited by 45 · see citing works
Carotid chemoreceptor “resetting” revisited
Carroll, J. L., & Kim, I. (2012) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2012.09.002 · Cited by 44 · see citing works
“HIF can also be activated by non-O2-dependent mechanisms including growth factors, hormones and cytokines (Patel et al., 2010).”
Background
Two functional loci in the promoter of EPAS1 gene involved in high-altitude adaptation of Tibetans
Xu, X.-H., Huang, X.-W., Li, Q., Li, Y.-N., Wang, Y., Liu, C., Ma, Y., Liu, Q.-M., Sun, K., Qian, F., et al. (2014) · Scientific Reports · doi:10.1038/srep07465 · Cited by 41 · see citing works
Murine trophoblast-derived and pregnancy-associated exosome-enriched extracellular vesicle microRNAs: Implications for placenta driven effects on maternal physiology
Stefanski, A. L., Martinez, N., Peterson, L. K., Callahan, T. J., Treacy, E., Luck, M. E., Friend, S. F., Hermesch, A. C., Maltepe, E., Phang, T. L., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0210675 · Cited by 43 · see citing works
Adenosine A2areceptors and O2sensing in development
Koos, B. J. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00664.2010 · Cited by 43 · see citing works
ITE and TCDD Differentially Regulate the Vascular Remodeling of Rat Placenta via the Activation of AhR
Wu, Y., Chen, X., Zhou, Q., He, Q., Kang, J., Zheng, J. J., Wang, K., & Duan, T. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086549 · Cited by 39 · see citing works
Biochemical and Morphological Effects of Hypoxic Environment on Human Embryonic Stem Cells in Long-Term Culture and Differentiating Embryoid Bodies
Lim, H., Han, J., Woo, D., Kim, S. E., Kim, S., Kang, H., & Kim, J. (2011) · Molecules and Cells · doi:10.1007/s10059-011-0016-8 · Cited by 38 · see citing works
“Nevertheless, it was previously shown that hypoxia stimulates the proliferation of trophoblast giant cells, which form the outer layer of the placenta (Jaffe et al., 1997; Patel et al., 2010; Pringle et al., 2010).”
Background
The influence of prenatal exercise and pre-eclampsia on maternal vascular function
Skow, R. J., King, E. C., Steinback, C. D., & Davenport, M. H. (2017) · Clinical Science · doi:10.1042/cs20171036 · Cited by 40 · see citing works
Household air pollution and chronic hypoxia in the placenta of pregnant Nigerian women: A randomized controlled ethanol Cookstove intervention
Dutta, A., Khramtsova, G. F., Brito, K., Alexander, D., Mueller, A., Chinthala, S., Adu, D., Ibigbami, T., Olamijulo, J., Odetunde, A., et al. (2017) · The Science of The Total Environment · doi:10.1016/j.scitotenv.2017.11.091 · Cited by 38 · see citing works
Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies
Stanek, J. W., & Biesiada, J. (2012) · Human Pathology · doi:10.1016/j.humpath.2011.03.012 · Cited by 37 · see citing works
Enhanced HIF2α expression during human trophoblast differentiation into syncytiotrophoblast suppresses transcription of placental growth factor
Fujii, T., Nagamatsu, T., Morita, K., Schust, D. J., Iriyama, T., Komatsu, A., Osuga, Y., & Fujii, T. (2017) · Scientific Reports · doi:10.1038/s41598-017-12685-w · Cited by 36 · see citing works
Molecular determinants of microvascular dysfunction in hypertensive pregnancy and preeclampsia
Yu, W., Gao, W. D., Rong, D., Wu, Z., & Khalil, R. A. (2018) · Microcirculation · doi:10.1111/micc.12508 · Cited by 36 · see citing works
Maternal stress in relation to sex-specific expression of placental genes involved in nutrient transport, oxygen tension, immune response, and the glucocorticoid barrier
Cowell, W., Deyssenroth, M. A., Chen, J., & Wright, R. J. (2020) · Placenta · doi:10.1016/j.placenta.2020.05.004 · Cited by 36 · see citing works
“Elevated levels of placental HIFs beyond the first trimester have also been associated with pre-eclampsia, pregnancy loss, and fetal growth restriction [45], with limited research supporting sexually dimorphic relationships [46].”
