Placental Oxidative Stress: From Miscarriage to Preeclampsia

Department of Anatomy, University of Cambridge, Cambridge, United Kingdom.
Journal of the Society for Gynecologic Investigation (Impact Factor: 2.33). 10/2004; 11(6):342-52. DOI: 10.1016/j.jsgi.2004.03.003
Source: PubMed


To review the role of oxidative stress in two common placental-related disorders of pregnancy, miscarriage and preeclampsia.
Review of published literature.
Miscarriage and preeclampsia manifest at contrasting stages of pregnancy, yet both have their roots in deficient trophoblast invasion during early gestation. Early after implantation, endovascular trophoblast cells migrate down the lumens of spiral arteries, and are associated with their physiological conversion into flaccid conduits. Initially these cells occlude the arteries, limiting maternal blood flow into the placenta. The embryo therefore develops in a low oxygen environment, protecting differentiating cells from damaging free radicals. Once embryogenesis is complete, the maternal intervillous circulation becomes fully established, and intraplacental oxygen concentration rises threefold. Onset of the circulation is normally a progressive periphery-center phenomenon, and high levels of oxidative stress in the periphery may induce formation of the chorion laeve. If trophoblast invasion is severely impaired, plugging of the spiral arteries is incomplete, and onset of the maternal intervillous circulation is premature and widespread throughout the placenta. Syncytiotrophoblastic oxidative damage is extensive, and likely a major contributory factor to miscarriage. Between these two extremes will be found differing degrees of trophoblast invasion compatible with ongoing pregnancy but resulting in deficient conversion of the spiral arteries and an ischemia-reperfusion-type phenomenon. Placental perfusion will be impaired to a greater or lesser extent, generating commensurate placental oxidative stress that is a major contributory factor to preeclampsia.
Miscarriage, missed miscarriage, and early- and late-onset preeclampsia represent a spectrum of disorders secondary to deficient trophoblast invasion.

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    • "Although ROS and antioxidants remain in balance during a healthy pregnancy , and cellular damage is repaired effectively, this balance can be easily disrupted (Furness et al., 2011). High OS during the first trimester of pregnancy increases the risk of spontaneous abortion (Agarwal et al., 2006; Burton and Jauniaux, 2004), as it causes the premature oxygenation of the early embryonic environment, which should occur later in the pregnancy (Jauniaux et al., 2000). OS is involved in defective embryo development and retardation of embryo growth, preeclampsia, maternal hypertension, and the risk of preterm delivery (reviewed in Ruder et al., 2009). "
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    ABSTRACT: Objectives High level of oxidative stress (OS) during the first weeks of pregnancy is related to many serious pregnancy complications. Previous studies showed that body fluctuating asymmetry (FA) is related to OS level in men, suggesting that FA is a marker of oxidative balance in an individual. The aim of this study was to analyze if body FA was related to the level of biomarkers of OS in the first trimester of pregnancy.Methods The sample included 34 women in the first trimester of pregnancy, not smoking, and not exposed to toxins in their work environment. The composite FA and levels of two biomarkers of OS, 8-iso-ProstaglandinF2α (an indicator of oxidative damage to lipids) and 8-OH-dG (an indicator of oxidative damage to DNA) were measured. Factors that may affect the level of OS (vitamin supplementation, age, smoking, alcohol drinking, physical activity, and health condition) were controlled.ResultsThe levels of OS markers in the first trimester of pregnancy correlated positively with women's FA (r = 0.52, P = 0.002 for 8-OH-dG; r = 0.50; P = 0.003 for 8-iso-PGF2α level) and positively with body height (r = 0.37, P = 0.03 for 8-OH-dG level).Conclusion The level of OS is likely to be a substantial and important fitness trait, and FA may convey information on the level of OS in women. The result confirms that FA is an indicator of biological condition, as suggested by an evolutionary approach to morphological human traits perceived as attractive. Am. J. Hum. Biol., 2015. © 2015 Wiley Periodicals, Inc.
    American Journal of Human Biology 04/2015; DOI:10.1002/ajhb.22730 · 1.70 Impact Factor
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    • "udies suggested a definite paternalspecific risk of developing preeclampsia (Robillard et al., 1994). In fact, maternal exposure to paternal sperm and seminal plasma and the adaptation to them seem to play a role in the unbalanced immunoregulation at the maternal/placental interface promoting an inadequate trophoblast invasion of the placenta bed (Burton and Jauniaux, 0165-0378/© 2015 Elsevier Ireland Ltd. All rights reserved. 2004). Subsequently, an imbalance of circulating angiogenic factors occurs and results in maternal endothelial dysfunction, which induces the clinical syndrome (Mutter and Karumanchi, 2008). Interestingly, the unique immune environment at the maternal/fetal interface may contribute to the angiogenic balance necessary to maintain a healthy pr"
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    ABSTRACT: Several clinical and basic science reports have elucidated partial aspects of the pathophysiology of preeclampsia and have led many authors to conclude that different "subtypes" of the disease exist. All these subtypes share the main clinical features of the disease and present additional characteristics that define different clinical phenotypes. Nevertheless, immunological alterations, endothelial dysfunction, and insulin resistance constantly characterize this syndrome. These aspects are intimately related at a molecular level; thus, we propose an alternative approach to explaining biologically the main intracellular processes that occur in preeclampsia and this may yield an insight into the pathogenesis. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Journal of Reproductive Immunology 02/2015; 108. DOI:10.1016/j.jri.2015.01.009 · 2.82 Impact Factor
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    • "A major change takes place at the end of the first trimester when the maternal arterial circulation commences (Burton et al., 1999), and the oxygen tension within the intervillous space increases from 18 mmHg (equivalent to 2.5% O 2 ) at 8 weeks to 60 mmHg (8.5%) at 12 weeks (Jauniaux et al., 2000, 2003). This rise is associated with a burst of oxidative stress in the placental tissues, and with a robust increase in antioxidant defences (Burton and Jauniaux, 2004). "
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    ABSTRACT: 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.
    Molecular Human Reproduction 11/2014; 21(3). DOI:10.1093/molehr/gau105 · 3.75 Impact Factor
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