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Oxidative stress in the placenta

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Abstract

Pregnancy is a state of oxidative stress arising from increased placental mitochondrial activity and production of reactive oxygen species (ROS), mainly superoxide anion. The placenta also produces other ROS including nitric oxide, carbon monoxide, and peroxynitrite which have pronounced effects on placental function including trophoblast proliferation and differentiation and vascular reactivity. Excessive production of ROS may occur at certain windows in placental development and in pathologic pregnancies, such as those complicated by preeclampsia and/or IUGR, overpowering antioxidant defenses with deleterious outcome. In the first trimester, establishment of blood flow into the intervillous space is associated with a burst of oxidative stress. The inability to mount an effective antioxidant defense against this results in early pregnancy loss. In late gestation increased oxidative stress is seen in pregnancies complicated by diabetes, IUGR, and preeclampsia in association with increased trophoblast apoptosis and deportation and altered placental vascular reactivity. Evidence for this oxidative stress includes increased lipid peroxides and isoprostanes and decreased expression and activity of antioxidants. The interaction of nitric oxide and superoxide produces peroxynitrite, a powerful prooxidant with diverse deleterious effects including nitration of tyrosine residues on proteins thus altering function. Nitrative stress, subsequent to oxidative stress is seen in the placenta in preeclampsia and diabetes in association with altered placental function.

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References

  • Adams RH, Porras A, Alonso G, Jones M, Vintersten K, Panelli S, Valladares A, Perez L, Klein R, Nebreda AR (2000) Essential role of p38alpha MAP kinase in placental but not embryonic cardiovascular development. Mol Cell 6:109–116

    Article  CAS  PubMed  Google Scholar 

  • Allaire AD, Ballenger KA, Wells SR, McMahon MJ, Lessey BA (2000) Placental apoptosis in preeclampsia. Obstet Gynecol 96:271–276

    Article  CAS  PubMed  Google Scholar 

  • Al-Mehdi AB, Zhao G, Dodia C, Tozawa K, Costa K, Muzykantov V, Ross C, Blecha F, Dinauer M, Fisher AB (1998) Endothelial NADPH oxidase as the source of oxidants in lungs exposed to ischemia or high K+. Circ Res 83:730–737

    CAS  PubMed  Google Scholar 

  • Alsat E, Wyplosz P, Malassine A, Guibourdenche J, Porquet D, Nessmann C, Evain-Brion D (1996) Hypoxia impairs cell fusion and differentiation process in human cytotrophoblast, in vitro. J Cell Physiol 168:346–353

    Article  CAS  PubMed  Google Scholar 

  • Aly AS, Khandelwal M, Zhao J, Mehmet AH, Sammel MD, Parry S (2004) Neutrophils are stimulated by syncytiotrophoblast microvillous membranes to generate superoxide radicals in women with preeclampsia. Am J Obstet Gynecol 190:252–258

    Article  CAS  PubMed  Google Scholar 

  • Arbiser JL, Petros J, Klafter R, Govindajaran B, McLaughlin ER, Brown LF, Cohen C, Moses M, Kilroy S, Arnold RS, Lambeth JD (2002) Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc Natl Acad Sci U S A 99:715–720

    Article  CAS  PubMed  Google Scholar 

  • Aulak KS, Miyagi M, Yan L, West KA, Massillon D, Crabb JW, Stuehr DJ (2001) Proteomic method identifies proteins nitrated in vivo during inflammatory challenge. Proc Natl Acad Sci U S A 98:12056–12061

    Article  CAS  PubMed  Google Scholar 

  • Babior BM, Lambeth JD, Nauseef W (2002) The neutrophil NADPH oxidase. Arch Biochem Biophys 397:342–344

    Article  CAS  PubMed  Google Scholar 

  • Baker CS, Frost MT, Rimoldi O, Moore K, Halliwell B, Polak JM, Camici PG, Hall RJ (2002) Repetitive myocardial stunning in pigs is associated with an increased formation of reactive nitrogen species. Heart 87:77–78

    Article  CAS  PubMed  Google Scholar 

  • Balafanova Z, Bolli R, Zhang J, Zheng Y, Pass JM, Bhatnagar A, Tang XL, Wang O, Cardwell E, Ping P (2002) Nitric oxide (NO) induces nitration of protein kinase C epsilon (PKCepsilon), facilitating PKCepsilon translocation via enhanced PKCepsilon-RACK2 interactions: a novel mechanism of NO-triggered activation of PKCepsilon. J Biol Chem 277:15021–15027

    Article  CAS  PubMed  Google Scholar 

  • Barber A, Robson SC, Myatt L, Bulmer JN, Lyall F (2001) Heme oxygenase expression in human placenta and placental bed: reduced expression of placenta endothelial HO-2 in preeclampsia and fetal growth restriction. FASEB J 15:1158–1168

    Article  CAS  PubMed  Google Scholar 

  • Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and the ugly. Am J Physiol 271:C1424–C1437

