Indoleamine 2,3-dioxygenase: distribution and function in the developing human placenta

Studies in mice have suggested that the placenta is protected from immune rejection by maternal T cells by means of localised indoleamine 2,3-dioxygenase dependent depletion of tryptophan. To determine whether such mechanisms might operate in the human placenta, we have studied the physiological importance of human placental indoleamine 2,3-dioxygenase immunohistochemically and functionally. Indoleamine 2,3-dioxygenase is detectable immunohistochemically from day 6 human blastocysts and thereafter throughout pregnancy in syncytiotrophoblasts, extravillous cytotrophoblasts and macrophages in the villous stroma and in the fetal membranes. Interferon-gamma added to villous explants markedly stimulates indoleamine 2,3-dioxygenase protein expression in macrophages. Indoleamine 2,3-dioxygenase-mediated tryptophan degradation in the first trimester villous and decidual tissue explants is stimulated by interferon-gamma and inhibited by 1-methyl-tryptophan (an inhibitor of indoleamine 2,3-dioxygenase). Peripheral blood mononuclear cell proliferation is controlled by indoleamine 2,3-dioxygenase-mediated tryptophan degradation. These results suggest the cellular basis of a mechanism present at the human maternal-fetal interface involved in regulating the maternal immune response to conceptus.     

Expression of indoleamine 2,3-dioxygenase in the rhesus monkey and common marmoset

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step of tryptophan degradation along the kynurenine pathway, and is hypothesized to limit tryptophan availability at embryo implantation and prevent maternal T cell activation at the maternal–fetal interface. To determine if nonhuman primates are suitable models for investigating the role of IDO during pregnancy, we defined the expression of IDO in the rhesus monkey and common marmoset with particular attention to the female reproductive tract and placenta. IDO mRNA was detected by RT-PCR in the rhesus monkey term placenta, lung, small intestine, spleen, lymph node and nonpregnant uterus, and also in the common marmoset placenta. Immunohistochemical analysis of rhesus monkey tissues localized IDO to glandular epithelium of nonpregnant endometrium and first trimester decidua, vessel endothelium of nonpregnant myometrium, first trimester decidua and term decidua, and villous vessel endothelium and syncytiotrophoblast of term placenta. Western blot analysis confirmed IDO in rhesus monkey term placenta. In the common marmoset, IDO was detected in glandular epithelium of the nonpregnant uterus and in the decidua at day 60 and day 128 of gestation. IDO activity was higher in rhesus monkey and common marmoset decidua and placentas than in other tissues. Confirmation of IDO expression in rhesus monkey and common marmoset uterine and placental tissues supports the hypothesis that this enzyme regulates immune activation at the maternal–fetal interface and demonstrates that nonhuman primates may provide models with distinct similarities to human placentation to study the role of IDO in maternal–fetal immune dialogue.     

Expression of indoleamine 2,3-dioxygenase in the rhesus monkey and common marmoset

Indoleamine 2,3-dioxygenase (IDO) catalyzes the initial and rate-limiting step of tryptophan degradation along the kynurenine pathway, and is hypothesized to limit tryptophan availability at embryo implantation and prevent maternal T cell activation at the maternal-fetal interface. To determine if nonhuman primates are suitable models for investigating the role of IDO during pregnancy, we defined the expression of IDO in the rhesus monkey and common marmoset with particular attention to the female reproductive tract and placenta. IDO mRNA was detected by RT-PCR in the rhesus monkey term placenta, lung, small intestine, spleen, lymph node and nonpregnant uterus, and also in the common marmoset placenta. Immunohistochemical analysis of rhesus monkey tissues localized IDO to glandular epithelium of nonpregnant endometrium and first trimester decidua, vessel endothelium of nonpregnant myometrium, first trimester decidua and term decidua, and villous vessel endothelium and syncytiotrophoblast of term placenta. Western blot analysis confirmed IDO in rhesus monkey term placenta. In the common marmoset, IDO was detected in glandular epithelium of the nonpregnant uterus and in the decidua at day 60 and day 128 of gestation. IDO activity was higher in rhesus monkey and common marmoset decidua and placentas than in other tissues. Confirmation of IDO expression in rhesus monkey and common marmoset uterine and placental tissues supports the hypothesis that this enzyme regulates immune activation at the maternal-fetal interface and demonstrates that nonhuman primates may provide models with distinct similarities to human placentation to study the role of IDO in maternal-fetal immune dialogue.     

