Dynamic HIF1A Regulation During Human Placental Development1
Abstract
The human placenta is a unique organ in terms of oxygenation as it undergoes a transition from a low to a more oxygenated environment. This physiological switch in oxygen tension is a prerequisite for proper placental development and involves the hypoxia inducible factor (HIF). HIF is stable and initiates gene transcription under hypoxia, whereas in normoxia, interaction with the von Hippel-Lindau tumor suppressor protein (VHL) leads to rapid degradation of the HIF1A subunit. The degradation requires formation of a multiprotein complex (VHLCBC) and hydroxylation of HIF1A proline residues via members of the egg-laying-defective nine (EGLN) family. Herein, we have investigated the regulatory mechanisms of HIF1A expression during human placental development. Expression of HIF1A and VHL was high at 7-9 wk of gestation, when oxygen tension is low, and decreased when placental oxygen tension increases (10-12 wk of gestation). During early placentation, HIF1A localized in cytotrophoblasts, while VHL was present in syncytiotrophoblasts. At 10-12 wk, VHL appeared in cytotrophoblast cells, which coincided with the disappearance of HIF1A. At the same time the association of VHL and Cullin 2 as well as ubiquitination of HIF1A was maximal. EGLN1, EGLN2, and EGLN3 were also temporally expressed in an oxygen-dependent fashion, with greatest mRNA expression at 10-12 wk of gestation. Inhibition of EGLN activity increased HIF1A stability in villous explants and stimulated transforming growth factor beta 3 (TGFB3) expression consistent with promoter analyses showing that HIF1A transactivates TGFB3. These data demonstrate that during placental development, HIF1A is regulated by temporal and spatial changes in expression and association of molecules forming the multi-protein VHLCBC complex as well as prolyl hydroxylase activities.
Integrity signals
Registry
Cites
Statistics
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?
Ontogenetic studies have reported contrasting results, with peaks of HIF-1α at 7-10 weeks and then again at 14-18 weeks, or a steady decline in HIF-1α from 5-8 weeks to 18-21 weeks and a rapid decline of HIF-2α between 5-8 weeks and 9-11 weeks.
“Ontogenetic studies have reported contrasting results, with peaks of HIF-1α at 7-10 weeks and then again at 14-18 weeks (269), or a steady decline in HIF-1α from 5-8 weeks to 18-21 weeks and a rapid decline of HIF-2α between 5-8 weeks and 9-11 weeks (447).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [269]
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
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 · see citing works
The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis
Maxwell, P. H., Wiesener, M. S., Chang, G.-W., Clifford, S. C., Vaux, E. C., Cockman, M. E., Wykoff, C. C., Pugh, C. W., Maher, E. R., & Ratcliffe, P. J. (1999) · Nature · doi:10.1038/20459 · Cited by 5,180 · see citing works
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
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 · see citing works
Ohh, M., Park, C. W., Ivan, M., Hoffman, M. A., Kim, T.-Y., Huang, L. E., Pavletich, N., Chau, V., & Kaelin, W. G. (2000) · Nature Cell Biology · doi:10.1038/35017054 · Cited by 1,577 · see citing works
Mahon, P. C., Hirota, K., & Semenza, G. L. (2001) · Genes & Development · doi:10.1101/gad.924501 · Cited by 1,385 · see citing works
Berra, E., Benizri, E., Ginouvès, A., Volmat, V., Roux, D., & Pouysségur, J. (2003) · The EMBO Journal · doi:10.1093/emboj/cdg392 · Cited by 1,348 · see citing works
Appelhoff, R. J., Tian, Y.-M., Raval, R. R., Turley, H., Harris, A. L., Pugh, C. W., Ratcliffe, P. J., & Gleadle, J. M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406026200 · Cited by 1,108 · see citing works