    CAS  PubMed  Google Scholar 

  • Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci U S A 87:1620–1624

    CAS  PubMed  Google Scholar 

  • Beckman J, Ye Y, Anderson P, Chen J, Accqvitti M, Trapey M, White C (1994) Extensive nitration of protein tyrosines in human atherosclerosis detected by immunohistochemistry. Biol Chem 375:81–88

    Google Scholar 

  • Benkusky NA, Lewis SJ, Kooy NW (1999) Peroxynitrite-mediated attenuation of alpha- and beta-adrenoceptor agonist-induced vascular responses in vivo. Eur J Pharmacol 364:151–158

    Article  CAS  PubMed  Google Scholar 

  • Boyd PA (1984) Quantitative structure of the normal human placenta from 10 weeks of gestation to term. Early Hum Dev 9:297–307

    Article  CAS  PubMed  Google Scholar 

  • Brar SS, Corbin Z, Kennedy TP, Hemendinger R, Thornton L, Bommarius B, Arnold RS, Whorton AR, Sturrock AB, Huecksteadt TP, Quinn MT, Krenitsky K, Ardie KG, Lambeth JD, Hoidal JR (2003) NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU145 prostate cancer cells. Am J Physiol Cell Physiol

  • Caniggia I, Winter J, Lye SJ, Post M (2000) Oxygen and placental development during the first trimester: implications for the pathophysiology of pre-eclampsia. Placenta 21(suppl A):S25–S30

    Google Scholar 

  • Caraceni P, Ryu HS, van Thiel DH, Borle AB (1995) Source of oxygen free radicals produced by rat hepatocytes during postanoxic reoxygenation. Biochim Biophys Acta 1268:249–254

    Article  CAS  PubMed  Google Scholar 

  • Casasco A, Calligaro A, Casasco M, Tateo S, Icaro Cornaglia A, Reguzzoni M, Farina A (1997) Immunohistochemical localization of lipoperoxidation products in normal human placenta. Placenta 18:249–253

    CAS  PubMed  Google Scholar 

  • Cester N, Staffolani R, Rabini RA, Magnanelli R, Salvolini E, Galassi R, Mazzanti L, Romanini C (1994) Pregnancy induced hypertension: a role for peroxidation in microvillus plasma membranes. Mol Cell Biochem 131:151–155

    CAS  PubMed  Google Scholar 

  • Cha MS, Lee MJ, Je GH, Kwak JY (2001) Endogenous production of nitric oxide by vascular endothelial growth factor down-regulates proliferation of choriocarcinoma cells. Biochem Biophys Res Commun 282:1061–1066

    Article  CAS  PubMed  Google Scholar 

  • Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527–605

    CAS  PubMed  Google Scholar 

  • Chandel N, Budinger GR, Kemp RA, Schumacker PT (1995) Inhibition of cytochrome-c oxidase activity during prolonged hypoxia. Am J Physiol 268:L918–L925

    CAS  PubMed  Google Scholar 

  • Chen Q, Vazquez EJ, Moghaddas S, Hoppel CL, Lesnefsky EJ (2003) Production of reactive oxygen species by mitochondria: central role of complex III. J Biol Chem 278:36027–36031

    Article  CAS  PubMed  Google Scholar 

  • Conrad KP, Miles TM, Benyo DF (1998) Circulating levels of immunoreactive cytokines in women with preeclampsia. Am J Reprod Immunol 40:102–111

    CAS  PubMed  Google Scholar 

  • Davidge ST, Ojimba J, McLaughlin MK (1998) Vascular function in the vitamin E-deprived rat: an interaction between nitric oxide and superoxide anions. Hypertension 31:830–835

    CAS  PubMed  Google Scholar 

  • Dechend R, Viedt C, Muller DN, Ugele B, Brandes RP, Wallukat G, Park JK, Janke J, Barta P, Theuer J, Fiebeler A, Homuth V, Dietz R, Haller H, Kreuzer J, Luft FC (2003) AT1 receptor agonistic antibodies from preeclamptic patients stimulate NADPH oxidase. Circulation 107:1632–1639

    Article  CAS  PubMed  Google Scholar 

  • De Deken X, Wang D, Many MC, Costagliola S, Libert F, Vassart G, Dumont JE, Miot F (2000) Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem 275:23227–23233

    Article  PubMed  Google Scholar 

  • Eis AL, Brockman DE, Pollock JS, Myatt L (1995) Immunohistochemical localization of endothelial nitric oxide synthase in human villous and extravillous trophoblast populations and expression during syncytiotrophoblast formation in vitro. Placenta 16:113–126

    Article  CAS  PubMed  Google Scholar 

  • Frendo JL, Therond P, Bird T, Massin N, Muller F, Guibourdenche J, Luton D, Vidaud M, Anderson WB, Evain-Brion D (2001) Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation. Endocrinology 142:3638–3648

    Article  CAS  PubMed  Google Scholar 

  • Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal-Ginard B, Anversa P (2000) Myocardial cell death in human diabetes. Circ Res 87:1123–1132

    CAS  PubMed  Google Scholar 

  • Garner P, D’Alton M, Dudley D, Huard P, Hardie M (1990) Preeclampsia in diabetic pregnancies. Am J Obstet Gynecol 162:505–508