Background
Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts
Alves, P., Amaral, C., Teixeira, N. A. A., & Correia‐da‐Silva, G. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-03122-z · Cited by 32 · see citing works
Expression of hypoxia-regulated genes and glycometabolic genes in placenta from patients with intrahepatic cholestasis of pregnancy
Wei, W., & Hu, Y. (2014) · Placenta · doi:10.1016/j.placenta.2014.06.372 · Cited by 32 · see citing works
Cell Free Expression of hif1α and p21 in Maternal Peripheral Blood as a Marker for Preeclampsia and Fetal Growth Restriction
Ashur‐Fabian, O., Yerushalmi, G., Mazaki‐Tovi, S., Steinberg, D. M., Goldshtein, I., Yackobovitch‐Gavan, M., Schiff, E., Amariglio, N., & Rechavi, G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037273 · Cited by 32 · see citing works
“In addition, hif1a regulates TGFb3, a target gene induced by hypoxia both in vivo and in vitro in trophoblast cells [14,15,16,17].”
Background
Effect of oxygen on multidrug resistance in term human placenta
Javam, M., Audette, M. C., Iqbal, M., Bloise, E., Gibb, W., & Matthews, S. G. (2014) · Placenta · doi:10.1016/j.placenta.2014.02.010 · Cited by 31 · see citing works
“This leads to the flow of maternal blood into the intervillous space and a dramatic increase in oxygen levels for the remainder of pregnancy (w8% O2) [10].”
BackgroundInfluential
The metabolic characteristic of decidual immune cells and their unique properties in pregnancy loss*
Zhang, T., Shen, H., Qin, X., & Li, M. (2022) · Immunological Reviews · doi:10.1111/imr.13085 · Cited by 31 · see citing works
Screening Candidate Genes Regulating Placental Development from Trophoblast Transcriptome at Early Pregnancy in Dazu Black Goats (Capra hircus)
Luo, N., Cheng, W., Zhou, Y., Gu, B., Zhao, Z., & Zhao, Y. (2021) · Animals · doi:10.3390/ani11072132 · Cited by 31 · see citing works
“It suggested the low oxygen consumption and inhibition of mitochondrial function in early pregnancy [12,60].”
Background
Regulation of Placental Efflux Transporters during Pregnancy Complications
Kozlosky, D., Barrett, E. S., & Aleksunes, L. M. (2022) · Drug Metabolism and Disposition · doi:10.1124/dmd.121.000449 · Cited by 30 · see citing works
Placental Underperfusion in a Rat Model of Intrauterine Growth Restriction Induced by a Reduced Plasma Volume Expansion
Bibeau, K., Sicotte, B., Béland, M., Bhat, M., Gaboury, L. A., Couture, R., St‐Louis, J., & Brochu, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0145982 · Cited by 30 · see citing works
Maternal exercise during pregnancy reduces the risk of preterm birth through the mediating role of placenta
Huang, L., Fan, L., Ding, P., He, Y., Xie, C., Niu, Z., Tian, F., Yuan, S., Jia, D., & Chen, W. (2017) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2017.1372415 · Cited by 29 · see citing works
“For one thing, maternal exercise during pregnancy diverts blood toward muscles and skin and decreases utero placental perfusion intermittently, which built transient and relatively hypoxic milieu, thereby promoting angiogenesis and forming a good maternal–fetal vascular interface [36,37].”
Background
The association of the placental Hypoxia-inducible factor1-α polymorphisms and HIF1-α mRNA expression with preeclampsia
Harati‐Sadegh, M., Kohan, L., Teimoori, B., Mehrabani, M., & Salimi, S. (2018) · Placenta · doi:10.1016/j.placenta.2018.05.005 · Cited by 29 · see citing works
Distinct roles of HIF1A in endothelial adaptations to physiological and ambient oxygen
Jiang, Y., Li, Y., Wang, K., Dai, C., Huang, S., Chen, D., & Zheng, J. J. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.04.008 · Cited by 30 · see citing works
“Moreover, since many peptide factors such as rennin/angiotensin, cytokines and growth factors have been reported to regulate HIF1A expression in placenta via the oxygen-dependent or -independent mechanisms [39], we also cannot exclude the possibility that these peptide factors play roles in maintaining relatively high…”
Background
Evaluation of maternal serum hypoxia inducible factor-1α, progranulin and syndecan-1 levels in pregnancies with early- and late-onset preeclampsia
Davutoğlu, E. A., Fırat, A. A., Özel, A., Yılmaz, N., Uzun, I., Yüksel, İ. T., & Madazlı, R. (2017) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2017.1333098 · Cited by 29 · see citing works
“Nowadays there is growing evidence that HIF-1a can also be induced by oxygen-independent mechanisms like hormones, cytokines, or growth factors under normoxic conditions [8,10].”
