In vitro approaches to evaluate placental drug transport by using differentiating JEG-3 human choriocarcinoma cells. Ikeda Kenji,Utoguchi Naoki,Tsutsui Hidenobu,Yamaue Satoko,Homemoto Manami,Nakao Erina,Hukunaga Yumi,Yamasaki Kyohei,Myotoku Michiaki,Hirotani Yoshihiko Basic & clinical pharmacology & toxicology Human choriocarcinoma cells have been used as models for studying transcellular drug transport through placental trophoblasts. However, these models allow the transport of low-molecular-weight drugs through intercellular gap junctions. This study aimed at investigating the differentiation patterns of JEG-3 choriocarcinoma cells under different culture conditions and establishing the appropriate model of in vitro syncytiotrophoblast drug transport. Paracellular permeability was estimated by measuring the transepithelial electrical resistance (TEER) across JEG-3 cell layers. The mRNA expression levels of non-expressed in choriocarcinoma clone 1 (NECC1) and breast cancer resistance protein (BCRP), and those of E-cadherin (ECAD) and cadherin-11 (CDH11), which are adherens junction-associated proteins related to fusogenic ability of syncytiotrophoblasts differentiated from cytotrophoblasts, protein expression levels were considered as the differentiation signals. The highest TEER values were obtained in the JEG-3 cells cultured in the Dulbecco's modified Eagle's medium (DMEM)/Ham's F-12 (1:1) mixed medium (CS-C(®) ; Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan). By comparing the TEER values and the differentiation signals, the authors identified at least five JEG-3 cell-differentiation patterns. The differentiation pattern of JEG-3 cultured in CS-C resembled the syncytiotrophoblast-like differentiation signal characterizations in vivo. In conclusion, the syncytiotrophoblast-like models of differentiating JEG-3 cells cultured in CS-C might be appropriate for evaluating drug transport across the placental trophoblast. 10.1111/j.1742-7843.2010.00634.x

Magnesium sulfate attenuates peroxide-induced vasoconstriction in the human placenta. Walsh S W,Romney A D,Wang Y,Walsh M D American journal of obstetrics and gynecology OBJECTIVE:Magnesium sulfate is used to prevent convulsions in preeclamptic women. It acts as a calcium antagonist but may also stimulate prostacyclin. Because magnesium sulfate readily crosses the placenta, we evaluated whether it might have a beneficial effect on placental blood flow. STUDY DESIGN:Isolated human placental cotyledons (n = 6) were perfused for 20-minute intervals with control Krebs-Ringer-bicarbonate buffer, 200 mumol/L t-butyl hydroperoxide, magnesium sulfate (6 mEq/L), peroxide plus magnesium sulfate, and peroxide plus magnesium sulfate plus calcium chloride (6.25 mEq/L). Peroxide perfusion was used to stimulate thromboxane to induce vasoconstriction. Fetal perfusion pressure was continually monitored. Maternal and fetal effluent samples were analyzed for thromboxane and prostacyclin by their stable metabolites, thromboxane B2 and 6-keto-prostaglandin F1 alpha. RESULTS:Compared with control Krebs-Ringer-bicarbonate buffer perfusion, peroxide perfusion significantly increased (p < 0.05) vascular resistance (12.9 +/- 1.2 vs 21.1 +/- 2.6 mm Hg.min/ml, mean +/- SE) and thromboxane B2 secretion (fetal -0.22 +/- 0.08 vs 0.73 +/- 0.11 ng/min, maternal -1.5 +/- 0.4 vs 4.4 +/- 0.7 ng/min). Subsequent perfusion with magnesium sulfate significantly attenuated (p < 0.05) peroxide-induced vasoconstriction (15.1 +/- 1.7 mm Hg.min/ml), which was reversed by the addition of calcium (19.7 +/- 2.2 mm Hg.min/ml). Magnesium sulfate partially, but significantly (p < 0.05), inhibited the peroxide-induced increase in maternal thromboxane B2 secretion (3.2 +/- 0.6 ng/min) but not fetal thromboxane B2 secretion (1.1 +/- 0.3 ng/min). Magnesium sulfate did not affect 6-keto-prostaglandin F1 alpha secretion. CONCLUSIONS:(1) Magnesium sulfate attenuates peroxide-induced vasoconstriction in the human placenta. (2) This effect is mediated by inhibition of thromboxane synthesis and antagonism of calcium. 10.1016/s0002-9378(98)70618-0