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Increased placental progesterone may cause decreased placental prostacyclin production in preeclampsia
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Citations from the Literature
study the effect high glucose levels can have on human fetal cell proliferation in vitro. Cells were subcultured in a modified minimum essential medium with 10% fetal bovine serum containing either 5.5 mmol/L (100 mg/dl) D-glucose (control), 11 mmol/L (200 mg/dl) D-glucose, or 22 mhol/L (400 mg/dl) Dglucose. Cells grown in mannitol-containing media were used as controls for osmolality. After 3 and 7 days’ growth in different media, the labeling index was determined by autoradiographic analysis, and cell numbers were determined with a Coulter counter. The labeling indices for cells grown 3 days in 11 or 22 mmol/L D-glucose were 89% (p < 0.002) and 84% (p < O.OOl), respectively, of control cells grown in 5.5 mmol/L Dglucose. After 7 days’ growth, the labeling indices of cells grown in 11 or 22 mmol/L D-glucose were 84% (p < 0.002) and 70% (p < O.OOl),respectively, of cells grown in 5.5 mmol/ L D-glucose media. There was a significant decrease in the number of cells present at both 3 and 7 days in cultures grown in 22 mmol/L D-glucose compared with control. We conclude that a few day’s exposure to high glucose levels can have an effect on proliferation of human placental cells in vitro. We suggest that a glucose effect on proliferation of other cells derived from the products of conception might be one mechanism contributing to abnormal development in some pregnancies of diabetic women. Prostaglsndin E, metabolism in the human fetal membranes Cheung PYC; Challis JRG Department of Obstetrics and Gynecology, University of Western Ontario, 268 Grosvenor St., London, Ont. N6A 4V2, CAN
AM J OBSTET GYNECOL 1989,161/6 1(1580-1585) Prostaglandins play a pivotal role in the initiation and maintenance of labor, but the sources that contribute to the production of primary prostaglandins (prostaglandin E, and prostaglandin F(2a)) remain controversial. In decidua, prostaglandin F(2a) may be formed de novo or from prostaglandin E, through 9-ketoreductase activity, although it has been suggested that metabolism to 13,14-dihydro-15-ketoprostaglandin E, through 15-hydroxyprostaglandin dehydrogenase is dominant. To examine this possibility, and to determine changes with labor, we examined interconversions of prostaglandin E, to prostaglandin F(2o), 13,lCdihydro-15-ketoprostaglandin E, and 13,14-dihydro-15-ketoprostaglandin F(2m) by dispersed cells of decidua, chorion, and amnion obtained from patients at term elective cesarean section or after spontaneous labor. Incubations were performed with increasing concentrations (1 to 100 ng/ml) of prostaglandin E, for 2 and 4 h, and products were measured by radioimmunoassay. The 13,14-dihydro-15ketoprostaglandin E, was measured as ll-deoxy-13, lCdihydro-15keto-1 lfi,l6psi-cycloprostaglandin E,. Basal output of prostaglandin E, increased between cesarean section and spontaneous labor from 190.6 f 109 pg/105 cells (2 SE) to 605.2 f 346.8 in amnion, nondetectable to 24.5 + 11.2 in chorion, and 18 f 16 to 69 f 25.8 in decidua. For both cesarean section and spontaneous labor patients there was very little con-
Int J Gynecol Obstet 33
version of prostaglandin E, by the amnion, substantial conversion to 13,14-dihydro-15-ketoprostaglandin E, by the chorion, and some conversion to 13,14-dihydro-15-ketoprostaglandin E* by the decidua. Percentage conversions did not change with labor. Prostaglandin F(2a) was formed by all tissues but only in trace amounts. All tissues from one cesarean section patient showed substantial conversion of prostaglandin E, to prostaglandin F(2a), but very little 13,14-dihydro-15ketoprostaglandin E, or 13,14-dihydro-15-ketoprostaglandin F(2o) formation, indicating either a decrease or deficiency in the 15-hydroxyprostaglandin dehydrogenase activity. We conclude that conversion of exogenous prostaglandin E, to prostaglandin F(2a) can occur in intrauterine tissues, but this does not normally contribute significantly to the prostaglandin F(2a) output by the human decidua and fetal membranes.