Background
Aquaporins in Fetal Development
Martínez, N., & Damiano, A. E. (2017) · Advances in experimental medicine and biology · doi:10.1007/978-94-024-1057-0_13 · Cited by 28 · see citing works
Role of oxygen in fetoplacental endothelial responses: hypoxia, physiological normoxia, or hyperoxia?
Zhou, C., Zou, Q., Jiang, Y.-Z., & Zheng, J. J. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00528.2019 · Cited by 27 · see citing works
Increased maternal serum aquaporin‐9 expression in pregnancies complicated with early‐onset preeclampsia
Ölmez, F., Oğlak, S. C., & Özköse, Z. G. (2021) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.15129 · Cited by 28 · see citing works
“adaptation to fluctuations in the oxygen tensions.(24)”
O-GlcNAc cycling enzymes control vascular development of the placenta by modulating the levels of HIF-1α
Yang, Y. R., Jang, H., Lee, Y. H., Kim, I. S., Lee, H., Ryu, S. H., & Suh, P. (2015) · Placenta · doi:10.1016/j.placenta.2015.08.001 · Cited by 28 · see citing works
Expression and uptake of the thyroxine-binding protein transthyretin is regulated by oxygen in primary trophoblast placental cells
Patel, J., Landers, K. A., Mortimer, R. H., & Richard, K. (2012) · Journal of Endocrinology · doi:10.1530/joe-11-0348 · Cited by 26 · see citing works
Self-citation
Expression of aquaporin-3 (AQP3) in placentas from pregnancies complicated by preeclampsia
Szpilbarg, N., & Damiano, A. E. (2017) · Placenta · doi:10.1016/j.placenta.2017.09.010 · Cited by 27 · see citing works
Oxygen tension modulates AQP9 expression in human placenta
Castro-Parodi, M., Szpilbarg, N., Dietrich, V. C., Sordelli, M. S., Reca, A., Abán, C. E., Maskin, B. C., Farina, M., & Damiano, A. E. (2013) · Placenta · doi:10.1016/j.placenta.2013.04.017 · Cited by 27 · see citing works
Cigarette Smoke Extract Activates Hypoxia-Inducible Factors in a Reactive Oxygen Species-Dependent Manner in Stroma Cells from Human Endometrium
Kida, N., Matsuo, Y., Hashimoto, Y. K., Nishi, K., Tsuzuki‐Nakao, T., Bono, H. U., Maruyama, T., Hirota, K., & Okada, H. (2021) · Antioxidants · doi:10.3390/antiox10010048 · Cited by 24 · see citing works
SLC9B1 methylation predicts fetal intolerance of labor
Knight, A. K., Conneely, K. N., Kilaru, V., Cobb, D. O., Payne, J. L., Meilman, S., Corwin, E. J., Kaminsky, Z. A., Dunlop, A. L., & Smith, A. K. (2017) · Epigenetics · doi:10.1080/15592294.2017.1411444 · Cited by 24 · see citing works
“In normal pregnancy, HIF-1 is rapidly degraded [24].”
Background
NFAT5 Is Up-Regulated by Hypoxia: Possible Implications in Preeclampsia and Intrauterine Growth Restriction1
Dobierzewska, A., Palominos, M., Irarrázabal, C. E., Sánchez, M., Lozano, M., Pérez‐Sepúlveda, A., Monteiro, L. J., Burmeister, Y., Horacio Figueroa, D., Rice, G. E., et al. (2015) · Biology of Reproduction · doi:10.1095/biolreprod.114.124644 · Cited by 23 · see citing works
“For instance, the role of HIF1A, a master regulator of hypoxia response, in placental development is well characterized and has been assessed by using different in vivo experimental animal models [3, 33].”
Background
Ischemia-modified albumin as an oxidative stress biomarker in early pregnancy loss
Cengiz, H., Dağdeviren, H., Kanawati, A., Çaypınar, S. S., Yeşil, A., Ekin, M., & Yaşar, L. (2015) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.3109/14767058.2015.1061494 · Cited by 22 · see citing works
Study on the Expressions of PHD and HIF in Placentas from Normal Pregnant Women and Patients with Preeclampsia
Liu, W., Wang, S., & Lin, Q. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.6375 · Cited by 21 · see citing works
“HIF is highly expressed in the low oxygen environment of the placenta in early gestation, playing an important role in placental development and function [8].”