Cockman, M. E., Masson, N., Mole, D. R., Jaakkola, P., Chang, G.-W., Clifford, S. C., Maher, E. R., Pugh, C. W., Ratcliffe, P. J., & Maxwell, P. H. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002740200 · Cited by 1,053 · 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
Fukuda, R., Hirota, K., Fan, F., Jung, Y. D., Ellis, L. M., & Semenza, G. L. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203781200 · Cited by 815 · 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
Stroka, D., Burkhardt, T., Desbaillets, I., Wenger, R. H., Neil, D., Bauer, C., GASSMANN, M., & Candinas, D. (2001) · The FASEB Journal · doi:10.1096/fj.01-0125com · Cited by 716 · see citing works
Binding of the von Hippel-Lindau Tumor Suppressor Protein to Elongin B and C
Kibel, A. S., Iliopoulos, O., DeCaprio, J. A., & Kaelin, W. G. (1995) · Science · doi:10.1126/science.7660130 · Cited by 664 · see citing works
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
Self-citationRichard, D. E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003325200 · Cited by 584 · 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
Genbačev, O., Joslin, R. J., Damsky, C. H., Polliotti, B., & Fisher, S. J. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118447 · Cited by 573 · see citing works
Ivan, M., Haberberger, T., Gervasi, D. C., Michelson, K. S., Günzler, V., Kondo, K., Yang, H., Sorokina, I., Conaway, R. C., Conaway, J. W., et al. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192342099 · Cited by 561 · see citing works
Characterization of NEDD8, a Developmentally Down-regulated Ubiquitin-like Protein
Kamitani, T., Kito, K., Nguyen, H. P., & Yeh, E. T. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28557 · Cited by 535 · see citing works
Richard, D. E., Berra, E., & Pouysségur, J. (2000) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)61441-9 · Cited by 488 · see citing works
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
Intracellular localisation of human HIF-1α hydroxylases:implications for oxygen sensing
Metzen, E., Berchner-Pfannschmidt, U., Stengel, P., Marxsen, J. H., Stolze, I., Klinger, M., Huang, W. Q., Wotzlaw, C., Hellwig-Bürgel, T., Jelkmann, W., et al. (2003) · Journal of Cell Science · doi:10.1242/jcs.00318 · Cited by 432 · see citing works
Caniggia, I., Winter, J., Lye, S. J., & Post, M. (2000) · Placenta · doi:10.1053/plac.1999.0522 · Cited by 377 · see citing works
Self-citationCaniggia, 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
Self-citationMottet, D., Dumont, V., Deccache, Y., Demazy, C., Ninane, N., Raes, M. J., & Michiels, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300763200 · Cited by 316 · see citing works
Hypoxia Up-regulates Prolyl Hydroxylase Activity
D’Angelo, G., Duplan, E., Boyer, N., Vigne, P., & Frelin, C. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m302244200 · Cited by 285 · see citing works
Iliopoulos, O., Ohh, M., & Kaelin, W. G. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11661 · Cited by 266 · see citing works
The von Hippel–Lindau tumor suppressor gene is required for cell cycle exit upon serum withdrawal
Pause, A., Lee, S., Lonergan, K. M., & Klausner, R. D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.3.993 · Cited by 237 · see citing works
Mammalian <i>EGLN</i> genes have distinct patterns of mRNA expression and regulation
Lieb, M. E., Menzies, K., Moschella, M. C., Ni, R., & Taubman, M. B. (2002) · Biochemistry and Cell Biology · doi:10.1139/o02-115 · Cited by 186 · see citing works
An intact NEDD8 pathway is required for Cullin‐dependent ubiquitylation in mammalian cells
Ohh, M., Kim, W. Y., Moslehi, J. J., Chen, Y., Chau, V., Read, M. A., & Kaelin, W. G. (2002) · EMBO Reports · doi:10.1093/embo-reports/kvf028 · Cited by 177 · see citing works
Cioffi, C. L., Liu, X., Kosinski, P. A., Garay, M., & Bowen, B. R. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)00453-4 · Cited by 170 · see citing works
