Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation
Overexpression of copper zinc superoxide dismutase impairs human trophoblast cell fusion and differentiation
复制标题
DOI：
10.1210/en.142.8.3638
复制
发表时间：
2001-08-01
期刊：
影响因子：
4.8
通讯作者：
Evain-Brion, D
中科院分区：
文献类型：
--
作者：
Frendo, JL;Thérond, P;Evain-Brion, D
合体滋养层是胎盘的主要组成部分，参与母胎交换和分泌妊娠特异性激素。多核合胞体滋养层由单个核细胞滋养层细胞融合而成。在21三体影响的胎盘，我们最近已经表明，有一个缺陷合胞体滋养层形成和减少生产的妊娠特异性激素。由于氧自由基在滋养层细胞分化中的作用，我们研究了21号染色体编码的关键抗氧化酶铜/锌超氧化物歧化酶在体外滋养层细胞分化中的作用。我们首先观察到，超氧化物歧化酶在正常细胞滋养细胞的过度表达损害合体滋养细胞的形成。这与合胞体滋养层的mRNA转录水平和hCG及其他激素标记物的分泌显著降低有关。我们证实了异常细胞融合过表达的绿色荧光蛋白标记的超氧化物歧化酶在细胞滋养层。此外，在超氧化物歧化酶转染的细胞中观察到合胞素转录水平的显着下降。然后，我们研究了超氧化物歧化酶的表达和活性在分离的滋养层细胞从三体21影响的胎盘。超氧化物歧化酶mRNA表达（P
The syncytiotrophoblast is the major component of the human placenta, involved in feto-maternal exchanges and secretion of pregnancy-specific hormones. Multinucleated syncytiotrophoblast arises from fusion of mononuclear cytotrophoblast cells. In trisomy 21-affected placentas, we recently have shown that there is a defect in syncytiotrophoblast formation and a decrease in the production of pregnancy-specific hormones. Due to the role of oxygen free radicals in trophoblast cell differentiation, we investigated the role of the key antioxidant enzyme, copper/zinc superoxide dismutase, encoded by chromosome 21 in in vitro trophoblast differentiation. We first observed that overexpression of superoxide dismutase in normal cytotrophoblasts impaired syncytiotrophoblast formation. This was associated with a significant decrease in mRNA transcript levels and secretion of hCG and other hormonal markers of syncytiotrophoblast. We confirmed abnormal cell fusion by overexpression of green fluorescence protein-tagged superoxide dismutase in cytotrophoblasts. In addition, a significant decrease in syncytin transcript levels was observed in superoxide dismutase-transfected cells. We then examined superoxide dismutase expression and activity in isolated trophoblast cells from trisomy 21-affected placentas. Superoxide dismutase mRNA expression (P