Energy status and HIF signalling in chorionic villi show no evidence of hypoxic stress during human early placental development
Open accessAbstract
Early human placental and embryonic development occurs in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile in the first, second and third trimesters to determine whether the energy demands are adequately met in the first trimester. We investigated whether hypoxia-inducible factors, HIF-1α and/or HIF-2α, might regulate transcription during the first trimester. First and second trimester tissue was collected using a chorionic villus sampling-like (CVS) technique. Part of each villus sample was frozen immediately and the remainder cultured under 2 or 21% O2 ± 1 mM H2O2, and ±the p38 MAPK pathway inhibitor, PD169316. Levels of HIF-1α were assessed by western blotting and VEGFA, PlGF and GLUT3 transcripts were quantified by RT-PCR. Term samples were collected from normal elective Caesarean deliveries. There were no significant differences in concentrations of ADP, NAD(+), lactate, and glucose, and in the ATP/ADP ratio, across gestational age. Neither HIF-1α nor HIF-2α could be detected in time-zero CVS samples. However, culture under any condition (2 or 21% O2 ± 1 mM H2O2) increased HIF-1α and HIF-2α. HIF-1α and HIF-2α were additionally detected in specimens retrieved after curettage. HIF-1α stabilization was accompanied by significant increases in VEGFA and GLUT3 and a decrease in PlGF mRNAs. These effects were suppressed by PD169316. In conclusion, our data suggest that first trimester placental tissues are not energetically compromised, and that HIF-1α is unlikely to play an appreciable role in regulating transcriptional activity under steady-state conditions in vivo. However, the pathway may be activated by stress conditions.
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HIF-1 and HIF-2 can be stabilized in chorionic villus sampling samples by stress and activate downstream targets, including VEGF.
“Equally, HIF-1 and HIF-2 can be stabilized in CVS samples by stress and activate downstream targets, including VEGF (112).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [112]
Stress induced on tissues during collection, especially by curettage, is a potential confounder in studies of placental HIF expression.
“Another potential confounder is stress induced on the tissues during collection, especially when this is performed by curettage when they are inevitably mixed with maternal blood (112).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [112]
The ATP/ADP ratio is the same during the first and early second trimesters and at term.
“This is supported by the observation that the ATP/ADP ratio is the same during the first and early second trimesters and at term (112).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [112]
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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 · cited 3× · see citing works
“PHD hydroxylation of HIF-1a and HIF-2a under normoxia leads to HIF binding of VHL and subsequent polyubiquitination and proteosomal degradation (Maxwell et al., 1999; Bruick and McKnight, 2001; Ivan et al., 2001).”
BackgroundActivation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1
Forsythe, J. A., Jiang, B.-H., Iyer, N. V., Agani, F., Leung, S. W., Koos, R. D., & Semenza, G. L. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.9.4604 · Cited by 3,981 · 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
Regulation of Mammalian O <sub>2</sub> Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · see citing works
Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1.