Stolze, I. P., Tian, Y.-M., Appelhoff, R. J., Turley, H., Wykoff, C. C., Gleadle, J., & Ratcliffe, P. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m406713200 · Cited by 155 · see citing works
Liakopoulos, D., Büsgen, T., Brychzy, A., Jentsch, S., & Pause, A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5510 · Cited by 112 · see citing works
Hypoxia-Inducible Factor-1 Transactivates Transforming Growth Factor-β3 in Trophoblast
Nishi, H., Nakada, T., Hokamura, M., Osakabe, Y., 糸数, 修., Huang, E. L., & Isaka, K. (2004) · Endocrinology · doi:10.1210/en.2003-1639 · Cited by 95 · see citing works
Genbačev, O., Krtolica, A., Kaelin, W. G., & Fisher, S. J. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0231 · Cited by 83 · see citing works
Focal Adhesion Kinase Is a Key Mediator of Human Trophoblast Development
MacPhee, D. J., Mostachfi, H., Han, R. N. N., Lye, S. J., Post, M., & Caniggia, I. (2001) · Laboratory Investigation · doi:10.1038/labinvest.3780362 · Cited by 78 · see citing works
Self-citationOxygen-regulated Expression of TGF-β3, a Growth Factor Involved in Trophoblast Differentiation
Schäffer, L., Scheid, A., Spielmann, P., Breymann, C., Zimmermann, R., Meuli, M., Gassmann, M., Marti, H. H., & Wenger, R. H. (2003) · Placenta · doi:10.1016/s0143-4004(03)00166-8 · Cited by 72 · see citing works
Haddad, J. J. (2003) · PubMed · Cited by 63 · see citing works
Murata, H., Tajima, N., Nagashima, Y., Yao, M., Baba, M., Goto, M., Kawamoto, S., Yamamoto, I., Okuda, K., & Kanno, H. (2002) · PubMed · Cited by 34 · see citing works
Flagged first, then by citations
Cited by
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
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
Low chorionic villous succinate accumulation associates with recurrent spontaneous abortion risk
Wang, X.-H., Xu, S., Zhou, X., Zhao, R., Lin, Y., Cao, J., Zang, W., Tao, H., Xu, W., Li, M., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-23827-0 · Cited by 164 · see citing works
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 · Cited by 157 · see citing works
Hypoxia and Placental Development
Soares, M. J., Iqbal, K., & Kozai, K. (2017) · Birth Defects Research · doi:10.1002/bdr2.1135 · Cited by 148 · see citing works
Disruption of sphingolipid metabolism augments ceramide-induced autophagy in preeclampsia
Melland‐Smith, M., Ermini, L., Chauvin, S., Craig-Barnes, H. A., Tagliaferro, A., Todros, T., Post, M., & Caniggia, I. (2015) · Autophagy · doi:10.1080/15548627.2015.1034414 · Cited by 150 · see citing works
Self-citationManna, S., McCarthy, C., & McCarthy, F. P. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/3095383 · Cited by 141 · see citing works
Zamudio, S., Wu, Y., Ietta, F., Rolfo, A., Cross, A., Wheeler, T., Post, M., Illsley, N. P., & Caniggia, I. (2007) · The American Journal of Pathology · doi:10.2353/ajpath.2007.061185 · Cited by 124 · see citing works
Self-citationDevelopmental cell biology of human villous trophoblast: current research problems
Aplin, J. (2009) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082759ja · Cited by 123 · see citing works
Abnormalities in Oxygen Sensing Define Early and Late Onset Preeclampsia as Distinct Pathologies
Rolfo, A., Many, A., Racano, A., Tal, R., Tagliaferro, A., Ietta, F., Wang, J., Post, M., & Caniggia, I. (2010) · PLoS ONE · doi:10.1371/journal.pone.0013288 · Cited by 112 · see citing works
Self-citationSevere Intrauterine Growth Restriction Pregnancies Have Increased Placental Endoglin Levels
Yinon, Y., Nevo, O., Xu, J., Many, A., Rolfo, A., Todros, T., Post, M., & Caniggia, I. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2008.070640 · Cited by 110 · see citing works
Self-citationIllsley, N. P., Caniggia, I., & Zamudio, S. (2010) · The International Journal of Developmental Biology · doi:10.1387/ijdb.082798ni · Cited by 107 · see citing works
Self-citationThe Role of NFκB in Healthy and Preeclamptic Placenta: Trophoblasts in the Spotlight