Increased placental progesterone may cause decreased placental prostacyclin production in preeclampsia Walsh SW; Coulter S Department of Physiology and Cell Biology, Texas Medical School, Houston, TX, USA
University of
AM J OBSTET GYNECOL 1989,161/6 1(1586-1592) Placentas obtained from women with preeclampsia produce more thromboxane and less prostacyclin than normal. They also produce more progesterone than normal. This study tested whether a progesterone concentration equivalent to that in the medium after in vitro incubation of placentas from women with preeclampsia (2 I .5 x lo-’ mol/L) could cause an imbalance of increased thromboxane and decreased prostacyclin production by normal placentas. Fresh term placental tissues were incubated for 48 hours in the absence or presence of various concentrations of progesterone and/or estradiol. Prostacyclin and determined by thromboxane were radioimmunoassay of their stable metabolites, 6-keto-prostaglandin F(la) and thromboxane B,. A progesterone concentration of 1.5 x 10m5mol/L significantly (p < 0.001) inhibited prostacyclin production, compared with control, but lower concentrations did not. Estradiol at concentrations present in the medium after incubation of either normal or preeclamptic placental tissue did not significantly affect prostacyclin production, nor did it prevent progesterone at 1.5 x lo-’ mol/L from inhibiting prostacyclin. Thromboxane production was not affected by either progesterone or estradiol. Conclusion: In vitro addition of progesterone at a concentration equivalent to that in the medium after incubation of preeclamptic placentas inhibited prostacyclin production by normal placentas to a rate characteristic of preeclampsia. However, it did not increase thromboxane. Speculation: Increased trophoblast progesterone in preeclampsia may act by a paracrine mechanism to inhibit prostacyclin synthesis in placental vasculature. Progesterone’s selective inhibition of prostacyclin without affecting thromboxane may be due to the compartmentalization of thromboxane production to trophoblast and stroma and prostacyclin production to placental vasculature.
Citations from the Literature
study the effect high glucose levels can have on human fetal cell proliferation in vitro. Cells were subcultured in a modified minimum essential medium with 10% fetal bovine serum containing either 5.5 mmol/L (100 mg/dl) D-glucose (control), 11 mmol/L (200 mg/dl) D-glucose, or 22 mhol/L (400 mg/dl) Dglucose. Cells grown in mannitol-containing media were used as controls for osmolality. After 3 and 7 days’ growth in different media, the labeling index was determined by autoradiographic analysis, and cell numbers were determined with a Coulter counter. The labeling indices for cells grown 3 days in 11 or 22 mmol/L D-glucose were 89% (p < 0.002) and 84% (p < O.OOl), respectively, of control cells grown in 5.5 mmol/L Dglucose. After 7 days’ growth, the labeling indices of cells grown in 11 or 22 mmol/L D-glucose were 84% (p < 0.002) and 70% (p < O.OOl),respectively, of cells grown in 5.5 mmol/ L D-glucose media. There was a significant decrease in the number of cells present at both 3 and 7 days in cultures grown in 22 mmol/L D-glucose compared with control. We conclude that a few day’s exposure to high glucose levels can have an effect on proliferation of human placental cells in vitro. We suggest that a glucose effect on proliferation of other cells derived from the products of conception might be one mechanism contributing to abnormal development in some pregnancies of diabetic women. Prostaglsndin E, metabolism in the human fetal membranes Cheung PYC; Challis JRG Department of Obstetrics and Gynecology, University of Western Ontario, 268 Grosvenor St., London, Ont. N6A 4V2, CAN
