Oxygenation of the placental–fetal unit in humans

Schneider, Henning

doi:10.1016/j.resp.2011.05.009

Cited by 84Pregnancy and preeclampsia studiesReproductive System and PregnancyBirth, Development, and Health

Oxygenation of the placental–fetal unit in humans

Schneider, Henning·2011·Respiratory Physiology & Neurobiology

DOI 10.1016/j.resp.2011.05.009

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Abstract

This review focuses on the role of oxygen and the changes in oxygen levels in the different trimesters of pregnancy in the human placenta. In the first trimester, the physiological conversion of the spiral arteries restricts maternal blood flow into the intervillous space creating a low oxygen environment for the trophoblast and the embryo. In the second trimester, progressive conversion of the spiral arteries allows unhindered entrance of maternal blood into the intervillous space. In early pregnancy, pathology of spiral artery conversion may promote premature flow of maternal blood resulting in miscarriage. In more advanced pregnancy, incomplete conversion of spiral arteries impairs maternal blood flow to the placenta, causing chronic hypoxia and growth restriction of the fetus. Chronically reduced maternal supply of oxygen to the placental-fetal unit may be partially balanced by metabolic reprogramming of the placenta. Acute impairment of oxygenation in the perinatal period and its effect on the placental-fetal unit will also be discussed.

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Hypoxia is one of the most common complications of human pregnancy, occurring in 9-10% of pregnancies at sea level and all pregnancies at high altitude.
“Hypoxia is one of the most common complications of human pregnancy, occurring in 9-10% of pregnancies at sea level and all pregnancies at high altitude (484, 600).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [484]

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Arterial blood flow into the human intervillous space
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Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation
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Trophoblast Viability in Perfused Term Placental Tissue and Explant Cultures Limited to 7–24 hours
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Metabolic adaptation to hypoxia: cost and benefit of being small
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Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants
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Nucleotide, nucleoside and purine base concentrations in human placentae
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Mechanical and metabolic viability of a placental perfusion system in vitro under oxygenated and anoxic conditions
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Hypoxic preconditioning produces differential expression of hypoxia-inducible factor-1α (HIF-1α) and its regulatory enzyme HIF prolyl hydroxylase 2 in neonatal rat brain
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Comparison of embryonic development in birds and mammals: birth weight, time, and cost
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Fetal metabolic responses to hypoxia
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Tolerance of Human Placental Tissue to Severe Hypoxia and Its Relevance for Dual Ex Vivo Perfusion
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Antigenic identification of cells in spiral artery trophoblastic invasion: Validation of histologic studies by triple-antibody immunocytochemistry
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Correlation Between Umbilical Arterial Flow and Placental Morphology
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Untitled work
Kuzawa, C. W. (1998) · doi:10.1002/(sici)1096-8644(1998)107:27+

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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
IFPA Senior Award Lecture: Making sense of pre-eclampsia – Two placental causes of preeclampsia?
Redman, C. W. G., Sargent, I. L., & Staff, A. C. (2014) · Placenta · doi:10.1016/j.placenta.2013.12.008 · Cited by 437 · see citing works
“A review of the available evidence [33,34] suggests that oxygen tension in intervillous blood progressively declines with advancing gestational age.”
Redefining Preeclampsia Using Placenta-Derived Biomarkers
Staff, A. C., Benton, S. J., von Dadelszen, P., Roberts, J. M., Taylor, R. N., Powers, R. W., Jones, D. S., & Redman, C. W. G. (2013) · Hypertension · doi:10.1161/hypertensionaha.111.00250 · Cited by 375 · see citing works
“Intervillous pO 2 tends to decrease with advancing gestational age in normal pregnancy.(127) This may, at least in part, account for the falling circulating levels of PlGF from early in the third”
Background
Oxygen and oxidative stress in the perinatal period
Torres-Cuevas, I., Llorca, A. P., Illana, Á. S., Núñez‐Ramiro, A., Kuligowski, J., Cháfer‐Pericás, C., Cernada, M., Escobar, J., & Vento, M. (2017) · Redox Biology · doi:10.1016/j.redox.2017.03.011 · Cited by 247 · see citing works
“During fetal stage of development the rate of cell proliferation, division and vascularization occur at a slower rate coinciding with increased oxygenation [32,33].”
Background
Oxidative 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
Review: The placenta and developmental programming: Balancing fetal nutrient demands with maternal resource allocation
Burton, G. J., & Fowden, A. L. (2012) · Placenta · doi:10.1016/j.placenta.2011.11.013 · Cited by 177 · see citing works
The placental pursuit for an adequate oxidant balance between the mother and the fetus
Herrera, E. A., Krause, B. J., Ebensperger, G., Reyes, R. V., Casanello, P. C., Parra-Cordero, M., & Llanos, A. J. (2014) · Frontiers in Pharmacology · doi:10.3389/fphar.2014.00149 · Cited by 100 · see citing works
“However, after trophoblastic invasion and placental development, the fetus and placenta demands for oxygen increases, and are covered by maternal blood supply in the intervillous space (Jauniaux et al., 2006; Schneider, 2011; Murray, 2012).”
Background
Hypoxia alters the epigenetic profile in cultured human placental trophoblasts
Yuen, R. K. C., Chen, B., Blair, J. D., Robinson, W. P., & Nelson, D. M. (2013) · Epigenetics · doi:10.4161/epi.23400 · Cited by 85 · see citing works
“to continue at this level for the second and third trimesters.(3,4) This rise in pO 2 coincides with entry of maternal blood into the intervillous space between 10–12 weeks and perfusion of the treelike chorionic villi that mediate maternal-fetal exchange.”
Background
Aspirin inhibits expression of sFLT1 from human cytotrophoblasts induced by hypoxia, via cyclo-oxygenase 1
Li, C., Raikwar, N. S., Santillan, M. K. O., Santillan, D. A., & Thomas, C. P. (2015) · Placenta · doi:10.1016/j.placenta.2015.01.004 · Cited by 81 · see citing works
“Oxygen tension plays a key role in placental development, where the pO2 is 40e60 mmHg (5e8% oxygen) after 12 weeks gestation and continues at this level for the second and third trimesters [36,37].”
Background
Changes in mitochondrial respiration in the human placenta over gestation
Holland, O. J., Hickey, A. J., Alvsaker, A., Moran, S., Hedges, C. P., Chamley, L., & Perkins, A. V. (2017) · Placenta · doi:10.1016/j.placenta.2017.06.011 · Cited by 78 · see citing works
Placental hypoxia: The lesions of maternal malperfusion
Parks, W. T. (2014) · Seminars in Perinatology · doi:10.1053/j.semperi.2014.10.003 · Cited by 75 · see citing works
Pharmacological models and approaches for pathophysiological conditions associated with hypoxia and oxidative stress
Farías, J. G., Herrera, E. A., Carrasco‐Pozo, C., Sotomayor‐Zárate, R., Cruz, G., Morales, P., & Castillo, R. L. (2015) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2015.11.006 · Cited by 77 · see citing works
“This physiological condition decreases in tervillous perfusion, generating local hypoxia and oxidative stress (Schneider, 2011; Redman et al., 2014).”
Background
Melatonin: The watchdog of villous trophoblast homeostasis against hypoxia/reoxygenation-induced oxidative stress and apoptosis
Lanoix, D., Lacasse, A., Reiter, R. J., & Vaillancourt, C. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.07.010 · Cited by 74 · see citing works
Oxygen Supplementation in the Neonatal Period: Changing the Paradigm
Vento, M. (2014) · Neonatology · doi:10.1159/000360646 · Cited by 71 · see citing works
Blood Flow and Transport in the Human Placenta
Jensen, O. E., & Chernyavsky, I. L. (2018) · Annual Review of Fluid Mechanics · doi:10.1146/annurev-fluid-010518-040219 · Cited by 66 · see citing works
Three-dimensional modeling of human placental terminal villi
Mayo, R. P., Jones, D. S., Burton, G. J., & Oyen, M. L. (2016) · Placenta · doi:10.1016/j.placenta.2016.05.001 · Cited by 64 · see citing works
“Validations to support oxygen transport studies are 257 challenging since the experimental conditions, such as the concentration of oxygen, culture 258 medium and type of matrix, must be carefully adjusted [45].”
Background
Human Parvovirus B19 DNA Replication Induces a DNA Damage Response That Is Dispensable for Cell Cycle Arrest at Phase G 2 /M
Lou, S., Luo, Y., Cheng, F., Huang, Q., Shen, W., Kleiboeker, S. B., Tisdale, J. F., Liu, Z., & Qiu, J. (2012) · Journal of Virology · doi:10.1128/jvi.01007-12 · Cited by 50 · see citing works
“B19V infection of EPCs under hypoxic conditions in vitro mimics B19V infection of EPCs in the human bone marrow and fetal liver, where such hypoxic conditions exist (16, 52, 58, 67).”
Background
The xenoestrogens, bisphenol A and para-nonylphenol, decrease the expression of the ABCG2 transporter protein in human term placental explant cultures
Sieppi, E., Vähäkangas, K., Rautio, A., Ietta, F., Paulesu, L. R., & Myllynen, P. K. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.03.034 · Cited by 48 · see citing works
“In addition, a dependency of responses on gestational 7 age was seen in our study, which may be due to variation of oxygen tension, first trimester 8 placenta being under lower oxygen tension than term placenta (Schneider 2011).”
Background
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
Hypoxic Preconditioning Enhances Survival and Proangiogenic Capacity of Human First Trimester Chorionic Villus-Derived Mesenchymal Stem Cells for Fetal Tissue Engineering
Hao, D., He, C., Ma, B., Lankford, L., Reynaga, L., Farmer, D. L., Guo, F., & Wang, A. (2019) · Stem Cells International · doi:10.1155/2019/9695239 · Cited by 44 · see citing works
“In this study, we used 1% oxygen for CV-MSC preconditioning and simulated an ischemic environment to mimic the low oxygen concentration in the fetal environment and the further decrease in local oxygen concentration present after cell transplantation [81, 82].”
Method
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
“During the remainder of the gestational period, the average intervillous O2 concentration gradually declines from 60 mmHg to about 40 mmHg at term, as feto-placental O2 consumption progressively increases (Burton, 2009; Schneider, 2011).”
BackgroundInfluential
Travel to High Altitude during Pregnancy: Frequently Asked Questions and Recommendations for Clinicians
Jean, D., & MOORE, L. G. (2012) · High Altitude Medicine & Biology · doi:10.1089/ham.2012.1021 · Cited by 42 · see citing works
“However, in vitro studies have provided contradictory results (Schneider, 2011).”
MicroRNA-135b suppresses extravillous trophoblast-derived HTR-8/SVneo cell invasion by directly down regulating CXCL12 under low oxygen conditions
Tamaru, S., Mizuno, Y., Tochigi, H., Kajihara, T., Okazaki, Y., Okagaki, R., Kamei, Y., Ishihara, O., & Itakura, A. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.04.055 · Cited by 37 · see citing works
Intrauterine programming.
Sedaghat, K., Zahediasl, S., & Ghasemi, A. (2015) · Europe PMC (PubMed Central) · Cited by 38 · see citing works
Intrapartum cardiotocograph monitoring and perinatal outcomes for women at risk: Literature review
Small, K., Sidebotham, M., Fenwick, J., & Gamble, J. A. (2019) · Women and Birth · doi:10.1016/j.wombi.2019.10.002 · Cited by 35 · see citing works
Measuring venous blood oxygenation in fetal brain using susceptibility‐weighted imaging
Neelavalli, J., Jella, P. K., Krishnamurthy, U., Buch, S., Haacke, E. M., Yeo, L., Mody, S. S., Katkuri, Y., Bahado-Singh, R. O., Hassan, S. S., et al. (2013) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.24245 · Cited by 35 · see citing works
“[2], where u is the angle made by the long axis of the cylinder with the main magnetic field Bo (Fig.”
Background
Ontogenic changes in placental transthyretin
Patel, J., Landers, K., Li, H., Mortimer, R. H., & Richard, K. (2011) · Placenta · doi:10.1016/j.placenta.2011.09.007 · Cited by 34 · see citing works
“5% at 12weeks gestation, at which levels persist until delivery [17,18].”
Background
Intrauterine hypoxia: clinical consequences and therapeutic perspectives
Thompson, L. P., Crimmins, S. D., Telugu, B. P. V. L., & Turan, S. (2015) · Research and Reports in Neonatology · doi:10.2147/rrn.s57990 · Cited by 33 · see citing works
“Placental oxygenation may be reduced from inadequate O 2 delivery, placental insufficiency, and/ or abnormal spiral artery remodeling.(35,36) Regardless of the cause, the consequences of placenta hypoxia/ischemia are inadequate fetal oxygenation and placental pathology that contribute to a range of maternal symptoms o…”
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
“In the early second trimester, the de-plugging of the spiral arteries allows maternal blood to enter the intervillous space, causing an increase in oxygen tension to about 60 mmHg (w8% O2) [9].”
BackgroundInfluential
Oxygen Supplementation to Stabilize Preterm Infants in the Fetal to Neonatal Transition: No Satisfactory Answer
Torres-Cuevas, I., Cernada, M., Nuñez, A., Escobar, J., Kuligowski, J., Cháfer‐Pericás, C., & Vento, M. (2016) · Frontiers in Pediatrics · doi:10.3389/fped.2016.00029 · Cited by 31 · see citing works
“Hence, studies performed in human fetuses have shown that before the 12th week of gestation, the intervillous partial pressure of oxygen has a median value around 18–20 mmHg but rises steeply peaking at 60 mmHg around 14–16 weeks gestation, and thereafter decreases slowly reaching values of 45–48 mmHg at 36 weeks of g…”
Background
Oxygen saturation and heart rate in healthy term and late preterm infants with delayed cord clamping
Lara‐Cantón, I., Badurdeen, S., Dekker, J., Davis, P. G., Roberts, C. T., Pas, A. B. T., & Vento, M. (2022) · Pediatric Research · doi:10.1038/s41390-021-01805-y · Cited by 31 · see citing works
“In the second half of pregnancy, IVS partial pressure of oxygen slowly decreases from around 60mmHg in the 12th week of gestation to 45mmHg at term assuring a steady-state oxygenation of the fetus.(10) The limited supply of oxygen to the fetus requires adaptive changes in the placental structure together with changes…”
Background
Oxygen Sensitivity, Potassium Channels, and Regulation of Placental Vascular Tone
Wareing, M. (2014) · Microcirculation · doi:10.1111/micc.12069 · Cited by 30 · see citing works
“samples suggest that human fetoplacental blood vessels experience oxygenation levels at term similar to those recorded in the IVS (40-45mmHg; [18-21]); i.”
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
Manifestations of Hypoxia in the Second and Third Trimester Placenta
Parks, W. T. (2017) · Birth Defects Research · doi:10.1002/bdr2.1143 · Cited by 31 · see citing works
“Because normal maternal arterial blood has an oxygen level of around 90mm Hg, the fetus gestates in an environment that would be hypoxemic for a child or adult (Schneider, 2011).”
Background
Oxygen in the neonatal period: Oxidative stress, oxygen load and epigenetic changes
Lorente-Pozo, S., Llorca, A. P., Lara‐Cantón, I., Soláz-García, Á., García‐Giménez, J. L., Pallardó, F. V., & Vento, M. (2020) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2020.101090 · Cited by 29 · 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
Managing Preterm Infants in the First Minutes of Life
Vento, M., & Lista, G. (2015) · Paediatric Respiratory Reviews · doi:10.1016/j.prrv.2015.02.004 · Cited by 24 · see citing works
“In addition, conditions of the mother causing foetal hypoxaemia, such as preeclampsia or insulin dependent diabetes, also cause oxidative stress to the foetus, and provoke postnatal maladaptation [32].”
Background
Placenta and Placental Transport Function
Sadovsky, Y., & Jansson, T. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00039-9 · Cited by 24 · see citing works
Modelling preeclampsia: a comparative analysis of the common human trophoblast cell lines
Zhao, J., Chow, R. P., McLeese, R. H., Hookham, M. B., Lyons, T. J., & Yu, Y. (2020) · FASEB BioAdvances · doi:10.1096/fba.2020-00057 · Cited by 23 · see citing works
Hypoxia Promotes Osteogenesis of Human Placental-Derived Mesenchymal Stem Cells
Gu, Q., Gu, Y., Shi, Q., & Yang, H. (2016) · The Tohoku Journal of Experimental Medicine · doi:10.1620/tjem.239.287 · Cited by 23 · see citing works
“However, MSCs often reside in niches of low oxygen in vivo: 1-7% in BM, 10-15% in adipose tissue, and 2.5-8.5% in placenta (Bizzarri et al. 2006; Schneider 2011; Boyette et al. 2014).”
BackgroundInfluential
Evaluating the fetus at risk for cardiopulmonary compromise
Vento, M., & Teramo, K. A. (2013) · Seminars in Fetal and Neonatal Medicine · doi:10.1016/j.siny.2013.08.003 · Cited by 23 · see citing works
Oxygen impairs oligodendroglial development via oxidative stress and reduced expression of HIF-1α
Brill, C., Scheuer, T., Bührer, C., Endesfelder, S., & Schmitz, T. (2017) · Scientific Reports · doi:10.1038/srep43000 · Cited by 19 · see citing works
Targeting Oxygen in Term and Preterm Infants Starting at Birth
Vento, M., & Saugstad, O. D. (2019) · Clinics in Perinatology · doi:10.1016/j.clp.2019.05.013 · Cited by 18 · see citing works
Ethanol Impairs NRF2/Antioxidant and Growth Signaling in the Intact Placenta In Vivo and in Human Trophoblasts
Shanmugam, S., Patel, D., Wolpert, J. M., Keshvani, C., Liu, X., Bergeson, S. E., Kidambi, S., Mahimainathan, L., Henderson, G. I., & Narasimhan, M. (2019) · Biomolecules · doi:10.3390/biom9110669 · Cited by 18 · see citing works
“A healthy placenta is capable of generating significant base-line levels of reactive oxygen species (ROS) to execute specific physiological functions [25,26].”
Background
FtMt reduces oxidative stress-induced trophoblast cell dysfunction via the HIF-1α/VEGF signaling pathway
Xu, X., Ye, X., Zhu, M., Zhang, Q., Li, X., & Yan, J. (2023) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-023-05448-1 · Cited by 17 · see citing works
“Placental mitochondria are located in the gas transport region and are responsible for providing ATP to the placental tissues that mediate fetal growth, nutrient transport, and ion regulation [42].”
Background
Quantitative susceptibility mapping in the human fetus to measure blood oxygenation in the superior sagittal sinus
Yadav, B. K., Buch, S., Krishnamurthy, U., Jella, P. K., Hernandez‐Andrade, E. A., Trifan, A., Yeo, L., Hassan, S. S., Haacke, E. M., Romero, R. J., et al. (2018) · European Radiology · doi:10.1007/s00330-018-5735-1 · Cited by 17 · see citing works
“Adequate oxygen supply to the fetus is an essential component of its normal growth and development [1].”
Background
Estimating oxygen diffusive conductances of gas-exchange systems: A stereological approach illustrated with the human placenta
Mayhew, T. M. (2012) · Annals of Anatomy - Anatomischer Anzeiger · doi:10.1016/j.aanat.2012.08.002 · Cited by 17 · see citing works
The Regulation of Fatty Acid Oxidation in Human Preeclampsia
Shin, E.-K., Kang, H. Y., Yang, H. J., Jung, E., & Jeung, E. (2016) · Reproductive Sciences · doi:10.1177/1933719116641759 · Cited by 17 · see citing works
“In the second trimester occurring trophoblastic invasion and placental development, the fetus and placenta with the increased oxygen demand are covered by maternal blood supply in the intervillous space.(41,42) Additionally, the placental and fetal growth are closely related and dependent on increases in pO2.”
Background
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
“This observation is in line with what has been observed from the second to the third trimester of pregnancy in the intervillous space of the human placentas, where mean oxygen tension measured gradually declines [3,4,49].”
Result
Imaging putative foetal cerebral blood oxygenation using susceptibility weighted imaging (SWI)
Yadav, B. K., Krishnamurthy, U., Buch, S., Jella, P. K., Hernandez‐Andrade, E. A., Yeo, L., Korzeniewski, S. J., Trifan, A., Hassan, S. S., Haacke, E. M., et al. (2017) · European Radiology · doi:10.1007/s00330-017-5160-x · Cited by 14 · see citing works
Hypoxic-ischemic brain damage in premature newborns
Anurev, A., & Горбачев, В. И. (2019) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201911908263 · Cited by 14 · see citing works
The Liver X Receptor in Correlation with Other Nuclear Receptors in Spontaneous and Recurrent Abortions
Knabl, J., Pestka, A., Hüttenbrenner, R., Plösch, T., Ensenauer, R. E., Welbergen, L., Hutter, S., Karsten, M. M., & Jeschke, U. (2013) · PPAR Research · doi:10.1155/2013/575604 · Cited by 13 · see citing works
“In the first trimester, the maternal blood flow into the intervillous space is restricted creating a low oxygen environment for the trophoblast [15].”
Background
Placental Toxicity
Gupta, R. K., & Gupta, R. C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-804239-7.00068-8 · Cited by 13 · see citing works
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
Prediction of Severe Neonatal Hyperbilirubinemia Using Cord Blood Hydrogen Peroxide: A Prospective Study
Chou, H., Chien, C., Tsao, P., Hsieh, W., Chen, C., & Chang, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0086797 · Cited by 12 · see citing works
“Oxidation plays a role in the delivery process [17,18].”
Background
Subchronic perinatal asphyxia in rats: Embryo–foetal assessment of a new model of oxidative stress during critical period of development
Ujházy, E., Dubovický, M., Navarová, J., Sedláčková, N., Danihel, Ľ., Brucknerová, I., & Mach, M. (2013) · Food and Chemical Toxicology · doi:10.1016/j.fct.2013.07.023 · Cited by 12 · see citing works
“The embryo is highly sensitive to molecular oxygen, and an environment of low oxygen content is needed for the protection of the conceptus against oxidative stress (Schneider, 2011).”
Background
Placental toxicity
Gupta, R. K., & Gupta, R. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-89773-0.00068-0 · Cited by 9 · see citing works
β3‐Adrenoceptor Agonism to Mimic the Biological Effects of Intrauterine Hypoxia: Taking Great Strides Toward a Pharmacological Artificial Placenta
Filippi, L., Innocenti, F., Pascarella, F., Scaramuzzo, R. T., Morganti, R., Bagnoli, P., Cammalleri, M., Monte, M. D., Calvani, M., & Pini, A. (2024) · Medicinal Research Reviews · doi:10.1002/med.22092 · Cited by 7 · see citing works
“This interpretation is supported by samples drawn from the intervillous space of the human placenta, where the mean O 2 tension gradually decreases [84, 91, 126], and by evidence that placental O 2 consumption increases over time [60].”
Optimal oxygen saturation in extremely premature neonates
Zoban, P. (2019) · Physiological Research · doi:10.33549/physiolres.933987 · Cited by 7 · see citing works
“…that before the 12th week of gestation, the median value of intervillous PO2 is around 18-20 mmHg (2.4-2.7 kPa) and then steeply raises to median of 60 mmHg (8 kPa) at 14-18 weeks, and thereafter again decreases slowly to 45-48 mmHg (6-6.4 kPa) at 36 weeks gestation (Kiserud 2005, Schneider 2011).”
BackgroundInfluential
Real-time fetal monitoring using photoacoustic measurement of placental oxygen saturation in a rabbit hypoxia model
Okawa, K. S., Hirasawa, T., Okawa, S., Fujita, M., & Ishihara, M. (2024) · Placenta · doi:10.1016/j.placenta.2024.01.005 · Cited by 5 · see citing works
Can the neutrophil-to-lymphocyte ratio be used as an early marker of small fetuses for gestational age? A prospective study
Salomon, D., Fruscalzo, A., Boulvain, M., Féki, A., & Ali, N. B. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1439716 · Cited by 5 · see citing works
“It is between 10 and 12 weeks of pregnancy that the remodeling of the spiral arterioles takes place, and therefore maternal arterial circulation to the intervillous space is fully established (16).”
Background
Reference centiles for maternal placental growth factor levels at term from a low-risk population
Dunn, L., Sherrell, H. C., Bligh, L. N., Alsolai, A. A., Flatley, C. J., & Kumar, S. (2019) · Placenta · doi:10.1016/j.placenta.2019.08.086 · Cited by 5 · see citing works
Loss of high‐mobility group N5 contributes to the promotion of human endometrial stromal cell decidualization
Kimura, M., Kajihara, T., Mizuno, Y., Sato, T., & Ishihara, O. (2018) · Reproductive Medicine and Biology · doi:10.1002/rmb2.12226 · Cited by 5 · see citing works
Oxygen Consumption and General Carbohydrate Metabolism of the Fetus
Philipps, A. F. (2016) · Elsevier eBooks · doi:10.1016/b978-0-323-35214-7.00041-x · Cited by 4 · see citing works
The effect of mode of delivery on oxidative stress and antioxidant parameters in the mother, neonate and maternal milk
Tok, A., Özer, S., Özer, A., Kurutaş, E. B., Baylan, F. A., & Kılınç, M. (2025) · BMC Pregnancy and Childbirth · doi:10.1186/s12884-025-07832-5 · Cited by 3 · see citing works
“It is also known that these fluctuations cause increased OS in the placenta during an uncomplicated normal birth [5].”
Control of the heart rate of rat embryos during the organogenic period
Ritchie, H. E., Ragnerstam, C., Gustafsson, E., Jonsson, J. M., & Webster, W. S. (2016) · Hypoxia · doi:10.2147/hp.s115050 · Cited by 3 · see citing works
“These oxygen levels fall within the range reported for the placenta during the first trimester of pregnancy.(4) Oxygen tension in the human placenta is <20 mmHg up to 8 weeks gestation increasing to 50 mmHg at 12 weeks.”
Overview of Placenta Pathology
Govindavari, J. P., & Laury, A. R. (2024) · Springer eBooks · doi:10.1007/978-981-19-7696-4_14-1 · Cited by 2 · see citing works
Exposure to Treponema pallidum Alters Villous Histomorphology of Human Placentae
Tetteh‐Quarcoo, P. B., Twasam, J., Ahenkorah, J., Hottor, B. A., Dayie, N. T. K. D., Nyarko, S., Appiah, P. O., Afutu, E., Kotey, F. C. N., Donkor, E. S., et al. (2025) · Acta Microbiologica Hellenica · doi:10.3390/amh70030031 · Cited by 1 · see citing works
The Utility of Plasma Transthyretin and Antioxidants as aBiomarker of Early Pregnancy Loss - A Pilot Study
Sen, M., Goenka, D. M. L., Jha, M. D., Raj, M. V., Charles, M. S., Mala, K., & George, M. (2019) · Obsgyne Review Journal of Obstetric and Gynecology · doi:10.17511/joog.2019.i01.12 · Cited by 1 · see citing works
“5% at 12 weeks which remains stable until delivery [27, 28].”
Background
Impact of common pathogenetic mechanisms of preeclampsia and gestational diabetes mellitus on their clinical features and placental pathology
Shamarakova, M. V., Nizyaeva, N. V., Zayratyants, G. O., Boltovskaya, M. N., Артемьева, К. А., Аксенова, М. Г., Bochkov, V. V., Dobrokhotova, Y. E., & Михалева, Л. М. (2024) · CLINICAL AND EXPERIMENTAL MORPHOLOGY · doi:10.31088/cem2024.13.2.5-13 · Cited by 1 · see citing works
Präimplantation, Implantation und Plazentation
Schneider, H., Raio, L., Pollheimer, J., & Knöfler, M. (2016) · Springer eBooks · doi:10.1007/978-3-662-45064-2_1 · Cited by 1 · see citing works
Self-citation
Overview of Placenta Pathology
Govindavari, J. P., & Laury, A. R. (2019) · Springer eBooks · doi:10.1007/978-981-13-3019-3_14 · Cited by 1 · see citing works
DNA methylation studies of preeclampsia and related conditions
Blair, J. (2013) · cIRcle (University of British Columbia) · doi:10.14288/1.0074068 · Cited by 1 · see citing works
Energetics and oxygen transport mechanisms in embryos
Mortola, J. P. (2011) · Respiratory Physiology & Neurobiology · doi:10.1016/j.resp.2011.04.010
Stereological Studies on Transient Gas Exchangers with Emphasis on the Structure and Function of the Human Placenta in Normal and Compromised Pregnancies
Mayhew, T. M. (2015) · Springer eBooks · doi:10.1007/978-3-319-18392-3_10
Physiologie des Feten
Singer, D. (2017) · Springer eBooks · doi:10.1007/978-3-662-54375-7_7
Präimplantation, Implantation und Plazentation
Schneider, H., Raio, L., Pollheimer, J., & Knöfler, M. (2015) · Springer eBooks · doi:10.1007/978-3-662-44369-9_1-1
Self-citation
Intrauterine Aspects
Zabransky, S. (2013) · doi:10.1007/978-1-908517-90-6_2
Supplementary material A: Commentaries
Ainsworth, S. B. (2020) · Oxford University Press eBooks · doi:10.1093/med/9780198840787.005.0001
Overview of Placenta Pathology
Govindavari, J. P., & Laury, A. R. (2025) · Springer eBooks · doi:10.1007/978-981-97-4822-8_14
Association between unexplained recurrent pregnancy loss history and adverse neonatal outcomes among infertile women undergoing ART
Xing, G., Miao, X., Xia, L., Lin, J., Zhu, J., Tian, L., Zhao, Y., & Huang, J. (2025) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2025.105243
Additional file 1 of FtMt reduces oxidative stress-induced trophoblast cell dysfunction via the HIF-1α/VEGF signaling pathway
Xu, X., Ye, X., Zhu, M., Zhang, Q., Li, X., & Yan, J. (2024) · Figshare · doi:10.6084/m9.figshare.26572090
Revisiting the Functions of the Human Placenta in Health and Disease
Quaye, D., Appiah, P. O., Obiri, D., Ahenkorah, J., & Adu‐Bonsaffoh, K. (2026) · Current Obstetrics and Gynecology Reports · doi:10.1007/s13669-026-00487-9
“In addition, fetal hemoglobin enhances oxygen uptake by maintaining high oxygen affinity at relatively supporting effective gas transfer in both normoxic and physiologically low-oxygen environments characteristic of early gestation [18].”

Fetal oxygenation
Felis, S. (2023) · American Journal of Medical and Clinical Research & Reviews · doi:10.58372/2835-6276.1082 · Cited by 3 · see citing works
Review: Oxygen and trophoblast biology – A source of controversy
Tuuli, M. G., Longtine, M. S., & Nelson, D. M. (2011) · Placenta · doi:10.1016/j.placenta.2010.12.013 · Cited by 158 · see citing works
Oxygenation of the placenta and its role in pre-eclampsia
Huppertz, B. (2014) · Pregnancy Hypertension · doi:10.1016/j.preghy.2014.04.016 · Cited by 18 · 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
Le placenta humain et ses pathologies : l’oxygène en question
Challier, J.-C., & Uzan, S. (2003) · médecine/sciences · doi:10.1051/medsci/200319111111 · Cited by 22 · see citing works

Authors: Schneider, H.
Affiliations: University Hospital of Bern (CH)
Corresponding author: Schneider, Henning
ORCID: Schneider, Henning
Venue: Respiratory Physiology & Neurobiology
Publisher: Elsevier BV
Published: 2011-08
Volume: 178
Issue: 1
Pages: 51-58
ISSN: 1569-9048 (ISSN-L)
DOI: 10.1016/j.resp.2011.05.009
OpenAlex: W2021126174
Cited by: 84
References: 118
Citations by year: 2026: 1 · 2025: 4 · 2024: 7 · 2023: 2 · 2022: 3 · 2020: 5 · 2019: 9 · 2018: 3 · 2017: 7 · 2016: 9 · 2015: 8 · 2014: 7 · 2013: 10 · 2012: 5
FWCI: 1.50
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: Respiratory Physiology & Neurobiology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords: placental oxygenation, fetal oxygenation, intervillous space, trophoblast, maternal-fetal blood flow, chronic hypoxia, fetal growth restriction, miscarriage, perinatal hypoxia, pregnancy trimesters
MeSH terms: Embryo, Mammalian, Female, Fetus, Humans, Oxygen, Placenta, Pregnancy, Fetal Development

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Oxygenation of the placental–fetal unit in humans

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