Maternal neutrophil apoptosis in normal pregnancy, preeclampsia, and normotensive intrauterine growth restriction.

OBJECTIVE: In normal pregnancy there is both a neutrophilia and a mild neutrophil activation. In preeclampsia both direct and indirect evidence supports further marked neutrophil activation. In the pathogenesis of preeclampsia peripheral blood neutrophils may play a vital role in communicating between the preeclamptic placenta and the maternal vascular endothelium and contribute to the endothelial cell dysfunction that characterizes the maternal syndrome of preeclampsia. Preeclampsia shares many elements with the systemic inflammatory response syndrome. Neutrophils, key effectors of the systemic inflammatory response syndrome, are associated with hepatic necrosis and adult respiratory distress syndrome, both of which most commonly kill women with preeclampsia. We hypothesized that delayed neutrophil apoptosis could explain (1) the neutrophilia of normal pregnancy and (2) the differential maternal responses to the shared placental abnormality of preeclampsia and normotensive intrauterine growth restriction. STUDY DESIGN: Neutrophils were isolated (dextran 500, Ficoll [Amersham Pharmacia Biotech AB, Uppsala, Sweden], and erythrocyte lysis) from (1) case patients with preeclampsia at 相似文献   

胎盘生长因子与子痫前期发病及一氧化氮关系的研究

目的:探讨胎盘生长因子(PLGF)在子痫前期发病中的作用及其与一氧化氮的关系。方法:选择妊娠期高血压疾病患者45例,其中妊娠期高血压10例,轻度子痫前期12例,重度23例;选择同期正常妊娠妇女20例作为对照组。采用免疫组织化学染色法和逆转录-聚合酶链式反应(RT-PCR)检测两组患者胎盘PLGF蛋白及mRNA的表达。采用硝酸盐还原酶法测定两组胎盘组织NO浓度的变化。结果:(1)免疫组化结果显示,轻度和重度子痫前期的胎盘绒毛合体滋养细胞、绒毛间质PLGF表达均显著低于正常妊娠组(P<0.05),妊娠期高血压组与正常组无差别;PLGF在妊娠期高血压、子痫前期组及正常妊娠组分布范围基本一致,主要分布在绒毛合体滋养细胞和间质细胞胞浆,部分血管合体膜上也有表达;(2)轻、重度子痫前期胎盘组织PLGF mRNA平均灰度分别为3.33±0.39、1.97±0.29,显著低于正常妊娠组的平均灰度4.87±0.60(P<0.01);(3)轻、重度子痫前期胎盘组织中NO浓度分别为8.20±5.56μmol/g、6.46±2.25μmol/g,显著低于对照组18.10±7.12μmol/g(P<0.05);妊娠期高血压组胎盘组织NO浓度与对照组差异无显著性;(4)胎盘组织中胎盘生长因子表达水平与胎盘组织NO浓度呈显著正相关(r=0.54,P<0.05)。结论:子痫前期胎盘组织中胎盘生长因子水平降低,NO浓度下降,可能在子痫前期的发病中起一定作用。     

Influence of maternal diabetes on placental fibroblast growth factor-2 expression, proliferation, and apoptosis

OBJECTIVE: Type I diabetes mellitus during pregnancy is associated with dysregulation of the oxygen and glucose metabolic pathways, both of which affect placental villous growth and function. Alteration of placental development in women with diabetes may contribute to the increased risk of preeclampsia, macrosomia, or fetal growth restriction. METHODS: To evaluate placental growth in the setting of maternal diabetes, immunohistochemical techniques were used to examine fibroblast growth factor-2 (FGF-2) expression, cell proliferation (Ki67), and apoptosis (Apo-Tag) in placentas from diabetic and nondiabetic patients. RESULTS: Immunostaining for FGF-2 in placentas from diabetic women demonstrated an increase in intensity within the villous stroma and syncytiotrophoblast (P<.05). Associated with these changes in FGF-2 expression, placentas from diabetic women showed no change in villous mitotic activity but did show decreased stromal compartment apoptosis. When expressed as a ratio of Ki67-positive:Apo-Tag-positive nuclei as an index of relative cell turnover, the stromal compartment showed a significant trend towards decreased nuclei turnover (P<.05), suggesting relative tissue growth in diabetic patients. CONCLUSION: Increased FGF-2 expression and decreased stromal cell compartment turnover in the diabetic placenta might be a compensatory mechanism in response to the altered physiologic milieu of maternal diabetes on placental function.     