    Google Scholar 

  • Genbacev O, Joslin R, Damsky CH, Polliotti BM, Fisher SJ (1996) Hypoxia alters early gestation human cytotrophoblast differentiation/invasion in vitro and models the placental defects that occur in preeclampsia. J Clin Invest 97:540–550

    CAS  PubMed  Google Scholar 

  • Genbacev O, Zhou Y, Ludlow JW, Fisher SJ (1997) Regulation of human placental development by oxygen tension. Science 277:1669–1672

    Article  CAS  PubMed  Google Scholar 

  • Gervasi MT, Chaiworapongsa T, Pacora P, Naccasha N, Yoon BH, Maymon E, Romero R (2001) Phenotypic and metabolic characteristics of monocytes and granulocytes in preeclampsia. Am J Obstet Gynecol 185:792–797

    Article  CAS  PubMed  Google Scholar 

  • Giroux S, Tremblay M, Bernard D, Cardin-Girard JF, Aubry S, Larouche L, Rousseau S, Huot J, Landry J, Jeannotte L, Charron J (1999) Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Curr Biol 9:369–372

    Article  CAS  PubMed  Google Scholar 

  • Gole MD, Souza JM, Choi I, Hertkorn C, Malcolm S, Foust RF III, Finkel B, Lanken PN, Ischiropoulos H (2000) Plasma proteins modified by tyrosine nitration in acute respiratory distress syndrome. Am J Physiol Lung Cell Mol Physiol 278:L961–L967

    CAS  PubMed  Google Scholar 

  • Gow AJ, Duran D, Malcolm S, Ischiropoulos H (1996) Effects of peroxynitrite-induced protein modifications on tyrosine phosphorylation and degradation. FEBS Lett 385:63–66

    Article  CAS  PubMed  Google Scholar 

  • Greenacre SA, Ischiropoulos H (2001) Tyrosine nitration: localisation, quantification, consequences for protein function and signal transduction. Free Radic Res 34:541–581

    CAS  PubMed  Google Scholar 

  • Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501

    CAS  PubMed  Google Scholar 

  • Haddad IY, Pataki G, Hu P, Galliani C, Beckman JS, Matalon S (1994) Quantitation of nitrotyrosine levels in lung sections of patients and animals with acute lung injury. J Clin Invest 94:2407–2413

    CAS  PubMed  Google Scholar 

  • Hassoun PM, Yu FS, Shedd AL, Zulueta JJ, Thannickal VJ, Lanzillo JJ, Fanburg BL (1994) Regulation of endothelial cell xanthine dehydrogenase xanthine oxidase gene expression by oxygen tension. Am J Physiol 266:L163–L171

    CAS  PubMed  Google Scholar 

  • Hauser S, Weich HA (1993) A heparin-binding form of placenta growth factor (PlGF-2) is expressed in human umbilical vein endothelial cells and in placenta. Growth Factors 9:259–268

    CAS  PubMed  Google Scholar 

  • Hempstock J, Bao YP, Bar-Issac M, Segaren N, Watson AL, Charnock-Jones DS, Jauniaux E, Burton GJ (2003a) Intralobular differences in antioxidant enzyme expression and activity reflect the pattern of maternal arterial bloodflow within the human placenta. Placenta 24:517–523

    Article  CAS  PubMed  Google Scholar 

  • Hempstock J, Jauniaux E, Greenwold N, Burton GJ (2003b) The contribution of placental oxidative stress to early pregnancy failure. Hum Pathol 34:1265–1275

    Article  CAS  PubMed  Google Scholar 

  • Hoang VM, Foulk R, Clauser K, Burlingame A, Gibson BW, Fisher SJ (2001) Functional proteomics: examining the effects of hypoxia on the cytotrophoblast protein repertoire. Biochemistry 40:4077–4086

    Article  CAS  PubMed  Google Scholar 

  • Honing ML, Morrison PJ, Banga JD, Stroes ES, Rabelink TJ (1998) Nitric oxide availability in diabetes mellitus. Diabetes Metab Rev 14:241–249

    Article  CAS  PubMed  Google Scholar 

  • Hung TH, Skepper JN, Burton GJ (2001) In vitro ischemia-reperfusion injury in term human placenta as a model for oxidative stress in pathological pregnancies. Am J Pathol 159:1031–1043

    CAS  PubMed  Google Scholar 

  • Huppertz B, Kingdom J, Caniggia I, Desoye G, Black S, Korr H, Kaufmann P (2003) Hypoxia favours necrotic versus apoptotic shedding of placental syncytiotrophoblast into the maternal circulation. Placenta 24:181–190

    Article  CAS  PubMed  Google Scholar 

  • Ischiropoulos H (1998) Biological tyrosine nitration: a pathophysiological function of nitric oxide and reactive oxygen species. Arch Biochem Biophys 356:1–11

    Article  CAS  PubMed  Google Scholar 

  • Ischiropoulos H, Zhu L, Chen J, Tsai M, Martin JC, Smith CD, Beckman JS (1992) Peroxynitrite-mediated tyrosine nitration catalyzed by superoxide dismutase. Arch Biochem Biophys 298:431–437