Background
Moderate Hypoxia Down-Regulates Interleukin-6 Secretion and TLR4 Expression in Human Sw.71 Placental Cells
Shirasuna, K., Shimamura, N., Seno, K., Ohtsu, A., Shiratsuki, S., Ohkuchi, A., Suzuki, H., Matsubara, S., Nagayama, S., Iwata, H., et al. (2015) · Cellular Physiology and Biochemistry · doi:10.1159/000430181 · Cited by 20 · see citing works
Expression of hypoxia-inducible factors and vascular endothelial growth factor during pregnancy in the feline uterus
AĞAOĞLU, Ö. K., Ağaoğlu, A. R., Güzeloğlu, A., Kurar, E., Kayış, S. A., Özmen, Ö., Schäfer–Somi, S., & Aslan, S. (2015) · Theriogenology · doi:10.1016/j.theriogenology.2015.02.009 · Cited by 19 · see citing works
Changes in reactive oxygen species, superoxide dismutase, and hypoxia-inducible factor-1α levels in missed abortion.
Zhu, L.-J., Chen, Y., Chen, B.-J., & Mei, X.-H. (2014) · Europe PMC (PubMed Central) · Cited by 19 · see citing works
The paradoxical pro‐ and antiangiogenic actions of resveratrol: therapeutic applications in cancer and diabetes
Kamaleddin, M. A. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13283 · Cited by 18 · see citing works
Use of infrared microspectroscopy to elucidate a specific chemical signature associated with hypoxia levels found in glioblastoma
Sandt, C., Nadaradjane, C., Richards, R., Dumas, P., & Sée, V. (2015) · The Analyst · doi:10.1039/c5an02112j · Cited by 18 · see citing works
Induction of hypoxia-inducible factor-1α by BDNF protects retinoblastoma cells against chemotherapy-induced apoptosis
Gao, Y., Ming, J., Ge, R., & Lang, L.-L. (2016) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-016-2660-y · Cited by 17 · see citing works
“However, HIF-1a could also be activated in many solid tumors by many growth factors under normoxic conditions [27].”
Genome-Wide Analysis of Hypoxia-Inducible Factor Binding Reveals Targets Implicated in Impaired Human Placental Syncytiotrophoblast Formation under Low Oxygen
Jaremek, A., Shaha, S. Z., Jeyarajah, M. J., Bhattad, G. J., Chowdhury, D., Riddell, M. R., & Renaud, S. J. (2023) · American Journal Of Pathology · doi:10.1016/j.ajpath.2023.03.006 · Cited by 16 · see citing works
The effect of histone deacetylase inhibition on the expression of P-glycoprotein in human placental trophoblast cell lines
Duan, H., Wang, C., Zhou, K., Wang, T., Li, Y., Qiu, D., Li, Q., Zhang, Y., & Hua, Y. (2016) · Placenta · doi:10.1016/j.placenta.2016.11.011 · Cited by 16 · see citing works
Hypoxia‐induced SPOP attenuates the mobility of trophoblast cells through inhibition of the PI3K/AKT/GSK3β pathway
Yuan, D., Yang, Z., Chen, Y., Li, S., Tan, B., & Yu, Q. (2020) · Cell Biology International · doi:10.1002/cbin.11501 · Cited by 16 · see citing works
“Studies have proved that the BTB domain could bind to the ubiquitin ligase cullin3 and act as a sub- strate adapter between Cul3 and a specific substrate (Lionel Pintard et al., 2003; Rory et al., 2003).”
