Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta
Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta
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DOI：
10.1016/s0002-9378(99)70661-7
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发表时间：
1999-04-01
影响因子：
9.8
通讯作者：
Sadovsky, Y
中科院分区：
文献类型：
--
作者：
Nelson, DM;Johnson, RD;Sadovsky, Y
目的：我们确定了缺氧条件对细胞分化和前列腺素H合酶表达的影响，在培养的人类长期trophoblast.Study设计：从长期胎盘分离的细胞滋养层细胞培养24-72小时，在一个标准（20%的氧气）或缺氧（1%至2%的氧气）的气氛。滋养层细胞的生化分化通过释放人绒毛膜促性腺激素来确定。对细胞表面桥粒和胞浆内核进行双重细胞化学染色后，通过荧光和共聚焦显微镜检查培养物来评估形态分化。前列腺素H合成酶2的表达测定蛋白质印迹分析和相关的酶活性的免疫测定2前列腺素H合成酶2产品，前列腺素E-2和血栓素。结果：人绒毛膜促性腺激素水平在媒体和syncytiotrophoblast形成显着减少在滋养细胞培养在缺氧条件下，与对照培养的滋养细胞相比，而活力是不变的。缺氧上调滋养层前列腺素H合成酶2的表达，但不是前列腺素H合成酶I和前列腺素E-2和血栓素释放增加。结论：缺氧限制分化，提高培养的绒毛滋养层前列腺素H合成酶2的表达。这些反应可以解释胎盘暴露于减弱的氧气输送的细胞滋养层突出特征。
OBJECTIVE: We determined the effect of hypoxic conditions on cellular differentiation and prostaglandin H synthase expression in cultured human term trophoblast.STUDY DESIGN: Cytotrophoblasts isolated from term placentas were cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmosphere. Trophoblast biochemical differentiation was determined by release of human chorionic gonadotropin. Morphologic differentiation was evaluated by epifluorescent and confocal microscopic examination of cultures after dual cytochemical staining for surface membrane desmosomes and intracytoplasmic nuclei. Prostaglandin H synthase 2 expression was determined by Western blot analysis and correlated with enzyme activity by immunoassay of 2 prostaglandin H synthase 2 products, prostaglandin E-2 and thromboxane.RESULTS: Human chorionic gonadotropin levels in media and syncytiotrophoblast formation were markedly diminished in trophoblast cultured in hypoxia, compared with trophoblast in control cultures, whereas viability was unchanged. Hypoxia up-regulated expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H synthase I and increased prostaglandin E-2 and thromboxane release.CONCLUSIONS: Hypoxia limits differentiation and enhances prostaglandin H synthase 2 expression in cultured villous trophoblast. These responses may account for the cytotrophoblast prominence characteristic of placentas exposed to attenuated oxygen delivery.