Eicosanoid biosynthetic enzymes in placental and decidual tissues from preeclamptic pregnancies: increased expression of thromboxane-A2 synthase gene.

Woodworth, Steven H.; Li, X; Lei, Z M; Rao, Ch.V.; Yussman, Marvin A.; Spinnato, Joseph A.; Yokoyama, Chieko; Tanabe, Tadashi; Ullrich, Volker

doi:10.1210/jcem.78.5.8175982

Cited by 19 publications

(10 citation statements)

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“…Importantly, TX levels are elevated in the serum (12,42) and placental villi (8,11) of women with preeclampsia. Consistent with this observation, the expression of cyclooxygenase-2 (8, 21) and TX synthase (43) are enhanced in placental villi from women with preeclampsia. Because apoptosis is more prevalent in placentas from pregnancies complicated by FGR (7) or preeclampsia (44), it is possible that TX enhances apoptosis in these pregnancy-related diseases.…”

Section: Thromboxane Effect On Human Trophoblastssupporting

confidence: 72%

Thromboxane A2 Limits Differentiation and Enhances Apoptosis of Cultured Human Trophoblasts

et al. 2001

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Prostanoids influence differentiation in diverse cell types. Altered expression of cyclooxygenase and prostaglandins has been implicated in the pathophysiology of placental dysfunction, which results in preeclampsia and fetal growth restriction. We hypothesized that prostanoids modulate differentiation and apoptosis in cultured human trophoblasts. Villous cytotrophoblasts were isolated from term human placentas and cultured in serumfree medium. The level of human chorionic gonadotropin was used as a marker of biochemical differentiation of primary trophoblasts, and syncytia formation was used as a marker of morphologic differentiation. Of the prostanoids tested, we found exposure to thromboxane A 2 hindered both biochemical and morphologic differentiation of cultured trophoblasts. As expected, human chorionic gonadotropin levels in the media were elevated in a concentration-dependent manner in the presence of the thromboxane synthase inhibitor, sodium furegrelate, or the thromboxane A 2 receptor blocker SQ 29,548. Furthermore, thromboxane A 2 enhanced trophoblast apoptosis, determined using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, cell morphology, and a concentrationdependent increase in p53 expression. We conclude that thromboxane A 2 hinders differentiation and enhances apoptosis in cultured trophoblasts from term human placenta. We speculate that thromboxane may contribute to placental dysfunction by restricting differentiation and enhancing apoptosis in human trophoblasts. The function of the human placenta depends on multinucleated, terminally differentiated syncytiotrophoblasts. This epithelium is in direct contact with maternal blood and regulates maternal-fetal exchange of micronutrients and gases. The syncytiotrophoblast arises from fusion of relatively undifferentiated, mitotically active cytotrophoblasts. This process involves morphologic and biochemical differentiation. Morphologic differentiation is defined by fusion of mononucleated cytotrophoblasts with adjacent syncytium (1). Biochemical differentiation is characterized by production of hormones such as hCG and human placental lactogen (2-4). Preeclampsia and FGR are associated with trophoblast hypoxia and placental dysfunction (5). Villi from women with these conditions typically exhibit diminished villus formation, prominent cytotrophoblasts, enhanced syncytial knot formation, and apoptosis (6, 7). An increase in TX synthesis has been demonstrated in villi (8, 9) and trophoblasts (10, 11) from preeclamptic women compared with healthy control subjects. Importantly, FGR (12) and preeclampsia (13) are associated with elevated TXA 2 levels in the circulation of pregnant women. Although the effect of prostanoids on vascular reactivity is well known (14), recent studies indicate that prostanoids also regulate proliferation, differentiation, and apoptosis in many cell types (15-18). We tested the hypothesis that prostanoids influence the differentiation of cultured trophoblasts from term human placenta. We found ...

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Section: Thromboxane Effect On Human Trophoblastssupporting

confidence: 72%

Thromboxane A2 Limits Differentiation and Enhances Apoptosis of Cultured Human Trophoblasts

et al. 2001

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“…10) In villi and deciduas, no Gene PLA 2 Forward 5Ј-GAC TGG AGA GCC ACC CTG AAG Reverse 5Ј-CGG CGT TCA GGT ACG TGT C COX-2 Forward 5Ј-GCG AGG GCC AGC TTT CA Reverse 5Ј-CAG AGT TTC ACC GTA AAT ATG ATT TAA PGI 2 Forward 5Ј-CCA CGC ACC CAT GAA AGC synthase Reverse 5Ј-TGG CGA AAG GTG TGG AAG A differences in COX-1 and COX-2 expression were found between normal and PIH pregnant groups, but the TXA 2 synthase content was increased in the PIH pregnant group. 11) In the present study, the existence of COX-2 in normal and PIH placental tissues became clear as a result of immunohistochemical staining. However, there was no difference for COX-2 staining.…”

Section: Discussionsupporting

confidence: 59%

Examination of the Expression of Cyclooxygenase-2 in Placenta Villi from Sufferers of Pregnancy Induced Hypertension