Armistead, B., Kadam, L., Drewlo, S., & Kohan‐Ghadr, H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21051775 · Cited by 89 · see citing works
Oxygenation of the placental–fetal unit in humans
Schneider, H. (2011) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2011.05.009 · Cited by 84 · see citing works
The role of epigenetic changes in preeclampsia
Kamrani, A., Alipourfard, I., Ahmadi‐Khiavi, H., Yousefi, M., Rostamzadeh, D., Izadi, M., & Ahmadi, M. (2019) · BioFactors · doi:10.1002/biof.1542 · Cited by 85 · see citing works
Autophagy Induced by HIF1α Overexpression Supports Trophoblast Invasion by Supplying Cellular Energy
Tatematsu, M., Nakashima, A., Fujita, N., Shima, T., Yoshimori, T., & Saito, S. (2013) · PLoS ONE · doi:10.1371/journal.pone.0076605 · Cited by 78 · see citing works
Cindrova-Davies, T., van Patot, M. T., Gardner, L., Jauniaux, E., Burton, G. J., & Charnock-Jones, D. S. (2015) · MHR: Basic science of reproductive medicine · doi:10.1093/molehr/gau105 · Cited by 74 · see citing works
Grazul‐Bilska, A. T., Johnson, M. L., Borowicz, P. P., Minten, M. A., Bilski, J. J., Wróblewski, R., Velimirovich, M., Coupe, L. R., Redmer, D. A., & Reynolds, L. P. (2011) · Reproduction · doi:10.1530/rep-10-0505 · Cited by 73 · see citing works
Systematic Characterization of Autophagy in Gestational Diabetes Mellitus
Ji, L., Chen, Z., Xu, Y., Xiong, G., Liu, R., Wu, C., Hu, H., & Wang, L. (2017) · Endocrinology · doi:10.1210/en.2016-1922 · Cited by 72 · see citing works
Hypoxia-inducible Factors in the First Trimester Human Lung
Groenman, F. A., Rutter, M., Caniggia, I., Tibboel, D., & Post, M. (2006) · Journal of Histochemistry & Cytochemistry · doi:10.1369/jhc.6a7129.2006 · Cited by 71 · see citing works
Self-citationPlacental cytokines and preeclampsia
Keelan, J. A. (2006) · Frontiers in bioscience · doi:10.2741/2266 · Cited by 67 · see citing works
Effect of chemical stabilizers of hypoxia-inducible factors on early lung development
Groenman, F. A., Rutter, M., Wang, J., Caniggia, I., Tibboel, D., & Post, M. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00486.2006 · Cited by 66 · see citing works
Self-citationStejskalová, L., Vecerova, L., Peréz, L. M., Vrzal, R., Dvořák, Z., Nachtigal, P., & Pávek, P. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr150 · Cited by 55 · see citing works
Oxygen regulation of macrophage migration inhibitory factor in human placenta
Ietta, F., Wu, Y., Romagnoli, R., Soleymanlou, N., Orsini, B., Zamudio, S., Paulesu, L. R., & Caniggia, I. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00086.2006 · Cited by 52 · see citing works
Self-citationArchitecture 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
Mechanism of maternal vascular remodeling during human pregnancy
Sato, Y., Fujiwara, H., & Konishi, I. (2011) · Reproductive Medicine and Biology · doi:10.1007/s12522-011-0102-9 · Cited by 49 · see citing works
Jones, D. S. (2015) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2015.07.004 · Cited by 47 · see citing works
Down-regulation of the placental BCRP/ABCG2 transporter in response to hypoxia signaling
Francois, L., Gorczyca, L., Du, J., Bircsak, K. M., Yen, E., Wen, X., Tu, M., Yu, A., Illsley, N. P., Zamudio, S., et al. (2017) · Placenta · doi:10.1016/j.placenta.2017.01.125 · Cited by 44 · see citing works
Chauvin, S., Yinon, Y., Xu, J., Ermini, L., Sallais, J., Tagliaferro, A., Todros, T., Post, M., & Caniggia, I. (2015) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-1288 · Cited by 43 · see citing works
Self-citationThe Asparagine Hydroxylase FIH: A Unique Oxygen Sensor
Volkova, Y. L., Pickel, C., Jucht, A. E., Wenger, R. H., & Scholz, C. C. (2022) · Antioxidants and Redox Signaling · doi:10.1089/ars.2022.0003 · Cited by 42 · see citing works
Pávek, P., & Smutný, T. (2013) · Drug Metabolism Reviews · doi:10.3109/03602532.2013.835819 · Cited by 42 · see citing works
Zhu, J., Wang, K., Li, T., Chen, J., Xie, D., Chang, X., Yao, J., Wu, J., Zhou, Q., Jia, Y., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-07560-7 · Cited by 42 · see citing works
Glycolysis: A fork in the path of normal and pathological pregnancy
Gou, R., & Zhang, X. (2023) · The FASEB Journal · doi:10.1096/fj.202301230r · Cited by 40 · see citing works
Farrell, A., Alahari, S., Ermini, L., Tagliaferro, A., Litvack, M. L., Post, M., & Caniggia, I. (2019) · JCI Insight · doi:10.1172/jci.insight.127009 · Cited by 37 · see citing works
Self-citationLaquatra, C., Sànchez‐Martìn, C., Dinarello, A., Cannino, G., Minervini, G., Moroni, E., Schiavone, M., Tosatto, S. C. E., Argenton, F., Colombo, G., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03716-6 · Cited by 37 · see citing works
Current State of Preeclampsia Mouse Models: Approaches, Relevance, and Standardization
Waker, C. A., Kaufman, M. R., & Brown, T. L. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.681632 · Cited by 36 · see citing works
Hypoxia and Placental Remodelling
Cartwright, J. E., Keogh, R. J., & van Patot, M. C. T. (2007) · Advances in experimental medicine and biology · doi:10.1007/978-0-387-75434-5_9 · Cited by 36 · see citing works
Jumonji Domain Containing Protein 6: A Novel Oxygen Sensor in the Human Placenta
Alahari, S., Post, M., & Caniggia, I. (2015) · Endocrinology · doi:10.1210/en.2015-1262 · Cited by 36 · see citing works
Self-citationNishimura, R., & Okuda, K. (2015) · Reproduction Fertility and Development · doi:10.1071/rd15010 · Cited by 35 · see citing works
Meade, E., Ma, Y., & Guller, S. M. (2007) · Placenta · doi:10.1016/j.placenta.2007.04.005 · Cited by 35 · see citing works
Maternal iron homeostasis: effect on placental development and function
Roberts, H., Bourque, S. L., & Renaud, S. J. (2020) · Reproduction · doi:10.1530/rep-20-0271 · Cited by 34 · see citing works
Hypoxia and Preeclampsia: Increased Expression of Urocortin 2 and Urocortin 3
Imperatore, A., Rolfo, A., Petraglia, F., Challis, J. R. G., & Caniggia, I. (2010) · Reproductive Sciences · doi:10.1177/1933719110373147 · Cited by 32 · see citing works
Self-citationMcGillick, E. V., Orgeig, S., & Morrison, J. L. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00469.2015 · Cited by 32 · see citing works
Compromised JMJD6 Histone Demethylase Activity Affects VHL Gene Repression in Preeclampsia
Alahari, S., Post, M., Rolfo, A., Weksberg, R., & Caniggia, I. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-02197 · Cited by 30 · see citing works
Self-citationDistinct 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
Uteroplacental ischemia in early‐ and late‐onset pre‐eclampsia: a role for the fetus?
Espinoza, J. (2012) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.12280 · Cited by 29 · see citing works
VTA neurons show a potentially protective transcriptional response to MPTP
Phani, S., Gonye, G. E., & Iacovitti, L. (2010) · Brain Research · doi:10.1016/j.brainres.2010.04.061 · Cited by 28 · see citing works
Sallais, J., Park, C., Alahari, S., Porter, T. R., Liu, R., Kurt, M., Farrell, A., Post, M., & Caniggia, I. (2022) · JCI Insight · doi:10.1172/jci.insight.158908 · Cited by 27 · see citing works
Self-citationExpression of GRIM-19 in missed abortion and possible pathogenesis
Chen, H., Deng, X., Yang, Y., Shen, Y., Lan, C., Wen, Y., & Sun, Y. (2014) · Fertility and Sterility · doi:10.1016/j.fertnstert.2014.10.012 · Cited by 26 · see citing works
The double life of MULE in preeclamptic and IUGR placentae
Rolfo, A., Garcia, J., Todros, T., Post, M., & Caniggia, I. (2012) · Cell Death and Disease · doi:10.1038/cddis.2012.44 · Cited by 26 · see citing works
Self-citationPlacental HIFs as markers of cerebral hypoxic distress in fetal mice
Trollmann, R., Strasser, K., Keller, S., Antoniou, X., Grenacher, B., Ogunshola, O. O., Dötsch, J., Rascher, W., & Gassmann, M. (2008) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00053.2008 · Cited by 26 · see citing works
The Interplay of Molecular Factors and Morphology in Human Placental Development and Implantation
Vornic, I., Buciu, V. B., Furau, C. G., Zara, F., Novacescu, D., Barb, A. C., Cumpănaş, A. A., Latcu, S. C., Sas, I., Șerban, D. M., et al. (2024) · Biomedicines · doi:10.3390/biomedicines12122908 · Cited by 27 · see citing works
Na, K., Lee, H., Choi, J., -, J. E., Nam, S., Yoon, T. K., & Kim, G. I. J. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23398 · Cited by 25 · see citing works
Yang, H. J., Kim, T., An, B., Choi, K., Lee, H., Kim, J., & Jeung, E. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.12.012 · Cited by 23 · see citing works
Ayele, F. T., Biedrzycki, R. J., Habtewold, T. D., Wijesiriwardhana, P., Burt, A., Marsit, C. J., Ouidir, M., & Wapner, R. J. (2025) · Nature Communications · doi:10.1038/s41467-025-58128-3 · Cited by 21 · see citing works
Liu, W., Wang, S., & Lin, Q. (2014) · International Journal of Biological Sciences · doi:10.7150/ijbs.6375 · Cited by 21 · see citing works
Liao, T.-L., Chen, S., Tzeng, C.-R., & Kao, S. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151017733 · Cited by 20 · see citing works
Patel, J., Landers, K., Li, H., Mortimer, R. H., & Richard, K. (2010) · Placenta · doi:10.1016/j.placenta.2010.11.016 · Cited by 20 · see citing works
Regulation by hypoxia of adrenomedullin output and expression in human trophoblast cells
Marinoni, E., Pacioni, K., Sambuchini, A., Moscarini, M., Letizia, C., & Iorio, R. D. (2010) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2010.10.013 · Cited by 19 · see citing works
Zhu, L.-J., Chen, Y., Chen, B.-J., & Mei, X.-H. (2014) · Europe PMC (PubMed Central) · Cited by 19 · see citing works
Depoix, C. L., de Selliers, I., Hubinont, C., & Debiève, F. (2017) · Molecular Human Reproduction · doi:10.1093/molehr/gax002 · Cited by 19 · see citing works
Vrijens, K., Tsamou, M., Madhloum, N., Gyselaers, W., & Nawrot, T. S. (2018) · Journal of Translational Medicine · doi:10.1186/s12967-017-1375-5 · Cited by 19 · see citing works
Dynamic regulation of HIF1Α stability by SUMO2/3 and SENP3 in the human placenta
Bhattacharjee, J., Alahari, S., Sallais, J., Tagliaferro, A., Post, M., & Caniggia, I. (2016) · Placenta · doi:10.1016/j.placenta.2016.02.002 · Cited by 18 · see citing works
Self-citationInvolvement of the AHR in Development and Functioning of the Female and Male Reproductive Systems
Karman, B. N., Hernández‐Ochoa, I., Ziv‐Gal, A., & Flaws, J. A. (2011) · doi:10.1002/9781118140574.ch31 · Cited by 18 · see citing works
Seok, J., Jun, S., Cho, J., Park, S., Lee, J. O., & Kim, G. J. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30330 · Cited by 17 · see citing works
Oxygen governs Galβ1–3GalNAc epitope in human placenta
Ermini, L., Bhattacharjee, J., Spagnoletti, A., Bechi, N., Aldi, S., Ferretti, C., Bianchi, L., Bini, L., Rosati, F., Paulesu, L. R., et al. (2013) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00407.2012 · Cited by 17 · see citing works
Self-citationMcCracken, S. A., Seeho, S. K. M., Carrodus, T., Park, J. H., Woodland, N., Gallery, E. D. M., Morris, J. M., & Ashton, A. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052772 · Cited by 16 · see citing works
Halder, D., Park, J. H., Choi, M., Chai, J. C., Lee, Y. S., Mandal, C., Jung, K. H., & Chai, Y. G. (2013) · Journal of Applied Toxicology · doi:10.1002/jat.2832 · Cited by 16 · see citing works
Oxygen regulates human cytotrophoblast migration by controlling chemokine and receptor expression
Schanz, A., Red‐Horse, K., Hess, A. P., Baston-Büst, D. M., Heiß, C., & Krüssel, J.-S. (2014) · Placenta · doi:10.1016/j.placenta.2014.09.012 · Cited by 16 · see citing works
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
Vornic, I., Căprariu, R., Novacescu, D., Barb, A. C., Buciu, V. B., Băloi, A., Szekely, D., Suciu, C. S., Dumitru, C., Pătrașcu, R., et al. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26199483 · Cited by 15 · see citing works
