Thromboxane and Prostacyclin Production by Different Compartments of the Human Placental Villus*

Abstract

We separated the trophoblast and villous core of human placental villi to compare thromboxane (Tx) and prostacyclin production in these two compartments with eicosanoid production by intact villi. TxB2 and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolites of TxA2 and prostacyclin, respectively, were measured in serum-free media from 48-h incubations of intact villi, villous core tissue denuded of its trophoblast layer, and trophoblast cells. In villi, the medium TxB2 concentrations increased rapidly to a peak level of 20 +/- 9 (+/- SE) (n = 11) pg/microgram protein at 48 h; 6-keto-PGF1 alpha was first detected in medium at 20 h, and it increased to 19.6 +/- 4.0 pg/micrograms protein (n = 11) by 48 h. Compared to villi, villous core tissue denuded of its surface trophoblast layer had a 7-fold greater TxB2 level (136 +/- 17 pg/micrograms protein; n = 11) by 48 h, but a comparable level of 6-keto-PGF1 alpha (22.5 +/- 3.7 pg/micrograms protein). Trophoblast cultures produced predominantly TxB2 (109 +/- 18 pg/micrograms protein; n = 11) and had the lowest 6-keto-PGF1 alpha production among the three groups (11.4 +/- 2.6 pg/micrograms protein). At 48 h, the mean TxB2/6-keto-PGF1 alpha ratio was 1.0 in medium from intact villi, 6.2 in medium from villous core tissue, and 13.3 in medium from trophoblast cells. Indomethacin inhibited production of both eicosanoids in all cultures. Our studies indicate that intact placental villi produce equal amounts of Tx and prostacyclin, the trophoblast compartment produces predominantly Tx, and the villous core compartment produces an increased amount of Tx when denuded of its trophoblast layer. These data also suggest that the trophoblast produces an inhibitor or provides a catabolic function that limits villous core Tx production.

Predominant Basal Directional Release of Thromboxane, but not Prostacyclin, by Placental Trophoblasts from Normal and Preeclamptic Pregnancies

“…Placental trophoblasts produce a spectrum of vasoconstrictors and vasodilators including thromboxane (TX), angiotensin II (Ang II), endothelin, prostacyclin (PGI2), and NO (5)(6)(7). Maintaining a balance between these vasoconstrictors and vasodilators is critical to achieve a low resistance and high blood flow in the placental vasculature for proper placental growth and fetal development during pregnancy (8).…”

Contractility of Placental Vascular Smooth Muscle Cells in Response to Stimuli Produced by the Placenta: Roles of ACE vs. Non-ACE and AT1 vs. AT2 in Placental Vessel Cells

“…Placental tissues are not only able to produce various vasoactive agents, like angiotensin II (Ang II) [1][2][3], thromboxane (TX) [4][5][6], and endothelin (ET) [7,8], but also possess receptors for each of these vasoactivators, which ensure that the placental vasomotor activity is controlled in both the autocrine and/or the paracrine fashions. Using an organ bath perfusion model, we recently demonstrated that vasoconstrictors produced by preeclamptic placentas could induce constriction of chorionic plate arteries [9].…”

Altered release of endothelin‐1,2 and thromboxane B2 from trophoblastic cells in pre‐eclampsia

“…This is supported by a much greater cyclo-oxygenase content in cytotrophoblastic cells than in syncytial trophoblast [23]. This would also account for the pronounced decrease in TXB 2 production, also observed by others [23], after 24 h in culture in the presence of FCS, which favours syncytial formation, whereas in the absence of FCS TXB 2 levels remain virtually unchanged [18]. In addition, prostaglandin dehydrogenase levels are greater in syncytium than in cytotrophoblastic cells [25].…”

“…Obviously, the substances are formed from unknown sources in FCS. This would suggest that the cells should be cultured in serumfree media, but the cells would then lose their viability and metabolic activity after 24 h. This is why other studies in which trophoblastic cells were cultured in serum-free media were terminated after 48 h [18]. Therefore, the culture of cells in serum-free media would preclude the possibility of following the temporal changes in vasoactive substance levels and, therefore, was not a suitable option in the present investigation.…”

“…In normal pregnancies, isolated trophoblastic cells and placental arteries release primarily thromboxane A 2 [18] and prostacyclin [19] respectively. Leukotriene B 4 acts a vasoconstrictor in human placental cotyledons in vitro, but is less potent than thromboxane A 2 [20].…”