Okawara

Matsuoka

Hashimoto

et al. 2009

Biological & Pharmaceutical Bulletin

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Pregnancy induced hypertension (PIH) causes hypertensive cerebropathy, deep vein thrombosis, pulmonary embolismlung edema, intrauterine growth retardation, and premature delivery. It is therefore considered to be a serious disease that affects both mother and fetus. However, the mechanism through which PIH induces its clinical symptoms is unknown. At first, damage to vascular endothelial cells induces vasoconstriction and hemoconcentration, resulting in fetoplacental circulation dysfunction. Then, clinical symptoms such as hypertension and protein urea are induced.As described above, the damage caused to vascular endothelial cells is the main pathogenic factor in PIH and results in decreased concentrations of vasodilatatory factors. Therefore, it is assumed that circulation homeostasis is disrupted. The prostaglandin I 2 (PGI 2 )-thromboxane A 2 (TXA 2 ) adjustment system is present in many circulation control systems. Prostaglandin I 2 is synthesized in the endovascular system and acts as a vasodilator in addition to its inhibitory effect on platelet aggregation. In contrast, TXA 2 is synthesized by platelets, acts as a vasoconstrictor, and induces platelet aggregation. Furthermore, PGI 2 and TXA 2 are synthesized from the same precursor, arachidonic acid. These prostaglandins, which have opposite effects, are synthesized in close proximity to each other, such as in blood vessels and platelets, and maintain circulation homeostasis. Therefore, the PGI 2 -TXA 2 balance is considered to be a complex mechanism for circulation control. Additionally, PGI 2 and TXA 2 are synthesized in the placenta, umbilical vein, uterine blood vessel, amnion, chorionic villi, and decidua. The PGI 2 -TXA 2 balance is considered to be very important in the fetoplacental circulating system; therefore, an imbalance in this system may play an important part in PIH pathogenesis.1) In another report, production of PGI 2 was decreased and TXA 2 was increased in the blood, urine, and tissues of PIH maternal and fetal tissues, indicating that the PGI 2 -TXA 2 equilibrium in these tissues is pushed towards TXA 2 . Similar results have also been reported in umbilical and placental tissue.2) These differences may depend on (1) the activity of prostaglandin production enzymes, (2) the content of these enzymes, and (3) the activity of inhibitors for these enzymes.Satoh et al. reported that the activity of enzymes such as cyclooxygenase-2 (COX-2), which takes part in the synthesis of PGI 2 , is decreased in the endothelium of the umbilical vein in patients with severe PIH, resulting in an imbalance in the PGI 2 -TXA 2 system that leads to TXA 2 predominance. 3)However, in their report, no distinction between COX-1 and COX-2 was made because the isozymes of COX had not yet been discovered. In addition, Keirse et al. determined the contents of COX and PGI 2 synthetase using an immunoradiometric assay with monoclonal antibody. 4,5) In their report, COX was induced and increased with increasing gestational age, but there was no difference in the level ...

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“…Increased expression of COX-2 appears to be wide spread. COX-2 is increased in placentas of women with preeclampsia where its expression is related to increased production of thromboxane24, 25. Placentas obtained from preeclamptic women produce more thromboxane and less prostacyclin than placentas obtained from normal pregnant women26.…”

Section: Discussionmentioning

confidence: 99%

Neutrophil Expression of Cyclooxygenase 2 in Preeclampsia

2010

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The objective of this study was to determine: 1) if neutrophils of preeclamptic women express cyclooxygenase-2 (COX-2), and 2) if COX-2 mediates neutrophil interleukin-8 (IL-8) production. Neutrophils were isolated from heparinized blood collected from women with preeclampsia and normal pregnancy, and from normal nonpregnant women. COX-2 protein was measured in the neutrophils of the three groups by specific ELISA. To study the role of COX-2 in IL-8 production, neutrophils of normal pregnant women were activated with arachidonic acid and incubated overnight in Medium 199 with and without NS398, a specific COX-2 inhibitor. We found that neutrophils from preeclamptic women expressed significantly more COX-2 than neutrophils from normal pregnant or normal nonpregnant women. Arachidonic acid activated neutrophils to produce IL-8 which was completely inhibited by NS398. These data demonstrate that COX-2 is expressed in neutrophils of preeclamptic women and that COX-2 mediates IL-8 production by activated neutrophils.

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Eicosanoid biosynthetic enzymes in placental and decidual tissues from preeclamptic pregnancies: increased expression of thromboxane-A2 synthase gene.

Cited by 19 publications

References 0 publications

Thromboxane A2 Limits Differentiation and Enhances Apoptosis of Cultured Human Trophoblasts

Thromboxane A2 Limits Differentiation and Enhances Apoptosis of Cultured Human Trophoblasts

Examination of the Expression of Cyclooxygenase-2 in Placenta Villi from Sufferers of Pregnancy Induced Hypertension

Neutrophil Expression of Cyclooxygenase 2 in Preeclampsia

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