Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon; and Center for Developmental Health, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon
Division of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon; and.
Am J Physiol Regul Integr Comp Physiol. 2014 Aug 1;307(3):R354-60. doi: 10.1152/ajpregu.00070.2014. Epub 2014 Jun 4.
We hypothesized that prostaglandin E2 (PGE2) stimulates amniotic fluid transport across the amnion by upregulating vascular endothelial growth factor (VEGF) expression in amnion cells and that amniotic PGE2 concentration correlates positively with intramembranous (IM) absorption rate in fetal sheep. The effects of PGE2 at a range of concentrations on VEGF 164 and caveolin-1 gene expressions were analyzed in cultured ovine amnion cells. IM absorption rate, amniotic fluid (AF) volume, and PGE2 concentration in AF were determined in late-gestation fetal sheep during control conditions, isovolumic fetal urine replacement (low IM absorption rate), or intra-amniotic fluid infusion (high IM absorption rate). In ovine amnion cells, PGE2 induced dose- and time-dependent increases in VEGF 164 mRNA levels and reduced caveolin-1 mRNA and protein levels. VEGF receptor blockade abolished the caveolin-1 response, while minimally affecting the VEGF response to PGE2. In sheep fetuses, urine replacement reduced amniotic PGE2 concentration by 58%, decreased IM absorption rate by half, and doubled AF volume (P < 0.01). Intra-amniotic fluid infusion increased IM absorption rate and AF volume (P < 0.01), while amniotic PGE2 concentration was unchanged. Neither IM absorption rate nor AF volume correlated with amniotic PGE2 concentration under each experimental condition. Although PGE2 at micromolar concentrations induced dose-dependent responses in VEGF and caveolin-1 gene expression in cultured amnion cells consistent with a role of PGE2 in activating VEGF to mediate AF transport across the amnion, amniotic PGE2 at physiological nanomolar concentrations does not appear to regulate IM absorption rate or AF volume.
我们假设前列腺素 E2（PGE2）通过上调羊膜细胞中血管内皮生长因子（VEGF）的表达来刺激羊水穿过羊膜的转运，并且羊膜中的 PGE2 浓度与胎儿羊膜内（IM）吸收率呈正相关。分析了一系列浓度的 PGE2 对培养的绵羊羊膜细胞中 VEGF164 和 caveolin-1 基因表达的影响。在控制条件下、等容胎儿尿液替代（低 IM 吸收率）或羊膜内液体输注（高 IM 吸收率）期间，测定晚期妊娠胎儿羊的 IM 吸收率、羊水（AF）量和 AF 中的 PGE2 浓度。在绵羊羊膜细胞中，PGE2 诱导 VEGF164 mRNA 水平的剂量和时间依赖性增加，并降低 caveolin-1 mRNA 和蛋白水平。VEGF 受体阻断消除了 caveolin-1 反应，而对 PGE2 对 VEGF 的反应影响最小。在绵羊胎儿中，尿液替代使羊膜 PGE2 浓度降低 58%，IM 吸收率减半，AF 量增加一倍（P<0.01）。羊膜内液体输注增加了 IM 吸收率和 AF 量（P<0.01），而羊膜 PGE2 浓度不变。在每种实验条件下，IM 吸收率或 AF 量均与羊膜 PGE2 浓度无关。尽管在培养的羊膜细胞中，PGE2 在微摩尔浓度下诱导 VEGF 和 caveolin-1 基因表达的剂量依赖性反应，与 PGE2 激活 VEGF 以介导羊水穿过羊膜的转运作用一致，但生理纳摩尔浓度的羊膜 PGE2 似乎不调节 IM 吸收率或 AF 量。