Semenza, G., Roth, P. H., Fang, H. M., & Wang, G. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31580-6 · Cited by 1,892 · 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
Self-citationSemenza, G. L. (2001) · Cell · doi:10.1016/s0092-8674(01)00518-9 · Cited by 935 · see citing works
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 oxidative stress: from miscarriage to preeclampsia
Burton, G. J., & Jauniaux, E. (2004) · Journal of the Society for Gynecologic Investigation · doi:10.1016/j.jsgi.2004.03.003 · Cited by 673 · see citing works
Self-citationCaniggia, 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
HIF-1 as a target for drug development
Giaccia, A., Siim, B. G., & Johnson, R. S. (2003) · Nature Reviews Drug Discovery · doi:10.1038/nrd1199 · Cited by 631 · see citing works
Burton, G. J., Watson, A. L., Hempstock, J., Skepper, J. N., & Jauniaux, E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.6.8563 · Cited by 567 · see citing works
Self-citationJauniaux, E., Hempstock, J., Greenwold, N., & Burton, G. J. (2003) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63803-5 · Cited by 511 · see citing works
Self-citationBurton, 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
Self-citationPlacental apoptosis in normal human pregnancy
SMITH, S. C. H., Baker, P. N., & SYMONDS, E. M. (1997) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(97)70438-1 · Cited by 400 · see citing works
Histological study of the materno-embryonic interface in spontaneous abortion
Hustin, J., Jauniaux, E. R. M., & Schaaps, J. P. (1990) · Placenta · doi:10.1016/s0143-4004(05)80193-6 · Cited by 299 · see citing works
Self-citationOxidative Stress, Gene Expression, and Protein Changes Induced in the Human Placenta during Labor
Cindrová‐Davies, T., Yung, H. W., Johns, J., Spasić-Bošković, O., Korolchuk, S., Jauniaux, E. R. M., Burton, G. J., & Jones, D. S. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.070528 · Cited by 296 · see citing works
Self-citationBeyond 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
Hempstock, J., Cindrová‐Davies, T., Jauniaux, E. R. M., & Burton, G. J. (2004) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-2-58 · Cited by 229 · see citing works
Self-citationTrophoblastic Oxidative Stress and the Release of Cell-Free Feto-Placental DNA
Tjoa, M. L., Cindrová‐Davies, T., Spasić-Bošković, O., Bianchi, D. W., & Burton, G. J. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060161 · Cited by 225 · see citing works
Self-citationThe HIF family member EPAS1/HIF-2α is required for normal hematopoiesis in mice
Scortegagna, M., Morris, M. A., Oktay, Y., Bennett, M., & Garcia, J. A. (2003) · Blood · doi:10.1182/blood-2003-02-0448 · Cited by 203 · see citing works
Pugh, C. W., & Ratcliffe, P. J. (2002) · Seminars in Cancer Biology · doi:10.1016/s1044-579x(02)00103-7 · Cited by 202 · see citing works
Cindrová‐Davies, T., Spasić-Bošković, O., Jauniaux, E. R. M., Jones, D. S., & Burton, G. J. (2007) · American Journal Of Pathology · doi:10.2353/ajpath.2007.061035 · Cited by 190 · see citing works
Self-citationJung, Y., Isaacs, J. S., Lee, S., Trepel, J. B., Liu, Z.-G., & Neckers, L. (2003) · Biochemical Journal · doi:10.1042/bj20021279 · Cited by 190 · see citing works
Redox regulation of the hypoxia-inducible factor
Pouysségur, J., & Mechta-Grigoriou, F. (2006) · Biological Chemistry · doi:10.1515/bc.2006.167 · Cited by 186 · see citing works
Rajakumar, A., & Conrad, K. P. (2000) · Biology of Reproduction · doi:10.1095/biolreprod63.2.559 · Cited by 177 · see citing works
Functional regulation of HIF‐1α under normoxia—is there more than post‐translational regulation?
Kuschel, A., Simon, P. D., & Tug, S. (2011) · Journal of Cellular Physiology · doi:10.1002/jcp.22798 · Cited by 170 · see citing works
Jauniaux, E., Hempstock, J., Teng, C., Battaglia, F. C., & Burton, G. J. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-1513 · Cited by 153 · see citing works
Self-citationCindrová‐Davies, T. (2009) · Placenta · doi:10.1016/j.placenta.2008.11.020 · Cited by 145 · see citing works
Hypoxia Tolerance in Animals: Biology and Application
Gorr, T. A., Wichmann, D., Hu, J., Hermes‐Lima, M., Welker, A. F., Terwilliger, N., Wren, J. F., Viney, M., Morris, S., Nilsson, G. E., et al. (2010) · Physiological and Biochemical Zoology · doi:10.1086/648581 · Cited by 134 · 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
Serkova, N. J., Rose, J. C., Epperson, L. E., Carey, H. V., & Martin, S. L. (2007) · Physiological Genomics · doi:10.1152/physiolgenomics.00028.2007 · Cited by 124 · see citing works
Human placental metabolic adaptation to chronic hypoxia, high altitude: hypoxic preconditioning
Tissot van Patot, M. C., Murray, A. J., Beckey, V., Cindrova-Davies, T., Johns, J., Zwerdlinger, L., Jauniaux, E., Burton, G. J., & Serkova, N. J. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00383.2009 · Cited by 107 · see citing works
Self-citationMenon, D. K., Sargentoni, J., Taylor-Robinson, S. D., Bell, J. D., Cox, I. J., Bryant, D. J., Coults, G. A., Rolles, K., Burroughs, A. K., & Margan, M. Y. (1995) · Hepatology · doi:10.1002/hep.1840210224 · Cited by 105 · 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
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
Ishihara, N., Matsuo, H., Murakoshi, H., Laoag‐Fernandez, J. B., Samoto, T., & Maruo, T. (2000) · Endocrine Journal · doi:10.1507/endocrj.47.317 · Cited by 63 · see citing works
Chen, R. (2002) · Human Reproduction · doi:10.1093/humrep/17.2.463 · Cited by 50 · see citing works
Serkova, N. J., Bendrick‐Peart, J., Alexander, B., & van Patot, M. C. T. (2003) · Placenta · doi:10.1053/plac.2002.0908 · Cited by 37 · see citing works
Sohlberg, S., Wikström, A.-K., Olovsson, M. H., Lindgren, P., Axelssön, O., Mulic‐Lutvica, A., Weis, J., & Wikström, J. (2014) · Placenta · doi:10.1016/j.placenta.2014.02.005 · Cited by 25 · see citing works
Regulation of Creatine Kinase Isoenzymes in Human Placenta During Early, Mid-, and Late Gestation
Thomure, M. F., GAST, M., SRIVASTAVA, N., & Payne, R. M. (1996) · Journal of the Society for Gynecologic Investigation · doi:10.1016/s1071-5576(96)00043-3 · Cited by 18 · see citing works
Flagged first, then by citations
2 of the 45 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Pre-eclampsia: pathogenesis, novel diagnostics and therapies
Phipps, E. A., Thadhani, R., Benzing, T. R., & Karumanchi, S. A. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0119-6 · Cited by 1,255 · see citing works
Pathophysiology of placental-derived fetal growth restriction
Burton, G. J., & Jauniaux, E. (2018) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2017.11.577 · Cited by 1,070 · see citing works
Self-citationPlacental 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
Self-citationOxidative stress: Normal pregnancy versus preeclampsia
Chiarello, D. I., Abad, C., Rojas, D., Toledo, F., Vázquez, C. M., Mate, A., Sobrevía, L., & Marı́n, R. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.12.005 · Cited by 394 · see citing works
Human placental development and function
Cindrová‐Davies, T., & Sferruzzi-Perri, A. N. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.03.039 · Cited by 280 · see citing works
HYPOXIA AND REPRODUCTIVE HEALTH: Oxygen and development of the human placenta
Burton, G. J., Cindrová‐Davies, T., Yung, H. W., & Jauniaux, E. R. M. (2020) · Reproduction · doi:10.1530/rep-20-0153 · Cited by 188 · see citing works
Self-citationOxidative stress and mitochondrial dysfunction in early-onset and late-onset preeclampsia
Marı́n, R., Chiarello, D. I., Abad, C., Rojas, D., Toledo, F., & Sobrevía, L. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2020.165961 · Cited by 190 · see citing works
Aye, I. L. M. H., Aiken, C., Jones, D. S., & Smith, G. C. S. (2020) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2020.11.005 · Cited by 155 · see citing works
Development of the Human Placenta and Fetal Heart: Synergic or Independent?
Burton, G. J., & Jauniaux, E. R. M. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.00373 · Cited by 152 · see citing works
Self-citationColson, A., Sonveaux, P., Debiève, F., & Sferruzzi-Perri, A. N. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmaa053 · Cited by 145 · see citing works
Cindrova-Davies, T., Fogarty, N. M. E., Jones, C. J. P., Kingdom, J., & Burton, G. J. (2018) · Placenta · doi:10.1016/j.placenta.2018.06.307 · Cited by 127 · see citing works
Self-citationDecreased ATP production and myocardial contractile reserve in metabolic heart disease
Luptak, I., Sverdlov, A. L., Panagia, M., Qin, F., Pimentel, D. R., Croteau, D., Siwik, D. A., Ingwall, J. S., Bachschmid, M. M., Balschi, J. A., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.01.017 · Cited by 103 · see citing works
Oxygen and placental development; parallels and differences with tumour biology
Burton, G. J., Jauniaux, E. R. M., & Murray, A. J. (2017) · Placenta · doi:10.1016/j.placenta.2017.01.130 · Cited by 79 · see citing works
Self-citationPreliminary metabolomics analysis of placenta in maternal obesity
Fattuoni, C., Mandò, C., Palmas, F., Anelli, G. M., Novielli, C., Laudicina, E. P., Savasi, V. M., Barberini, L., Dessì, A., Pintus, R., et al. (2017) · Placenta · doi:10.1016/j.placenta.2017.11.014 · Cited by 76 · see citing works
The human placenta: new perspectives on its formation and function during early pregnancy
Burton, G. J., & Jauniaux, E. R. M. (2023) · Proceedings of the Royal Society B Biological Sciences · doi:10.1098/rspb.2023.0191 · Cited by 76 · see citing works
Self-citationHighet, 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
Review: Histotrophic nutrition and the placental-endometrial dialogue during human early pregnancy
Burton, G. J., Cindrová‐Davies, T., & Turco, M. Y. (2020) · Placenta · doi:10.1016/j.placenta.2020.02.008 · Cited by 68 · see citing works
Self-citationHypoxia and the endometrium: An indispensable role for HIF-1α as therapeutic strategies
Dai, W., Guo, R., Na, X., Jiang, S., Liang, J., Guo, C., Fang, Y., Na, Z., & Li, D. (2024) · Redox Biology · doi:10.1016/j.redox.2024.103205 · Cited by 62 · see citing works
Sun, Y., Wang, C., Sun, X., & Guo, M. (2019) · Journal of Food Science · doi:10.1111/1750-3841.14428 · Cited by 59 · see citing works
Le rôle du stress oxydant dans les pathologies placentaires de la grossesse
Jauniaux, E. R. M., & Burton, G. J. (2016) · Journal de gynécologie, obstétrique et biologie de la reproduction. Supplément/Journal de gynécologie obstétrique et biologie de la reproduction · doi:10.1016/j.jgyn.2016.02.012 · Cited by 54 · see citing works
Self-citationDiabesity-associated oxidative and inflammatory stress signalling in the early human placenta
Hoch, D., Gauster, M., Mouzon, S. H., & Desoyé, G. (2018) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.11.002 · Cited by 53 · 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
Kurlak, L. O., Mistry, H. D., Cindrova‐Davies, T., Burton, G. J., & Pipkin, F. B. (2015) · The Journal of Physiology · doi:10.1113/jp271045 · Cited by 46 · see citing works
Self-citationRobillard, P., Dekker, G., Iacobelli, S., & Chaouat, G. (2015) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2015.07.001 · Cited by 43 · see citing works
Prater, M., Hamilton, R. S., Yung, H. W., Sharkey, A., Robson, P., Hamid, N. E. A., Jauniaux, E. R. M., Jones, D. S., Burton, G. J., & Cindrová‐Davies, T. (2021) · Biology Open · doi:10.1242/bio.058222 · Cited by 42 · see citing works
Self-citationThe human placenta and its role in reproductive outcomes revisited
Aye, I. L. M. H., Tong, S., Jones, D. S., & Smith, G. C. S. (2025) · Physiological Reviews · doi:10.1152/physrev.00039.2024 · Cited by 45 · see citing works
Pan, H., Ding, H., Fang, M., Yu, B., Cheng, Y., Tan, Y., Fu, Q., Lu, B., Cai, H., Jin, X., et al. (2017) · Placenta · doi:10.1016/j.placenta.2017.11.001 · Cited by 40 · see citing works
Fetomaternal Expression of Glucose Transporters (GLUTs)—Biochemical, Cellular and Clinical Aspects
Sibiak, R., Ożegowska, K., Wender-Ożegowska, E., Gutaj, P., Mozdziak, P. E., & Kempisty, B. (2022) · Nutrients · doi:10.3390/nu14102025 · Cited by 40 · see citing works
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
Hu, X., & Zhang, L. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.07.011 · Cited by 36 · see citing works
Biomarkers of oxidative stress and reproductive complications
Marı́n, R., Abad, C., Rojas, D., Chiarello, D. I., & Teppa-Garrán, A. (2023) · Advances in clinical chemistry · doi:10.1016/bs.acc.2022.11.004 · Cited by 36 · see citing works
Systematic review of p38 mitogen‐activated kinase and its functional role in reproductive tissues
Sheller‐Miller, S., Richardson, L., Martin, L., Jin, J., & Menon, R. (2018) · American Journal of Reproductive Immunology · doi:10.1111/aji.13047 · Cited by 29 · see citing works
Placentation in the Human and Higher Primates
Burton, G. J., & Jauniaux, E. R. M. (2021) · Advances in anatomy, embryology and cell biology · doi:10.1007/978-3-030-77360-1_11 · Cited by 28 · see citing works
Self-citationBanadakoppa, M., Balakrishnan, M. P., & Yallampalli, C. (2018) · American Journal of Reproductive Immunology · doi:10.1111/aji.13033 · Cited by 26 · see citing works
Hahn, S., Lapaire, O., & Than, N. G. (2015) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2015.1025757 · Cited by 23 · see citing works
SARS- CoV-2 infection and oxidative stress in early-onset preeclampsia
Marı́n, R., Pujol, F. H., Rojas, D., & Sobrevía, L. (2021) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2021.166321 · Cited by 20 · see citing works
Li, L., & Baek, K. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26052263 · Cited by 18 · see citing works
Jakovljevic, T. S., Kontić‐Vučinić, O., Nikolić, N., Čarkić, J., Stamenković, J., Soldatović, I., & Milašin, J. (2021) · Reproductive Sciences · doi:10.1007/s43032-021-00632-0 · Cited by 18 · see citing works
Zhao, H., Wu, L., Wang, Y., Zhou, J., Li, R., Zhou, J., Wang, Z., & Xu, C. (2017) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2016.12.014 · Cited by 15 · see citing works
Metabolomic Investigation of β-Thalassemia in Chorionic Villi Samples
Monni, G., Murgia, F., Corda, V., Peddes, C., Iuculano, A., Tronci, L., Balsamo, A., & Atzori, L. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8060798 · Cited by 14 · see citing works
Elkin, E. R., Bridges, D., Harris, S. M., & Loch-Caruso, R. K. (2020) · Chemical Research in Toxicology · doi:10.1021/acs.chemrestox.9b00356 · Cited by 14 · see citing works
Hufnagel, A., Grant, I. D., & Aiken, C. (2022) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2022.03.041 · Cited by 13 · see citing works
Abid, N., Embola, J., Tryfonos, Z., Bercher, J., Ashton, S. V., Khalil, A. A., Thilaganathan, B., Cartwright, J. E., & Whitley, G. S. J. (2020) · The FASEB Journal · doi:10.1096/fj.201902426r · Cited by 12 · see citing works
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
Depoix, 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
Parental ancestry and risk of early pregnancy loss at high altitude
Grant, I. D., Soria, R., Julian, C. G., Vargas, E., MOORE, L. G., Aiken, C., & Giussani, D. A. (2020) · The FASEB Journal · doi:10.1096/fj.202001257r · Cited by 11 · see citing works
Liu, J., Zhao, M., Zhang, S., & Shi, Y. (2025) · Journal of Molecular Histology · doi:10.1007/s10735-025-10579-0 · Cited by 10 · see citing works
Metabolic fingerprinting of chorionic villous samples in normal pregnancy and chromosomal disorders
Murgia, F., Iuculano, A., Peddes, C., Santoru, M. L., Tronci, L., Deiana, M., Atzori, L., & Monni, G. (2019) · Prenatal Diagnosis · doi:10.1002/pd.5461 · Cited by 9 · see citing works
Hoch, D., Majali‐Martinez, A., Bandres‐Meriz, J., Bachbauer, M., Pöchlauer, C., Kaudela, T., Bankoglu, E. E., Stopper, H., Glasner, A., Mouzon, S. H., et al. (2024) · Molecular Human Reproduction · doi:10.1093/molehr/gaae027 · Cited by 7 · see citing works
Gan, B., Wu, X., Lü, L., Li, X., & Li, J. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.771738 · Cited by 7 · see citing works
THE ROLE OF FREE-RADICAL OXIDATION PROCESSES IN THE PATHOGENESIS OF EARLY MISCARRIAGE
Геннадьевна, Т. О., Dikareva, L., & Tepliy, D. L. (2023) · ASTRAKHAN MEDICAL JOURNAL · doi:10.29039/1992-6499-2023-1-27-38 · Cited by 5 · see citing works
Zhang, P. (2020) · Reproductive Medicine · doi:10.3390/reprodmed1020006 · Cited by 5 · see citing works
Hypoxia-inducible factors (HIFs) in early pregnancy: implications for miscarriage
Lai, Y., Fu, Z., Gao, Y., Ma, N., & Li, L. (2024) · Biology of Reproduction · doi:10.1093/biolre/ioae139 · Cited by 4 · see citing works
Early Development of the Human Placenta
Burton, G. J., & Jauniaux, E. R. M. (2021) · Springer eBooks · doi:10.1007/978-3-030-84725-8_5 · Cited by 4 · see citing works
Self-citationJones, D. S., Jauniaux, E. R. M., & Burton, G. J. (2021) · Springer eBooks · doi:10.1007/978-3-030-84725-8_9 · Cited by 4 · see citing works
Self-citationBilginer, C., & Cetin, A. (2026) · Frontiers in Medicine · doi:10.3389/fmed.2026.1874122 · Cited by 2 · see citing works
Oxidative Stress in Preeclampsia and Preterm Newborn
Abad, C., Chiarello, D. I., Rojas, D., Beretta, V., Perrone, S., & Marı́n, R. (2024) · Springer eBooks · doi:10.1007/978-3-031-69962-7_10 · Cited by 1 · see citing works
Placental causes of fetal growth restriction and treatment methods
Александровна, Б. А., Pachuliia, O. V., Bespalova, O. N., & Kogan, I. Y. (2024) · Психофармакология и биологическая наркология · doi:10.17816/phbn637465 · Cited by 1 · see citing works
Risks and mechanisms of preeclampsia
Рудаева, Е. В., Мозес, В. Г., Кашталап, В. В., & Елгина, С. И. (2025) · Russian Military Medical Academy Reports · doi:10.17816/rmmar643152 · Cited by 1 · see citing works
Some Aspects of the Physiology of the Placenta
Longo, L. D. (2018) · Springer eBooks · doi:10.1007/978-1-4939-7483-2_8 · Cited by 1 · see citing works
Gong, H.-Z., Guan, J., Pan, Y.-Z., Ding, H., Shi, A., & Gu, N. (2025) · PLoS ONE · doi:10.1371/journal.pone.0314544 · Cited by 1 · see citing works
RetractedSome Aspects of the Physiology of the Placenta
Longo, L. D. (2013) · Springer eBooks · doi:10.1007/978-1-4614-7921-5_8
Noviyana, A., Nooryanto, M., & Andarini, S. (2017) · Clinical Nutrition Experimental · doi:10.1016/j.yclnex.2017.03.001
Placentation and Placental Function in Normal and Preeclamptic Pregnancies
Burton, G. J., Cindrová‐Davies, T., Yung, H. W., & Taylor, R. N. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-818417-2.00004-x
Self-citationBurton, G. J., & Jauniaux, E. R. M. (2017) · Cambridge University Press eBooks · doi:10.1017/9781139976787.004
Self-citationMOLECULAR PATHWAYS THAT PLAY A ROLE IN THE PREECLAMPSIA PATHOPHYSIOLOGY
Fındık, D. G., & Take, G. (2023) · Kocatepe tıp dergisi. · doi:10.18229/kocatepetip.988858
Mezhevitinova, E. A., Iurova, M. V., Abakarova, P. R., & Kepsha, M. A. (2024) · Meditsinskiy sovet = Medical Council · doi:10.21518/ms2023-457
Liu, J., Su, Z., Ding, J., & Fang, Y. (2025) · Arabian Journal of Chemistry · doi:10.25259/ajc_459_2025
Stein, F. H., Le, N. H., & Elkin, E. R. (2025) · Toxicology Letters · doi:10.1016/j.toxlet.2025.111773
Shi, M.-L., Liu, G.-H., & Bao, F.-X. (2026) · Advanced ultrasound in diagnosis and therapy · doi:10.26599/audt.2026.250064
Poinsignon, L., Chissey, A., Colombel, J., Lefrère, B., Izabelle, C., Bernard, L., Beaudeux, J., Fournier, T., Ferecatu, I., Hernandez, I., et al. (2026) · iScience · doi:10.1016/j.isci.2026.115674
Liu, S., Zhang, Y. W., Zhao, C., Luo, Y., Wang, M., Zhang, R., Chen, C., Fei, J., Liu, H., Jiang, Y., et al. (2026) · Photoacoustics · doi:10.1016/j.pacs.2026.100848
Hoch, D., Majali‐Martinez, A., Algaba‐Chueca, F., Tokic, S., & Desoyé, G. (2026) · Biomolecules · doi:10.3390/biom16071033
- Authors
- Cindrova-Davies, T., van Patot, M. T., Gardner, L., Jauniaux, E., Burton, G. J., & Charnock-Jones, D. S.
- Affiliations
- University of Cambridge (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Burton, G. J.
- Venue
- MHR: Basic science of reproductive medicine
- Publisher
- Oxford University Press (OUP)
- Published
- 2014-11-11
- Volume
- 21
- Issue
- 3
- Pages
- 296-308
- ISSN
- 1360-9947 (ISSN-L)
- 1460-2407
- PMC
- PMC4339857
- OpenAlex
- W2160782334
- Cited by
- 74
- References
- 45
- Citations by year
- 2026: 5 · 2025: 7 · 2024: 6 · 2023: 5 · 2022: 5 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 9 · 2017: 7 · 2016: 3 · 2015: 5 · 2013: 1
- FWCI
- 5.32
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Molecular Human Reproduction (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (084804, 084804/2/08/Z)
- 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
- placental development, hypoxia, HIF-1α, HIF-2α, chorionic villi, placental metabolomics, energy metabolism, VEGF-A, placental growth factor, GLUT3, p38 MAPK, PD169316, low oxygen environment, first trimester, oxidative stress
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Adenosine Diphosphate, Adenosine Triphosphate, Adult, Chorionic Villi, Energy Metabolism, Female, Humans, Hydrogen Peroxide, Imidazoles, Membrane Proteins, Oxygen, Placentation, Pregnancy, Pregnancy Trimesters, Transcription, Genetic, Signal Transduction, Cell Hypoxia, Gene Expression Regulation, Developmental, Vascular Endothelial Growth Factor A, p38 Mitogen-Activated Protein Kinases, Glucose Transporter Type 3, Basic Helix-Loop-Helix Transcription Factors, Basic Helix-Loop-Helix Proteins, Hypoxia-Inducible Factor 1, alpha Subunit, Primary Cell Culture
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