    CAS  PubMed  Google Scholar 

  • Ishihara N, Matsuo H, Murakoshi H, Laoag-Fernandez JB, Samoto T, Maruo T (2002) Increased apoptosis in the syncytiotrophoblast in human term placentas complicated by either preeclampsia or intrauterine growth retardation. Am J Obstet Gynecol 186:158–166

    Article  PubMed  Google Scholar 

  • Jauniaux E, Watson AL, Hempstock J, Bao YP, Skepper JN, Burton GJ (2000) Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure. Am J Pathol 157:2111–2122

    CAS  PubMed  Google Scholar 

  • Jauniaux E, Greenwold N, Hempstock J, Burton GJ (2003) Comparison of ultrasonographic and Doppler mapping of the intervillous circulation in normal and abnormal early pregnancies. Fertil Steril 79:100–106

    Article  PubMed  Google Scholar 

  • Kajstura J, Fiordaliso F, Andreoli AM, Li B, Chimenti S, Medow MS, Limana F, Nadal-Ginard B, Leri A, Anversa P (2001) IGF-1 overexpression inhibits the development of diabetic cardiomyopathy and angiotensin II-mediated oxidative stress. Diabetes 50:1414–1424

    CAS  PubMed  Google Scholar 

  • Khaliq A, Li XF, Shams M, Sisi P, Acevedo CA, Whittle MJ, Weich H, Ahmed A (1996) Localisation of placenta growth factor (PIGF) in human term placenta. Growth Factors 13:243–250, color plates I–II pre bk cov

    CAS  PubMed  Google Scholar 

  • Kilani RT, Mackova M, Davidge ST, Guilbert LJ (2003) Effect of oxygen levels in villous trophoblast apoptosis. Placenta 24:826–834

    Article  CAS  PubMed  Google Scholar 

  • Knapen MF, Peters WH, Mulder TP, Merkus HM, Jansen JB, Steegers EA (1999) Glutathione and glutathione-related enzymes in decidua and placenta of controls and women with pre-eclampsia. Placenta 20:541–546

    Article  CAS  PubMed  Google Scholar 

  • Kossenjans W, Eis A, Sahay R, Brockman D, Myatt L (2000) Role of peroxynitrite in altered fetal-placental vascular reactivity in diabetes or preeclampsia. Am J Physiol Heart Circ Physiol 278:H1311–H1319

    CAS  PubMed  Google Scholar 

  • Kudin AP, Bimpong-Buta NY, Vielhaber S, Elger CE, Kunz WS (2004) Characterization of superoxide-producing sites in isolated brain mitochondria. J Biol Chem 279:4127–4135

    Article  CAS  PubMed  Google Scholar 

  • Kudo Y, Boyd CA, Sargent IL, Redman CW (2003) Hypoxia alters expression and function of syncytin and its receptor during trophoblast cell fusion of human placental BeWo cells: implications for impaired trophoblast syncytialisation in pre-eclampsia. Biochim Biophys Acta 1638:63–71

    Article  CAS  PubMed  Google Scholar 

  • Kuo WN, Kanadia RN, Shanbhag VP, Toro R (1999) Denitration of peroxynitrite-treated proteins by ‘protein nitratases’ from rat brain and heart. Mol Cell Biochem 201:11–16

    Article  CAS  PubMed  Google Scholar 

  • Kuo WN, Kocis JM, Webb JK (2002) Protein denitration/modification by Escherichia coli nitrate reductase and mammalian cytochrome P-450 reductase. Front Biosci 7:a9–a14

    CAS  PubMed  Google Scholar 

  • Kuroki M, Voest EE, Amano S, Beerepoot LV, Takashima S, Tolentino M, Kim RY, Rohan RM, Colby KA, Yeo KT, Adamis AP (1996) Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo. J Clin Invest 98:1667–1675

    CAS  PubMed  Google Scholar 

  • Lee CI, Liu X, Zweier JL (2000) Regulation of xanthine oxidase by nitric oxide and peroxynitrite. J Biol Chem 275:9369–9376

    Article  CAS  PubMed  Google Scholar 

  • Lee VM, Quinn PA, Jennings SC, Ng LL (2003) NADPH oxidase activity in preeclampsia with immortalized lymphoblasts used as models. Hypertension 41:925–931

    Article  CAS  PubMed  Google Scholar 

  • Leung DN, Smith SC, To KF, Sahota DS, Baker PN (2001) Increased placental apoptosis in pregnancies complicated by preeclampsia. Am J Obstet Gynecol 184:1249–1250

    Article  CAS  PubMed  Google Scholar 

  • Li C, Wright MM, Jackson RM (2002) Reactive species mediated injury of human lung epithelial cells after hypoxia-reoxygenation. Exp Lung Res 28:373–389

    Article  PubMed  Google Scholar 

  • Li N, Ragheb K, Lawler G, Sturgis J, Rajwa B, Melendez JA, Robinson JP (2003) Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. J Biol Chem 278:8516–8525