Background
Occupational exposure to pesticides in female tea garden workers and adverse birth outcomes
Kumar, S. N., Vaibhav, K., Bastia, B., Singh, V., Ahluwalia, M., Agrawal, U., Borgohain, D., Raisuddin, S., & Jain, A. K. (2020) · Journal of Biochemical and Molecular Toxicology · doi:10.1002/jbt.22677 · Cited by 16 · see citing works
Structural changes, increased hypoxia, and oxidative DNA damage in placenta due to maternal smokeless tobacco use
Kumar, S. N., Bastia, B., Borgohain, D., Agrawal, U., Raisuddin, S., & Jain, A. K. (2021) · Birth Defects Research · doi:10.1002/bdr2.1941 · Cited by 15 · see citing works
Fetal Oxygenation from the 23rd to the 36th Week of Gestation Evaluated through the Umbilical Cord Blood Gas Analysis
Filippi, L., Pascarella, F., Pini, A., Cammalleri, M., Bagnoli, P., Morganti, R., Innocenti, F., Castagnini, N., Melosi, A., & Scaramuzzo, R. T. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512487 · Cited by 15 · see citing works
“Although HIF is regulated also through oxygen-independent mechanisms such as hormones (angiotensin II), cytokines (interleukin1β, tumor necrosis factor α, and NF-kβ), or growth factors (transforming growth factor-β1 and insulin-like growth factor), all of which are significantly upregulated during pregnancy [23], oxyg…”
Background
The potential association between a new angiogenic marker fractalkine and a placental vascularization in preeclampsia
Szewczyk, G., Pyźlak, M., Pankiewicz, K., Szczerba, E., Stangret, A., Szukiewicz, D., Skoda, M., Bierła, J. B., Cukrowská, B., & Fijałkowska, A. (2021) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-021-05966-3 · Cited by 15 · see citing works
Controlling Trophoblast Cell Fusion in the Human Placenta—Transcriptional Regulation of Suppressyn, an Endogenous Inhibitor of Syncytin-1
Sugimoto, J., Schust, D. J., Sugimoto, M., Jinno, Y., & Kudo, Y. (2023) · Biomolecules · doi:10.3390/biom13111627 · Cited by 14 · see citing works
“To this point, previous studies have reported important roles of HIF1 α and HIF2 α in trophoblast syncytialization [43,44] and cytotrophoblast differentiation.”
Result
Oxygen regulation of aquaporin-4 in human placenta
Szpilbarg, N., Seyahian, A., Paola, M. D., Castro-Parodi, M., Martínez, N., Farina, M., & Damiano, A. E. (2018) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2018.08.015 · Cited by 14 · see citing works
Mechanisms of fetal epigenetics that determine telomere dynamics and health span in adulthood
Ravlić, S., Vidaček, N. Š., Nanić, L., Laganović, M., Slade, N., Jelaković, B., & Rubelj, I. (2017) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2017.08.014 · Cited by 12 · see citing works
“which regulate placental function (Patel et al., 2010).”
Low oxygen tension differentially regulates the expression of placental solute carriers and ABC transporters
Gorczyca, L., Du, J., Bircsak, K. M., Wen, X., Vetrano, A. M., & Aleksunes, L. M. (2020) · FEBS Letters · doi:10.1002/1873-3468.13937 · Cited by 12 · see citing works
The mediating role of placenta in the relationship between maternal exercise during pregnancy and full-term low birth weight
Huang, L., Fan, L., Ding, P., He, Y., Xie, C., Niu, Z., Tian, F., Yuan, S., Jia, D., & Chen, W. (2017) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2017.1319936 · Cited by 12 · see citing works
“placental vascular endothelial growth factor, thereby promoting angiogenesis and forming a good utero–fetal circulation [29].”
Background
New Insights Into the Role of Placental Aquaporins and the Pathogenesis of Preeclampsia
Szpilbarg, N., Martínez, N., Paola, M. D., Reppetti, J., Medina, Y., Seyahian, A., Castro-Parodi, M., & Damiano, A. E. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01507 · Cited by 12 · see citing works
Glycosylation Profile of the Transferrin Receptor in Gestational Iron Deficiency and Early-Onset Severe Preeclampsia
Gómez-Gutiérrez, A. M., Parra-Sosa, B. E., & Bueno-Sánchez, J. C. (2019) · Journal of Pregnancy · doi:10.1155/2019/9514546 · Cited by 13 · see citing works
“Representatives images of Western Blot of TfR1 and HIF-1𝛼.”
BackgroundInfluential
From Molecules to Imaging: Assessment of Placental Hypoxia Biomarkers in Placental Insufficiency Syndromes
Darwish, F. M. A., Meijerink, L., Coolen, B. F., Strijkers, G. J., Bekker, M. N., Lely, A. T., & Terstappen, F. (2023) · Cells · doi:10.3390/cells12162080 · Cited by 11 · see citing works
“Placental insufficiency is associated with pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), and stillbirth [1].”