Effects of vasoactive agents on intracellular calcium and force in myometrial and subcutaneous resistance arteries isolated from preeclamptic, pregnant, and nonpregnant woman

OBJECTIVE: Preeclampsia is a common and serious complication of pregnancy, characterized by maternal hypertension and proteinuria, placental insufficiency, and fetal growth restriction. The purpose of this study was to investigate whether intracellular Ca 2+ ([Ca 2+ ] i ) and contractile responses of vascular smooth muscle to vasoactive agents are altered in preeclampsia compared with normal pregnancy and the nonpregnant state. STUDY DESIGN: Subcutaneous and myometrial resistance arteries from women who had preeclampsia, normal pregnancy, and nonpregnant women were obtained at the time of cesarean section or hysterectomy. Arteries were mounted on an isometric myograph and loaded with the Ca 2+ indicator, fura-2AM, to permit simultaneous measurement of force and [Ca 2+ ] i . Reponses to endothelium-dependent relaxants (acetylcholine and substance P) and vasoconstrictors (depolarizing potassium solution, phenylephrine, and angiotensin II) were examined. RESULTS: The fall in [Ca 2+ ] i and relaxation in response to acetylcholine was significantly inhibited in both myometrial and subcutaneous arteries from preeclamptic women compared with arteries from nonpregnant or normal pregnant women. However, responses to substance P did not differ between the 3 groups. There were no significant differences in [Ca 2+ ] i or force responses to high potassium, phenylephrine, or angiotensin II in myometrial and subcutaneous resistance vessels in women with preeclampsia compared with normal pregnant women. However, force, but not [Ca 2+ ] i responses to angiotensin II, in subcutaneous vessels from normal pregnant and preeclamptic women were reduced compared with subcutaneous arteries from nonpregnant women, indicating that pregnancy is associated with a reduction in Ca 2+ sensitization in this tissue. A similar effect was not seen in myometrial arteries. CONCLUSION: Endothelial function is altered in preeclampsia, with loss of effect of acetylcholine, but not substance P. Vasoconstrictor reactivity is not increased in preeclampsia compared with uncomplicated normal pregnancy, and this is unlikely to be an explanation for the increased peripheral vascular resistance seen in preeclampsia.     

缺氧对重度子痫前期患者胎盘绒毛组织代谢足迹变化的影响

目的:探讨在不同氧浓度下体外培养正常妊娠孕妇及重度子痫前期患者胎盘绒毛组织培养液中代谢足迹的变化。方法:选择正常妊娠组(27例)及重度子痫前期组(27例)孕妇,在胎盘边缘、中间、近脐带处取绒毛组织,分别在1%氧浓度下及6%氧浓度下培养96小时,采用高效液相质谱色谱仪检测培养液中代谢产物,观察不同氧浓度下培养的绒毛组织代谢足迹的变化。结果:两组分别取自1%氧浓度和6%氧浓度下培养的同一胎盘边缘、中间、近脐带3点处胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05);1%氧浓度与6%氧浓度下培养的正常妊娠组胎盘绒毛组织代谢足迹比较,发现545个代谢物差异有统计学意义(P<0.05);1%氧浓度与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05),1%氧浓度下培养的正常妊娠组与6%氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P>0.05)。结论:缺氧可能影响胎盘绒毛组织的代谢,在重度子痫前期的发病机制中起重要作用,而利用高效液相质谱色谱仪的代谢组学技术能测定在不同氧浓度下培养的正常妊娠组和重度子痫前期孕妇胎盘绒毛组织代谢足迹的变化,表明该方法适合于重度子痫前期的代谢组学研究。     

Trophoblast debris modulates the expression of immune proteins in macrophages: a key to maternal tolerance of the fetal allograft?