    Article  CAS  PubMed  Google Scholar 

  • Liu P, Hock CE, Nagele R, Wong PY (1997) Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am J Physiol 272:H2327–H2336

    CAS  PubMed  Google Scholar 

  • Lyall F (2003) Development of the utero-placental circulation: the role of carbon monoxide and nitric oxide in trophoblast invasion and spiral artery transformation. Microsc Res Tech 60:402–411

    Article  CAS  PubMed  Google Scholar 

  • Lyall F, Gibson JL, Greer IA, Brockman DE, Eis AL, Myatt L (1998) Increased nitrotyrosine in the diabetic placenta: evidence for oxidative stress. Diabetes Care 21:1753–1758

    CAS  PubMed  Google Scholar 

  • Lyall F, Barber A, Myatt L, Bulmer JN, Robson SC (2000) Hemeoxygenase expression in human placenta and placental bed implies a role in regulation of trophoblast invasion and placental function. FASEB J 14:208–219

    CAS  PubMed  Google Scholar 

  • MacMillan-Crow LA, Crow JP, Thompson JA (1998) Peroxynitrite-mediated inactivation of manganese superoxide dismutase involves nitration and oxidation of critical tyrosine residues. Biochemistry 37:1613–1622

    Article  CAS  PubMed  Google Scholar 

  • Madazli R, Benian A, Aydin S, Uzun H, Tolun N (2002) The plasma and placental levels of malondialdehyde, glutathione and superoxide dismutase in pre-eclampsia. J Obstet Gynaecol 22:477–480

    Article  CAS  PubMed  Google Scholar 

  • Maglione D, Guerriero V, Viglietto G, Delli-Bovi P, Persico MG (1991) Isolation of a human placenta cDNA coding for a protein related to the vascular permeability factor. Proc Natl Acad Sci U S A 88:9267–9271

    CAS  PubMed  Google Scholar 

  • Maglione D, Guerriero V, Viglietto G, Ferraro MG, Aprelikova O, Alitalo K, Del Vecchio S, Lei KJ, Chou JY, Persico MG (1993) Two alternative mRNAs coding for the angiogenic factor, placenta growth factor (PlGF), are transcribed from a single gene of chromosome 14. Oncogene 8:925–931

    CAS  PubMed  Google Scholar 

  • Manes C (2001) Human placental NAD(P)H oxidase: solubilization and properties. Placenta 22:58–63

    Article  CAS  PubMed  Google Scholar 

  • Many A, Westerhausen-Larson A, Kanbour-Shakir A, Roberts JM (1996) Xanthine oxidase/dehydrogenase is present in human placenta. Placenta 17:361–365

    Article  CAS  PubMed  Google Scholar 

  • Many A, Hubel CA, Fisher SJ, Roberts JM, Zhou Y (2000) Invasive cytotrophoblasts manifest evidence of oxidative stress in preeclampsia. Am J Pathol 156:321–331

    CAS  PubMed  Google Scholar 

  • Martin D, Conrad KP (2000) Expression of endothelial nitric oxide synthase by extravillous trophoblast cells in the human placenta. Placenta 21:23–31

    Article  CAS  PubMed  Google Scholar 

  • Matsubara S, Sato I (2001) Enzyme histochemically detectable NAD(P)H oxidase in human placental trophoblasts: normal, preeclamptic, and fetal growth restriction-complicated pregnancy. Histochem Cell Biol 116:1–7

    CAS  PubMed  Google Scholar 

  • Matsubara S, Minakami H, Sato I, Saito T (1997) Decrease in cytochrome c oxidase activity detected cytochemically in the placental trophoblast of patients with pre-eclampsia. Placenta 18:255–259

    CAS  PubMed  Google Scholar 

  • Mayhew TM, Leach L, McGee R, Ismail WW, Myklebust R, Lammiman MJ (1999) Proliferation, differentiation and apoptosis in villous trophoblast at 13–41 weeks of gestation (including observations on annulate lamellae and nuclear pore complexes). Placenta 20:407–422

    Article  CAS  PubMed  Google Scholar 

  • McAleer MF, Tuan RS (2001) Metallothionein protects against severe oxidative stress-induced apoptosis of human trophoblastic cells. In Vitro Mol Toxicol 14:219–231

    Article  CAS  Google Scholar 

  • McLean M, Bowman M, Clifton V, Smith R, Grossman AB (2000) Expression of the heme oxygenase-carbon monoxide signalling system in human placenta. J Clin Endocrinol Metab 85:2345–2349

    Article  CAS  PubMed  Google Scholar 

  • Mihm MJ, Coyle CM, Schanbacher BL, Weinstein DM, Bauer JA (2001a) Peroxynitrite induced nitration and inactivation of myofibrillar creatine kinase in experimental heart failure. Cardiovasc Res 49:798–807

    Article  CAS  PubMed  Google Scholar 

  • Mihm MJ, Yu F, Carnes CA, Reiser PJ, McCarthy PM, Van Wagoner DR, Bauer JA (2001b) Impaired myofibrillar energetics and oxidative injury during human atrial fibrillation. Circulation 104:174–180