Background
Low oxygen tension promotes invasive ability and embryo implantation rate
Bagheri, D., Kazemi, P., Sarmadi, F., Shamsara, M., Hashemi, E., Joupari, M. D., & Dashtizad, M. (2018) · Reproductive Biology · doi:10.1016/j.repbio.2018.05.003 · Cited by 11 · see citing works
Magnesium salts in pregnancy
Marı́n, R., Abad, C., Rojas, D., Chiarello, D. I., Rangel, H., Teppa-Garrán, A., Fernández, M., & Ruette, F. (2023) · Journal of Trace Elements and Minerals · doi:10.1016/j.jtemin.2023.100071 · Cited by 11 · see citing works
Placental NFE2L2 is discordantly activated in monochorionic twins with selective intrauterine growth restriction and possibly regulated by hypoxia
Wu, J., He, Z., Gao, Y., Zhang, G., Huang, X., & Fang, Q. (2017) · Free Radical Research · doi:10.1080/10715762.2017.1315113 · Cited by 11 · see citing works
“ated with placental dysfunction diseases [8].”
Seasonal and temporal variation in the placenta during melatonin supplementation in a bovine compromised pregnancy model
Contreras-Correa, Z. E., Cochran, T., Metcalfe, A., Burnett, D. D., & Lemley, C. O. (2022) · Journal of Animal Science · doi:10.1093/jas/skac372 · Cited by 10 · see citing works
Aquaporins during pregnancy
Damiano, A. E. (2020) · Vitamins and hormones · doi:10.1016/bs.vh.2019.08.009 · Cited by 10 · see citing works
Prenatal exercise reprograms the development of hypertension progress and improves vascular health in SHR offspring
Li, S., Chen, Y., Zhang, Y., Qiu, F., Zeng, F., & Shi, L. (2021) · Vascular Pharmacology · doi:10.1016/j.vph.2021.106885 · Cited by 10 · see citing works

Beyond oxygen: complex regulation and activity of hypoxia inducible factors in pregnancy
Pringle, K. G., Kind, K. L., Sferruzzi-Perri, A. N., Thompson, J. G., & Roberts, C. T. (2010) · Human Reproduction Update · doi:10.1093/humupd/dmp046 · Cited by 259 · see citing works
Hypoxia, HIF and the Placenta
Fryer, B. H., & Simon, M. C. (2006) · Cell Cycle · doi:10.4161/cc.5.5.2497 · Cited by 75 · see citing works
Hypoxia induced HIF-1/HIF-2 activity alters trophoblast transcriptional regulation across gestation
Sultana, M.-E. K. (2015) · Adelaide Research & Scholarship (AR&S) (University of Adelaide)
Hypoxia and human placental development
Aplin, J. (2000) · Journal of Clinical Investigation · doi:10.1172/jci9512 · Cited by 68 · see citing works
Dynamic HIF1A Regulation During Human Placental Development1
Ietta, F., Wu, Y., Winter, J., Xu, J., Wang, J., Post, M., & Caniggia, I. (2006) · Biology of Reproduction · doi:10.1095/biolreprod.106.051557 · Cited by 127 · see citing works

Authors: Patel, J., Landers, K., Mortimer, R. H., & Richard, K.
Affiliations: The University of Queensland (AU)
Royal Brisbane and Women's Hospital (AU)
Corresponding author: Patel, J.
ORCID: Patel, J.
Landers, K.
Mortimer, R.H.
Richard, K.
Venue: Placenta
Publisher: Elsevier BV
Published: 2010-11
Volume: 31
Issue: 11
Pages: 951-957
ISSN: 0143-4004 (ISSN-L)
DOI: 10.1016/j.placenta.2010.08.008
OpenAlex: W2073204295
Cited by: 157
References: 80
Citations by year: 2026: 9 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 9 · 2021: 13 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 18 · 2016: 7 · 2015: 14 · 2014: 12 · 2013: 9 · 2012: 18
FWCI: 1.70
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Placenta (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
Keywords: hypoxia-inducible factor, placental development, placental hypoxia, extravillous trophoblast, angiogenesis, renin-angiotensin system, cytokines, growth factors, first trimester, placental differentiation, hypoxia-ischemia
MeSH terms: Endothelial PAS Domain-Containing Protein 1, Animals, Female, Humans, Placentation, Pregnancy, Repressor Proteins, Signal Transduction, Cell Hypoxia, Gene Expression Regulation, Developmental, Apoptosis Regulatory Proteins, Aryl Hydrocarbon Receptor Nuclear Translocator, Basic Helix-Loop-Helix Transcription Factors, 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

Regulation of Hypoxia Inducible Factors (HIF) in Hypoxia and Normoxia During Placental Development

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks