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

ABSTRACT 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.

Download full-text


Available from: Graham J Burton, Dec 15, 2014
1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Early human placental and embryonic development occur in a physiologically low oxygen environment supported by histiotrophic secretions from endometrial glands. In this study, we compare the placental metabolomic profile of 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 or 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 were transcripts 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 stressed specimens retrieved after curettage. HIF-1α stabilisation 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 · 3.48 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The placenta is the exchange organ that regulates metabolic processes between the mother and her developing fetus. The adequate function of this organ is clearly vital for a physiologic gestational process and a healthy baby as final outcome. The umbilico-placental vasculature has the capacity to respond to variations in the materno-fetal milieu. Depending on the intensity and the extensity of the insult, these responses may be immediate-, mediate-, and long-lasting, deriving in potential morphostructural and functional changes later in life. These adjustments usually compensate the initial insults, but occasionally may switch to long-lasting remodeling and dysfunctional processes, arising maladaptation. One of the most challenging conditions in modern perinatology is hypoxia and oxidative stress during development, both disorders occurring in high-altitude and in low-altitude placental insufficiency. Hypoxia and oxidative stress may induce endothelial dysfunction and thus, reduction in the perfusion of the placenta and restriction in the fetal growth and development. This Review will focus on placental responses to hypoxic conditions, usually related with high-altitude and placental insufficiency, deriving in oxidative stress and vascular disorders, altering fetal and maternal health. Although day-to-day clinical practice, basic and clinical research are clearly providing evidence of the severe impact of oxygen deficiency and oxidative stress establishment during pregnancy, further research on umbilical and placental vascular function under these conditions is badly needed to clarify the myriad of questions still unsettled.
    Frontiers in Pharmacology 06/2014; 5:149. DOI:10.3389/fphar.2014.00149
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Study Question. To determine whether the umbilical cord insertion site of singleton pregnancies could be linked to the newborn birth weight at term and its individual growth potential achievement. Material and Methods. A cohort study including 528 records of term neonates was performed. Each neonate was assessed for growth adjusted for gestational age according to the infant's growth potential using the AUDIPOG module. We considered two categories of umbilical cord insertions: central and peripheral. Intrauterine growth restriction was defined as birth weight below the 10th percentile. Statistical analysis was performed using Chi-square, Student's t test, Wilcoxon test, ANOVA, and logistic regression. Results. We observed a total of 343 centrally inserted cords versus 185 peripheral cords. There were twice as many smokers in the mothers of the peripheral category compared to the centrally inserted ones. More importantly, we demonstrated that only 17/343 (5.0%) of infants with central cord insertion were growth restricted, compared to 37/185 (20.0%) of the infants born with a peripheral insertion. Neonates with centrally inserted cord were significantly heavier. Conclusion. The umbilical cord insertion site of singleton pregnancies is associated with the newborn's birth weight at term and its individual growth potential achievement.
    BioMed Research International 05/2014; 2014:341251. DOI:10.1155/2014/341251 · 2.71 Impact Factor