    CAS  PubMed  Google Scholar 

  • Moncada S, Palmer RM, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142

    CAS  PubMed  Google Scholar 

  • Morris JM, Gopaul NK, Endresen MJ, Knight M, Linton EA, Dhir S, Anggard EE, Redman CW (1998) Circulating markers of oxidative stress are raised in normal pregnancy and pre-eclampsia. Br J Obstet Gynaecol 105:1195–1199

    CAS  PubMed  Google Scholar 

  • Mudgett JS, Ding J, Guh-Siesel L, Chartrain NA, Yang L, Gopal S, Shen MM (2000) Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proc Natl Acad Sci U S A 97:10454–10459

    Article  CAS  PubMed  Google Scholar 

  • Mutlu-Turkoglu U, Aykac-Toker G, Ibrahimoglu L, Ademoglu E, Uysal M (1999) Plasma nitric oxide metabolites and lipid peroxide levels in preeclamptic pregnant women before and after delivery. Gynecol Obstet Invest 48:247–250

    Article  CAS  PubMed  Google Scholar 

  • Myatt L, Brewer A, Brockman DE (1991) The action of nitric oxide in the perfused human fetal-placental circulation. Am J Obstet Gynecol 164:687–692

    CAS  PubMed  Google Scholar 

  • Myatt L, Rosenfield RB, Eis AL, Brockman DE, Greer I, Lyall F (1996) Nitrotyrosine residues in placenta. Evidence of peroxynitrite formation and action. Hypertension 28:488–493

    CAS  PubMed  Google Scholar 

  • Myatt L, Eis AL, Brockman DE, Greer IA, Lyall F (1997a) Endothelial nitric oxide synthase in placental villous tissue from normal, pre-eclamptic and intrauterine growth restricted pregnancies. Hum Reprod 12:167–172

    Article  CAS  PubMed  Google Scholar 

  • Myatt L, Eis AL, Brockman DE, Kossenjans W, Greer I, Lyall F (1997b) Inducible (type II) nitric oxide synthase in human placental villous tissue of normotensive, pre-eclamptic and intrauterine growth-restricted pregnancies. Placenta 18:261–268

    Article  CAS  PubMed  Google Scholar 

  • Myatt L, Eis AL, Brockman DE, Kossenjans W, Greer IA, Lyall F (1997c) Differential localization of superoxide dismutase isoforms in placental villous tissue of normotensive, pre-eclamptic, and intrauterine growth-restricted pregnancies. J Histochem Cytochem 45:1433–1438

    CAS  PubMed  Google Scholar 

  • Ohyama K, Yuan B, Bessho T, Yamakawa T (2001) Progressive apoptosis in chorion laeve trophoblast cells of human fetal membrane tissues during in vitro incubation is suppressed by antioxidative reagents. Eur J Biochem 268:6182–6189

    Article  CAS  PubMed  Google Scholar 

  • Partridge CA, Blumenstock FA, Malik AB (1992) Pulmonary microvascular endothelial cells constitutively release xanthine oxidase. Arch Biochem Biophys 294:184–187

    CAS  PubMed  Google Scholar 

  • Poranen AK, Ekblad U, Uotila P, Ahotupa M (1998) The effect of vitamin C and E on placental lipid peroxidation and antioxidative enzymes in perfused placenta. Acta Obstet Gynecol Scand 77:372–376

    Article  CAS  PubMed  Google Scholar 

  • Radi R, Beckman JS, Bush KM, Freeman BA (1991) Peroxynitrite-induced membrane lipid peroxidation: the cytotoxic potential of superoxide and nitric oxide. Arch Biochem Biophys 288:481–487

    CAS  PubMed  Google Scholar 

  • Radi R, Rodriguez M, Castro L, Telleri R (1994) Inhibition of mitochondrial electron transport by peroxynitrite. Arch Biochem Biophys 308:89–95

    Article  CAS  PubMed  Google Scholar 

  • Read MA, Leitch IM, Giles WB, Bisits AM, Boura AL, Walters WA (1999) U46619-mediated vasoconstriction of the fetal placental vasculature in vitro in normal and hypertensive pregnancies. J Hypertens 17:389–396

    Article  CAS  PubMed  Google Scholar 

  • Redman CW, Sargent IL (2000) Placental debris, oxidative stress and pre-eclampsia. Placenta 21:597–602

    Article  CAS  PubMed  Google Scholar 

  • Robinson VK, Sato E, Nelson DK, Camhi SL, Robbins RA, Hoyt JC (2001) Peroxynitrite inhibits inducible (type 2) nitric oxide synthase in murine lung epithelial cells in vitro. Free Radic Biol Med 30:986–991

    Article  CAS  PubMed  Google Scholar 

  • Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, Packer L (2001) The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 17:189–212

    Article  CAS  PubMed  Google Scholar 

  • Sen DK, Kaufmann P, Schweikhart G (1979) Classification of human placental villi. II. Morphometry. Cell Tissue Res 200:425–434