Interactions between maternal immune cells and the placenta are of substantial interest since diseases of pregnancy, such as recurrent miscarriage, villitis of unknown etiology and preeclampsia may arise due to inadequate adaptation of the maternal immune system. During normal pregnancy trophoblast debris is shed from the placenta into the maternal blood in large quantities. This trophoblast debris is then rapidly cleared from the maternal circulation. In this study, we exposed trophoblast debris generated from an in vitro placental explant model to peripheral blood-derived macrophages and quantified a variety of molecules that are important in immune responses by ELISA or flow cytometry. Phagocytosis of trophoblast debris resulted in reduced cell-surface expression of MHC-II molecules, the costimulatory molecules (CD80, CD86, CD40 and B7H3), monocyte chemoattractant protein-1 (MCP-1), inter-cellular adhesion molecule 1 (ICAM-1) and IL-8 receptors in macrophages while the expression of programmed death-1 ligand 1 (PD-L1) was upregulated. In addition, phagocytosis of trophoblast debris induced the secretion of the anti-inflammatory cytokines IL-10, IL6 and IL1Ra and decreased the secretion of pro-inflammatory cytokines IL-1β, IL12p70 and IL-8 by macrophages. Phagocytosis of trophoblast debris also increased macrophage expression of the immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO). We have shown that phagocytosis of trophoblast debris from normal placentae alters the phenotype of macrophages such that they are likely to deviate maternal immune responses towards tolerance and away from inflammation. This may be one of the mechanisms that allow the human fetal allograft to survive in direct contact with the maternal immune system.     

Localisation of indoleamine 2,3-dioxygenase and kynurenine hydroxylase in the human placenta and decidua: implications for role of the kynurenine pathway in pregnancy

Indoleamine 2,3-dioxygenase (IDO) has been implicated in contributing to immunotolerance in early pregnancy, but the presence in the term placenta of mRNAs for enzymes that produce other biologically active kynurenine end-products suggests other functions for kynurenine pathway metabolites. The aim of this study was to investigate the localisation of two key enzymes - IDO and kynurenine hydroxylase (KYN-OHase) - in first trimester decidua and in the human placenta across pregnancy. Using immunocytochemistry, it was shown that there was strong expression of IDO and KYN-OHase in stromal and glandular epithelial cells of first trimester decidua. In first and second trimester placenta, IDO and KYN-OHase were localised to the syncytiotrophoblast, stroma and macrophages. IDO and KYN-OHase mRNAs were also identified, and the enzymes appear to be functional because kynurenine and 3-hydroxy-anthranilic acid (respective products of the activity of these enzyme) were released into the medium when first trimester placental explants were maintained in culture for 48h. In term placenta, both IDO and KYN-OHase immunoreactivities were confined mainly to vascular endothelial cells of villous blood vessels, and to macrophages within the fetal villus, whereas syncytial staining was very weak or absent. The shift of expression of these enzymes away from the syncytiotrophoblast to fetal endothelial cells in terminal villi suggests that the function of the enzymes may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy, to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation.     

Longitudinal serum concentrations of placental growth factor: evidence for abnormal placental angiogenesis in pathologic pregnancies

OBJECTIVE: Complicated pregnancies demonstrate abnormal decidual and placental villous vasculature. We examined maternal concentrations of vascular endothelial growth factor and placental growth factor in normal pregnancies and in pregnancies that were complicated by isolated idiopathic small-for-gestational-age (SGA) newborn infants, preeclampsia alone, or preeclampsia with SGA newborn infants at the time of clinical disease and before the onset of clinical signs. STUDY DESIGN: Serum vascular endothelial growth factor and placental growth factor were measured by enzyme-linked immunosorbent assay in cross-sectional and longitudinal cohorts of pregnant nulliparous women. The results were compared by Wilcoxon tests or a mixed-models method, respectively. RESULTS: In the cross-sectional study, serum placental growth factor was reduced in abnormal pregnancy relative to control subjects (SGA newborn infants, 18 [P =.04]; preeclampsia, 20; or preeclampsia with small- for-gestational-age newborn infants, 11 [P =.0001]) as early as 15 to 19 weeks of gestation in preeclampsia with SGA newborn infants. Vascular endothelial growth factor was <30 pg/mL in all serum specimens from pregnant women. CONCLUSION: We postulate that decreased placental growth factor production results in abnormalities of placental angiogenesis through direct and indirect effects on other vasculotropic growth factors.     