AM J OBSTET GYNECOL 1989,161/6 1(1580-1585) Prostaglandins play a pivotal role in the initiation and maintenance of labor, but the sources that contribute to the production of primary prostaglandins (prostaglandin E, and prostaglandin F(2a)) remain controversial. In decidua, prostaglandin F(2a) may be formed de novo or from prostaglandin E, through 9-ketoreductase activity, although it has been suggested that metabolism to 13,14-dihydro-15-ketoprostaglandin E, through 15-hydroxyprostaglandin dehydrogenase is dominant. To examine this possibility, and to determine changes with labor, we examined interconversions of prostaglandin E, to prostaglandin F(2o), 13,lCdihydro-15-ketoprostaglandin E, and 13,14-dihydro-15-ketoprostaglandin F(2m) by dispersed cells of decidua, chorion, and amnion obtained from patients at term elective cesarean section or after spontaneous labor. Incubations were performed with increasing concentrations (1 to 100 ng/ml) of prostaglandin E, for 2 and 4 h, and products were measured by radioimmunoassay. The 13,14-dihydro-15ketoprostaglandin E, was measured as ll-deoxy-13, lCdihydro-15keto-1 lfi,l6psi-cycloprostaglandin E,. Basal output of prostaglandin E, increased between cesarean section and spontaneous labor from 190.6 f 109 pg/105 cells (2 SE) to 605.2 f 346.8 in amnion, nondetectable to 24.5 + 11.2 in chorion, and 18 f 16 to 69 f 25.8 in decidua. For both cesarean section and spontaneous labor patients there was very little con-
Int J Gynecol Obstet 33
version of prostaglandin E, by the amnion, substantial conversion to 13,14-dihydro-15-ketoprostaglandin E, by the chorion, and some conversion to 13,14-dihydro-15-ketoprostaglandin E* by the decidua. Percentage conversions did not change with labor. Prostaglandin F(2a) was formed by all tissues but only in trace amounts. All tissues from one cesarean section patient showed substantial conversion of prostaglandin E, to prostaglandin F(2a), but very little 13,14-dihydro-15ketoprostaglandin E, or 13,14-dihydro-15-ketoprostaglandin F(2o) formation, indicating either a decrease or deficiency in the 15-hydroxyprostaglandin dehydrogenase activity. We conclude that conversion of exogenous prostaglandin E, to prostaglandin F(2a) can occur in intrauterine tissues, but this does not normally contribute significantly to the prostaglandin F(2a) output by the human decidua and fetal membranes.
Increased placental progesterone may cause decreased placental prostacyclin production in preeclampsia Walsh SW; Coulter S Department of Physiology and Cell Biology, Texas Medical School, Houston, TX, USA
University of
AM J OBSTET GYNECOL 1989,161/6 1(1586-1592) Placentas obtained from women with preeclampsia produce more thromboxane and less prostacyclin than normal. They also produce more progesterone than normal. This study tested whether a progesterone concentration equivalent to that in the medium after in vitro incubation of placentas from women with preeclampsia (2 I .5 x lo-’ mol/L) could cause an imbalance of increased thromboxane and decreased prostacyclin production by normal placentas. Fresh term placental tissues were incubated for 48 hours in the absence or presence of various concentrations of progesterone and/or estradiol. Prostacyclin and determined by thromboxane were radioimmunoassay of their stable metabolites, 6-keto-prostaglandin F(la) and thromboxane B,. A progesterone concentration of 1.5 x 10m5mol/L significantly (p < 0.001) inhibited prostacyclin production, compared with control, but lower concentrations did not. Estradiol at concentrations present in the medium after incubation of either normal or preeclamptic placental tissue did not significantly affect prostacyclin production, nor did it prevent progesterone at 1.5 x lo-’ mol/L from inhibiting prostacyclin. Thromboxane production was not affected by either progesterone or estradiol. Conclusion: In vitro addition of progesterone at a concentration equivalent to that in the medium after incubation of preeclamptic placentas inhibited prostacyclin production by normal placentas to a rate characteristic of preeclampsia. However, it did not increase thromboxane. Speculation: Increased trophoblast progesterone in preeclampsia may act by a paracrine mechanism to inhibit prostacyclin synthesis in placental vasculature. Progesterone’s selective inhibition of prostacyclin without affecting thromboxane may be due to the compartmentalization of thromboxane production to trophoblast and stroma and prostacyclin production to placental vasculature.