    CAS  PubMed  Google Scholar 

  • Shibata E, Ejima K, Nanri H, Toki N, Koyama C, Ikeda M, Kashimura M (2001) Enhanced protein levels of protein thiol/disulphide oxidoreductases in placentae from pre-eclamptic subjects. Placenta 22:566–572

    Article  CAS  PubMed  Google Scholar 

  • Shore VH, Wang TH, Wang CL, Torry RJ, Caudle MR, Torry DS (1997) Vascular endothelial growth factor, placenta growth factor and their receptors in isolated human trophoblast. Placenta 18:657–665

    Article  CAS  PubMed  Google Scholar 

  • Sikkema JM, van Rijn BB, Franx A, Bruinse HW, de Roos R, Stroes ES, van Faassen EE (2001) Placental superoxide is increased in pre-eclampsia. Placenta 22:304–308

    Article  CAS  PubMed  Google Scholar 

  • Smith SC, Baker PN, Symonds EM (1997a) Increased placental apoptosis in intrauterine growth restriction. Am J Obstet Gynecol 177:1395–1401

    CAS  PubMed  Google Scholar 

  • Smith SC, Baker PN, Symonds EM (1997b) Placental apoptosis in normal human pregnancy. Am J Obstet Gynecol 177:57–65

    CAS  PubMed  Google Scholar 

  • Smith SC, Guilbert LJ, Yui J, Baker PN, Davidge ST (1999) The role of reactive nitrogen/oxygen intermediates in cytokine-induced trophoblast apoptosis. Placenta 20:309–315

    Article  CAS  PubMed  Google Scholar 

  • Souren JE, Van Der Mast C, Van Wijk R (1997) NADPH-oxidase-dependent superoxide production by myocyte-derived H9c2 cells: influence of ischemia, heat shock, cycloheximide and cytochalasin D. J Mol Cell Cardiol 29:2803–2812

    Article  CAS  PubMed  Google Scholar 

  • Spranger M, Kiprianova I, Krempien S, Schwab S (1998) Reoxygenation increases the release of reactive oxygen intermediates in murine microglia. J Cereb Blood Flow Metab 18:670–674

    Article  CAS  PubMed  Google Scholar 

  • Tames F, Mackness M, Arrol S, Laing I, Durrington P (1992) Non-enzymatic glycation of apolipoprotein B in the sera of diabetic and non-diabetic subjects. Atherosclerosis 93:237–244

    CAS  PubMed  Google Scholar 

  • Taylor CM, Stevens H, Anthony FW, Wheeler T (1997) Influence of hypoxia on vascular endothelial growth factor and chorionic gonadotrophin production in the trophoblast-derived cell lines: JEG, JAr and BeWo. Placenta 18:451–458

    CAS  PubMed  Google Scholar 

  • Terada LS, Beehler CJ, Banerjee A, Brown JM, Grosso MA, Harken AH, McCord JM, Repine JE (1988) Hyperoxia and self- or neutrophil-generated O2 metabolites inactivate xanthine oxidase. J Appl Physiol 65:2349–2353

    CAS  PubMed  Google Scholar 

  • Torres M (2003) Mitogen-activated protein kinase pathways in redox signaling. Front Biosci 8:d369–d391

    CAS  PubMed  Google Scholar 

  • Turko IV, Marcondes S, Murad F (2001) Diabetes-associated nitration of tyrosine and inactivation of succinyl-CoA:3-oxoacid CoA-transferase. Am J Physiol Heart Circ Physiol 281:H2289–H2294

    CAS  PubMed  Google Scholar 

  • van Kreel BK, van Dijk JP (1977) Transport of uric acid and hypoxanthine across the isolated guinea pig placenta. Biol Neonate 32:260–265

    PubMed  Google Scholar 

  • Vaughan JE, Walsh SW (2002) Oxidative stress reproduces placental abnormalities of preeclampsia. Hypertens Pregnancy 21:205–223

    Article  CAS  PubMed  Google Scholar 

  • Villa LM, Salas E, Darley-Usmar VM, Radomski MW, Moncada S (1994) Peroxynitrite induces both vasodilatation and impaired vascular relaxation in the isolated perfused rat heart. Proc Natl Acad Sci U S A 91:12383–12387

    CAS  PubMed  Google Scholar 

  • Vuorela P, Hatva E, Lymboussaki A, Kaipainen A, Joukov V, Persico MG, Alitalo K, Halmesmaki E (1997) Expression of vascular endothelial growth factor and placenta growth factor in human placenta. Biol Reprod 56:489–494

    CAS  PubMed  Google Scholar 

  • Wajner M, Harkness RA (1989) Distribution of xanthine dehydrogenase and oxidase activities in human and rabbit tissues. Biochim Biophys Acta 991:79–84

    Article  CAS  PubMed  Google Scholar 

  • Walsh SW, Vaughan JE, Wang Y, Roberts LJ II (2000) Placental isoprostane is significantly increased in preeclampsia. FASEB J 14:1289–1296

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Walsh SW (1996a) Antioxidant activities and mRNA expression of superoxide dismutase, catalase, and glutathione peroxidase in normal and preeclamptic placentas. J Soc Gynecol Investig 3:179–184