The effects of apoptotic, deported human placental trophoblast on macrophages: possible consequences for pregnancy

During pregnancy, trophoblasts are shed into maternal blood from the placenta as they die. Trophoblasts are fetal cells and are therefore immunologically foreign to the maternal immune system, but the effects of shed trophoblasts on the maternal immune system are poorly characterized. We have used an in vitro villous explant model to harvest shed trophoblasts. These shed trophoblasts consist of multinucleated syncytial knots as well as mononuclear cells, and approximately 90% are apoptotic as determined by immunostaining with antibodies recognizing activated caspase-3 and the M30 cytokeratin neoepitope. U937 cells phagocytosed the shed apoptotic trophoblasts and, subsequently, secretion of the anti-inflammatory cytokine IL-10 was increased. In contrast, secretion of the proinflammatory cytokine Il-1beta by U937 cells was decreased after phagocytosis of apoptotic trophoblasts and the changes in both IL-10 and IL-1beta secretion were blocked by co-incubation with the phagocytosis inhibitor cytochalasin B. Shed trophoblasts caused a significant increase also in expression of the, immunosuppressive, tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase. We speculate that the shedding of trophoblasts may not be simply a mechanism the fetus uses to dispose of aged trophoblasts but rather shed apoptotic trophoblasts may provide a chronic source of tolerizing paternally derived antigens to regulate maternal immune responses to the fetus.     

The effects of apoptotic,deported human placental trophoblast on macrophages: Possible consequences for pregnancy

During pregnancy, trophoblasts are shed into maternal blood from the placenta as they die. Trophoblasts are fetal cells and are therefore immunologically foreign to the maternal immune system, but the effects of shed trophoblasts on the maternal immune system are poorly characterized. We have used an in vitro villous explant model to harvest shed trophoblasts. These shed trophoblasts consist of multinucleated syncytial knots as well as mononuclear cells, and approximately 90% are apoptotic as determined by immunostaining with antibodies recognizing activated caspase-3 and the M30 cytokeratin neoepitope. U937 cells phagocytosed the shed apoptotic trophoblasts and, subsequently, secretion of the anti-inflammatory cytokine IL-10 was increased. In contrast, secretion of the proinflammatory cytokine Il-1β by U937 cells was decreased after phagocytosis of apoptotic trophoblasts and the changes in both IL-10 and IL-1β secretion were blocked by co-incubation with the phagocytosis inhibitor cytochalasin B. Shed trophoblasts caused a significant increase also in expression of the, immunosuppressive, tryptophan-metabolizing enzyme indoleamine 2,3-dioxygenase. We speculate that the shedding of trophoblasts may not be simply a mechanism the fetus uses to dispose of aged trophoblasts but rather shed apoptotic trophoblasts may provide a chronic source of tolerizing paternally derived antigens to regulate maternal immune responses to the fetus.     

Indoleamine 2,3-dioxygenase,immunosuppression and pregnancy

Pharmacologic inhibition of indoleamine 2,3-dioxygenase (IDO) activity during murine pregnancy results in maternal T-cell-mediated rejection of allogeneic but not syngeneic conceptuses. Increased risk of allogeneic pregnancy failure induced by exposure to IDO inhibitor is strongly correlated with maternal C3 deposition at the maternal-fetal interface. Here we review evidence that cells expressing IDO contribute to immunosuppression by inhibiting T-cell responses to tumor antigens and tissue allografts, as well as fetal tissues.     

Decreased killer cell activity in preeclampsia

Anti-D antibody-dependent cellular cytotoxicity of peripheral blood mononuclear cells was measured against O, Rh (D)-positive erythrocytes in 20 healthy pregnant women (chosen from all trimesters), and in 16 toxemic patients; it was then compared to the cytotoxic activities of 20 women 3 months after parturition and to that of 42 nonpregnant women. The application of an enzyme-like kinetic model for measurement of maximal cytotoxic function has permitted sensitive determination of the K cell function. It was found that during normal pregnancy maternal K cell activity did not change, whereas it was significantly decreased in preeclampsia.     

Calprotectin plasma level is elevated in preeclampsia

BACKGROUND: Calprotectin is a protein found in myelomonocytic cells and plays a role in various physiological functions such as inflammatory processes and antiproliferation of cells, and in the neutrophil defense against bacterial infections. Preeclampsia is characterized by maternal endothelial dysfunction and by insufficient trophoblast invasion into the maternal endometrium (decidua). In addition, preeclampsia is associated with maternal leukocyte activation and we therefore wanted to investigate whether calprotectin levels in plasma from women with preeclampsia differed from the levels in normotensive pregnant and nonpregnant women. METHOD: Calprotectin measurements were included in a case-control study of 20 preeclamptic women matched with 20 normotensive pregnant women regarding age, pregnancy length, parity and body mass index (BMI). We also measured calprotectin in 12 nonpregnant women. Calprotectin plasma levels were analyzed using an enzyme-linked immunosorbent assay (ELISA). RESULTS: We discovered significantly elevated plasma calprotectin levels in preeclamptic patients compared to matched normotensive pregnancies: 768 (612-1016) microg/L vs. 445 (276-598) microg/L (medians, 25, 75 percentiles, respectively), p = 0.002. CONCLUSIONS: The elevated plasma calprotectin levels demonstrated in the preeclampsia group supports the notion that leukocytes are activated in preeclampsia. The elevated calprotectin level might constitute a part of the innate defense in myelomonocytic cells against microorganisms in pregnancy. We suggest further elucidation of a role for calprotectin in the development of pregnancy disorders such as preeclampsia.     