Alahari, S., Garcia, J., Post, M., & Caniggia, I. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.07.016 · Cited by 14 · see citing works
Self-citationSeasonally variant gene expression in full‐term human placenta
Clarkson-Townsend, D. A., Kennedy, E. M., Everson, T. M., Deyssenroth, M. A., Burt, A., Hao, K., Chen, J., Pardue, M. T., & Marsit, C. J. (2020) · The FASEB Journal · doi:10.1096/fj.202000291r · Cited by 14 · see citing works
Dysregulation of hypoxia-inducible factor-1α (Hif1α) expression in the Hmox1-deficient placenta
Zhao, H. F., Narasimhan, P., Kalish, F. S., Wong, R. J., & Stevenson, D. K. (2020) · Placenta · doi:10.1016/j.placenta.2020.07.015 · Cited by 14 · see citing works
Dakouane‐Giudicelli, M., Alfaidy, N., Bayle, P., de Nonneville, A. T., Studer, V., Rozenberg, P., & de Mazancourt, P. (2011) · The International Journal of Developmental Biology · doi:10.1387/ijdb.103276md · Cited by 14 · see citing works
Trophoblast adaptation to hypoxia: balance and dysfunction
Li, Q., Wei, X., Zhang, Y., Zeng, W., & Lin, Y. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02531-2 · Cited by 15 · see citing works
Hu, R., Wang, Q., Jia, Y., Zhang, Y., Wu, B., Tian, S., Wang, Y., Wang, Y., & Ma, W. (2021) · Tissue and Cell · doi:10.1016/j.tice.2021.101616 · Cited by 13 · see citing works
Wang, S., Wang, X., Weng, Z., Zhang, S., Ning, H., & Li, B. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5067 · Cited by 13 · see citing works
Tang, Z., Zhang, Z., Tang, Y., Qi, L., Yang, F., & Wang, Z. (2017) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2017.5328 · Cited by 13 · see citing works
Lehtoranta, L., Vuolteenaho, O. J., Laine, J., Polari, L., Ekholm, E. M. K., & Rasanen, J. P. (2016) · Placenta · doi:10.1016/j.placenta.2016.06.002 · Cited by 12 · see citing works
Alahari, S., Farrell, A., Ermini, L., Park, C., Sallais, J., Roberts, S., Gillmore, T., Litvack, M. L., Post, M., & Caniggia, I. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.652607 · Cited by 12 · see citing works
Self-citationDepoix, C. L., Flabat, O., Debiève, F., & Hubinont, C. (2016) · Reproductive Biology · doi:10.1016/j.repbio.2016.05.001 · Cited by 11 · see citing works
Oxygen and tissue culture affect placental gene expression
Brew, O., & Sullivan, M. H. F. (2017) · Placenta · doi:10.1016/j.placenta.2017.04.024 · Cited by 11 · see citing works
Yue, T., Guo, Y., Qi, X., Zheng, W., Zhang, H., Wang, B., Liu, K., Zhou, B., Zeng, X., Ouzhuluobu, et al. (2023) · eLife · doi:10.7554/elife.89004 · Cited by 13 · see citing works
Factor inhibiting HIF1-A novel target of SUMOylation in the human placenta
Sallais, J., Alahari, S., Tagliaferro, A., Bhattacharjee, J., Post, M., & Caniggia, I. (2017) · Oncotarget · doi:10.18632/oncotarget.23113 · Cited by 10 · see citing works
Self-citationMa, R., Liu, J., Ma, X., & Yang, J. H. (2025) · Genes · doi:10.3390/genes16030316 · Cited by 8 · see citing works
VCNet: vector-based gene co-expression network construction and its application to RNA-seq data
Wang, Z., Fang, H., Tang, N. L. S., & Deng, M. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx131 · Cited by 8 · see citing works
Evaluation of circ_100219 and miR-135b in serum and exosomes of healthy pregnant women
Montagnana, M., Benati, M., Tagetti, A., Raffaelli, R., Danese, E., Zatti, N., Marcon, D., Branz, L., Micheli, C., Franchi, M. P., et al. (2019) · The Journal of Maternal-Fetal & Neonatal Medicine · doi:10.1080/14767058.2019.1689556 · Cited by 8 · see citing works
REDD1 Expression in Placenta During Human Gestation
Hu, Y. Y., Liu, J. C., Xing, A., You, Y., & Wang, X. D. (2012) · Reproductive Sciences · doi:10.1177/1933719112440054 · Cited by 7 · see citing works
Cordeiro, J. M. D. A., Santos, L. C., Santos, B. R., Santos, E. O., Nascimento, A. E. D. J., de Freitas, G. J. C., Singulani, J. D. L., Santos, D. A., de Lavor, M. S. L., & Silva, J. F. (2023) · Reproduction Fertility and Development · doi:10.1071/rd22123 · Cited by 5 · see citing works