    CAS  PubMed  Google Scholar 

  • Wang Y, Walsh SW (1996b) TNF alpha concentrations and mRNA expression are increased in preeclamptic placentas. J Reprod Immunol 32:157–169

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Walsh SW (1998) Placental mitochondria as a source of oxidative stress in pre-eclampsia. Placenta 19:581–586

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Walsh SW (2001) Increased superoxide generation is associated with decreased superoxide dismutase activity and mRNA expression in placental trophoblast cells in pre-eclampsia. Placenta 22:206–212

    Article  CAS  PubMed  Google Scholar 

  • Wang P, Zweier JL (1996) Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury. J Biol Chem 271:29223–29230

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Gu Y, Philibert L, Lucas MJ (2001) Neutrophil activation induced by placental factors in normal and pre-eclamptic pregnancies in vitro. Placenta 22:560–565

    Article  CAS  PubMed  Google Scholar 

  • Watson AL, Skepper JN, Jauniaux E, Burton GJ (1998) Susceptibility of human placental syncytiotrophoblastic mitochondria to oxygen-mediated damage in relation to gestational age. J Clin Endocrinol Metab 83:1697–1705

    Article  CAS  PubMed  Google Scholar 

  • Waypa GB, Chandel NS, Schumacker PT (2001) Model for hypoxic pulmonary vasoconstriction involving mitochondrial oxygen sensing. Circ Res 88:1259–1266

    CAS  PubMed  Google Scholar 

  • Wice B, Menton D, Geuze H, Schwartz AL (1990) Modulators of cyclic AMP metabolism induce syncytiotrophoblast formation in vitro. Exp Cell Res 186:306–316

    CAS  PubMed  Google Scholar 

  • Wilkes BM, Mento PF, Hollander AM (1994) Reduced thromboxane receptor affinity and vasoconstrictor responses in placentae from diabetic pregnancies. Placenta 15:845–855

    CAS  PubMed  Google Scholar 

  • Wisdom SJ, Wilson R, McKillop JH, Walker JJ (1991) Antioxidant systems in normal pregnancy and in pregnancy-induced hypertension. Am J Obstet Gynecol 165:1701–1704

    CAS  PubMed  Google Scholar 

  • Yang J, Boerm M, McCarty M, Bucana C, Fidler IJ, Zhuang Y, Su B (2000) Mekk3 is essential for early embryonic cardiovascular development. Nat Genet 24:309–313

    Article  CAS  PubMed  Google Scholar 

  • Yoshiki N, Kubota T, Aso T (2000) Expression and localization of heme oxygenase in human placental villi. Biochem Biophys Res Commun 276:1136–1142

    Article  CAS  PubMed  Google Scholar 

  • Zhang J, Dawson VL, Dawson TM, Snyder SH (1994) Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263:687–689

    CAS  PubMed  Google Scholar 

  • Zou MH, Leist M, Ullrich V (1999) Selective nitration of prostacyclin synthase and defective vasorelaxation in atherosclerotic bovine coronary arteries. Am J Pathol 154:1359–1365

    CAS  PubMed  Google Scholar 

  • Zulueta JJ, Yu FS, Hertig IA, Thannickal VJ, Hassoun PM (1995) Release of hydrogen peroxide in response to hypoxia-reoxygenation: role of an NAD(P)H oxidase-like enzyme in endothelial cell plasma membrane. Am J Respir Cell Mol Biol 12:41–49

    CAS  PubMed  Google Scholar 

  • Zusterzeel PL, Peters WH, De Bruyn MA, Knapen MF, Merkus HM, Steegers EA (1999) Glutathione S-transferase isoenzymes in decidua and placenta of preeclamptic pregnancies. Obstet Gynecol 94:1033–1038

    Article  CAS  PubMed  Google Scholar 

  • Zusterzeel PL, Rutten H, Roelofs HM, Peters WH, Steegers EA (2001a) Protein carbonyls in decidua and placenta of pre-eclamptic women as markers for oxidative stress. Placenta 22:213–219

    Article  CAS  PubMed  Google Scholar 

  • Zusterzeel PL, Wanten GJ, Peters WH, Merkus HM, Steegers EA (2001b) Neutrophil oxygen radical production in pre-eclampsia with HELLP syndrome. Eur J Obstet Gynecol Reprod Biol 99:213–218

    Article  CAS  PubMed  Google Scholar 

  • Zweier JL, Fertmann J, Wei G (2001) Nitric oxide and peroxynitrite in postischemic myocardium. Antioxid Redox Signal 3:11–22

    Article  CAS  PubMed  Google Scholar 

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  1. Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, PO Box 670526, Cincinnati, OH 45267-0526, USA

    Leslie Myatt & Xiaolan Cui

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  1. Leslie Myatt
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Correspondence to Leslie Myatt.

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Myatt, L., Cui, X. Oxidative stress in the placenta. Histochem Cell Biol 122, 369–382 (2004). https://doi.org/10.1007/s00418-004-0677-x

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