Indoleamine 2,3-dioxygenase (IDO) expression in invasive extravillous trophoblast supports role of the enzyme for materno-fetal tolerance

It is still not understood how the fetus escapes from being attacked by the maternal immune system. Recent reports based on mouse and in vitro models have suggested that the enzyme indoleamine 2,3-dioxygenase (IDO) is important for materno-fetal tolerance. IDO activity in the human placenta is known to be high and might lead to inhibition of T-cell proliferation, thus preventing fetal tissue from rejection by the maternal immune system. In an attempt to elucidate the precise location of IDO at the feto-maternal junctional zone, we investigated human placental and decidual tissue of first and third trimester of pregnancy using an immunohistochemical approach. In placental tissues, only syncytiotrophoblast and endothelial cells showed moderate expression of IDO. This pattern was observed regardless of whether first or third trimester tissue was investigated. In early and term decidua, cells with the typical morphology of invasive extravillous trophoblast (EVT) were strongly positive for IDO. Blocking immunohistochemical experiments with cytokeratin and IDO antibodies identified invasive EVT as the location of predominant IDO expression. Since EVT are the fetal cells with the closest contact to the maternal immune system, our results suggest that it is EVT which protects the fetus from rejection by downregulating local maternal T-cell responses.     

绒毛及合体滋养层细胞吲哚胺2,3-二氧化酶表达与流产的关系

目的:探讨人早孕绒毛组织吲哚胺2,3-二氧化酶(IDO)的表达与流产的关系。方法:RT-PCR测正常妊娠和难免流产绒毛组织及JAR细胞株IDOmRNA表达;免疫组化分析两组绒毛组织IDO蛋白质表达;Westernblot检测体外培养的合体滋养层细胞IDO蛋白质表达;高效液相色谱法检测细胞培养上清液中有无犬尿氨酸。结果:难免流产组绒毛组织IDOmRNA及蛋白质表达均低于正常组;JAR细胞株不表达IDOmRNA;合体滋养层细胞表达IDO蛋白质;合体滋养层细胞培养上清中有犬尿氨酸。结论:绒毛组织IDO正常表达是维持妊娠所必需;体外培养的人早孕绒毛合体滋养层细胞表达的IDO具有活性。     

Placental and serum levels of carotenoids in preeclampsia

OBJECTIVE: We compared placental tissue, maternal serum, and umbilical cord venous blood levels of four dietary carotenoids (alpha-carotene, beta-carotene, lycopene, and canthaxanthin) in normal pregnant women and those with preeclampsia. METHODS: Levels of alpha-carotene, beta-carotene, lycopene, and canthaxanthin were measured in placental tissue, maternal serum, and umbilical cord venous blood from 22 normal pregnant women and 19 women with preeclampsia. The criteria for recruitment included gestational age of 30-42 weeks, singleton pregnancy, intact membranes, absence of labor contractions, and absence of any other medical complication concurrent with preeclampsia. Carotenoids were measured using high-pressure liquid chromatography. RESULTS: All four carotenoids were detectable in human placental tissue, maternal serum, and umbilical cord venous blood samples. The levels of beta-carotene, lycopene, and canthaxanthin in placentas from preeclamptic women were significantly lower (P =.032, .009, and .013, respectively, by Mann-Whitney test) than those from normal pregnant women. Maternal serum levels of beta-carotene and lycopene were significantly lower (P =.004 and .008, respectively, by Mann-Whitney test) in women with preeclampsia. However, umbilical cord venous blood levels of these carotenoids were not significantly different between the two groups. CONCLUSION: Lower placental tissue and maternal serum carotenoid levels in women with preeclampsia suggest that oxidative stress or a dietary antioxidant influence might have an effect on the pathophysiology of preeclampsia.