Yue, T., Guo, Y., Qi, X., Zheng, W., Zhang, H., Wang, B., Liu, K., Zhou, B., Zeng, X., Ouzhuluobu, et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.05.24.542081 · Cited by 5 · see citing works
Yue, T., Guo, Y., Qi, X., Zheng, W., Zhang, H., Wang, B., Liu, K., Zhou, B., Zeng, X., Ouzhuluobu, et al. (2023) · eLife · doi:10.7554/elife.89004.2 · Cited by 5 · see citing works
Gene networks for total number born in pigs across divergent environments
Verardo, L. L., Lopes, M. S., Mathur, P. K., Madsen, O., Silva, F. F. E., Groenen, M. A. M., Knol, E. F., Lopes, P. S., & Guimarães, S. E. F. (2017) · Mammalian Genome · doi:10.1007/s00335-017-9696-5 · Cited by 4 · see citing works
Glycolysis in polycystic ovary syndrome: pathogenesis and treatment
Xing, L., Shi, M., Wang, Z., Gao, H., Li, D., Guo, R. J., Zhou, X., Chen, Y., Xu, J., Liang, Z., et al. (2025) · Journal of Ovarian Research · doi:10.1186/s13048-025-01908-8 · Cited by 3 · see citing works
Self-citationLiang, Z., Hu, S., Dong, Y., Miao, L., Zhu, W., Feng, B., Fu, J., Luo, M., Wang, L., & Dong, Z. (2024) · Fish Physiology and Biochemistry · doi:10.1007/s10695-024-01356-z · Cited by 3 · see citing works
Özçakır, H. T., Turan, M. A., Şimşek, F. Ş., Atay, C., Vatansever, S., & Özbilgin, K. (2015) · Clinical and Experimental Obstetrics & Gynecology · doi:10.12891/ceog1774.2015 · Cited by 3 · see citing works
Yue, T., Guo, Y., Qi, X., Zheng, W., Zhang, H., Wang, B., Liu, K., Zhou, B., Zeng, X., Ouzhuluobu, et al. (2024) · eLife · doi:10.7554/elife.89004.3 · Cited by 3 · see citing works
Zarychta, J., Kowalczyk, A., Słowik, K., Przywara, D., Petniak, A., Kondracka, A., Wójtowicz‐Marzec, M., Słyk-Gulewska, P., Kwaśniewska, A., Kocki, J., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252011042 · Cited by 2 · see citing works
Zou, Y., Ai, H., Miao, G., Hu, Y., Liu, H., Xia, B., Xin, T., & Zou, Z. (2025) · Pest Management Science · doi:10.1002/ps.70231 · Cited by 2 · see citing works
Role of SOX9 and Hif-1α expression in placentas of patients with HELLP
Akalın, S. A., Öcal, E., & Devecí, E. (2023) · Acta Cirúrgica Brasileira · doi:10.1590/acb388023 · Cited by 2 · see citing works
- Authors
- Ietta, F., Wu, Y., Winter, J., Xu, J., Wang, J., Post, M., & Caniggia, I.
- Affiliations
- Mount Sinai Hospital (CA)
- University of Toronto (CA)
- Corresponding author
- Caniggia, Isabella
- Venue
- Biology of Reproduction
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-07-01
- Volume
- 75
- Issue
- 1
- Pages
- 112-121
- ISSN
- 0006-3363 (ISSN-L)
- 1529-7268
- OpenAlex
- W2097321304
- Cited by
- 127
- References
- 41
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 6 · 2023: 7 · 2022: 3 · 2021: 7 · 2020: 6 · 2019: 4 · 2018: 6 · 2017: 12 · 2016: 7 · 2015: 6 · 2014: 9 · 2013: 6 · 2012: 7
- FWCI
- 5.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biology of Reproduction (publishedVersion)
- PubMed (publishedVersion)
- BioOne Complete (BioOne) (submittedVersion)
- Use Siena air (University of Siena) (submittedVersion)
- Funders
- Canada Research Chairs
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- HIF1A, hypoxia, von Hippel-Lindau protein, prolyl hydroxylase, CUL2, ubiquitination, oxygen partial pressure, cytotrophoblast, syncytiotrophoblast, transforming growth factor-beta3
- MeSH terms
- Hypoxia, Female, Humans, Nuclear Proteins, Organ Culture Techniques, Oxygen, Placenta, Placentation, Pregnancy, Procollagen-Proline Dioxygenase, Transfection, Trophoblasts, Transcriptional Activation, Transforming Growth Factor beta, Dioxygenases, Aryl Hydrocarbon Receptor Nuclear Translocator, Von Hippel-Lindau Tumor Suppressor Protein, Hypoxia-Inducible Factor 1, alpha Subunit, Transforming Growth Factor beta3, Hypoxia-Inducible Factor-Proline Dioxygenases
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