FOXO1 expression in villous trophoblast of preeclampsia and fetal growth restriction placentas.
FOXO1 expression in villous trophoblast of preeclampsia and fetal growth restriction placentas.
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DOI：
10.14670/hh-30.213
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发表时间：
2015-02
影响因子：
2
通讯作者：
Handwerger S
中科院分区：
文献类型：
--
作者：
Sheridan R;Belludi C;Khoury J;Stanek J;Handwerger S
氧化应激和细胞凋亡增加与许多妊娠疾病的发病机制有关，包括先兆子痫（PE）和胎儿生长受限（FGR）。由于转录因子FOXO1 （forkhead box protein O1）参与了多种细胞过程的调控，包括抗氧化应激、细胞凋亡和胎盘形态发生，我们检测了PE或FGR患者胎盘中FOXO1的表达是否异常。从妊娠晚期早期（31.7±5.0周）轻度PE、重度PE、FGR患者的9个或10个胎盘的中心旁切片和胎龄匹配的对照组（GA对照组）进行FOXO1和E-cadherin的双重免疫染色，后者区分绒毛细胞滋养细胞（CTB）和合胞滋养细胞（STB）。3名对临床结果不知情的观察者在每个胎盘切片的10个20×物镜上检测FOXO1阳性和FOXO1阴性的STB和CTB细胞核数量。结果用广义线性混合模型进行评价。与GA对照组相比，轻度PE中fox01阳性STB细胞核数量显著减少，fox01阴性STB细胞核数量显著增加。然而，与GA对照组相比，foxo1阳性和foxo1阴性的CTB细胞核数量没有显著变化。在严重PE和FGR中，foxo阳性和foxo阴性的STB和CTB数量与GA对照组无统计学差异。由于FOXO1对胎盘细胞形态发生至关重要，FOXO1的异常表达可能在一定程度上导致轻度PE中滋养细胞分化异常。FOXO1在轻度和重度PE中的表达差异与其他研究一致，表明两种PE是不同的疾病过程。
Oxidative stress and increased apoptosis are implicated in the pathogenesis of many disorders of pregnancy, including preeclampsia (PE) and fetal growth restriction (FGR). Since the transcription factor FOXO1 (forkhead box protein O1) is implicated in the regulation of a variety of cellular processes, including resistance to oxidative stress, apoptosis and morphogenesis of the placenta, we examined whether FOXO1 expression is abnormal in placentas from patients with PE or FGR. Paracentral sections from grossly unremarkable areas of 9 or 10 placentas each from early third trimester patients (31.7±5.0 weeks) with mild PE, severe PE, FGR and a gestational age-matched comparison group (GA controls) were double immunostained for FOXO1 and E-cadherin, the latter distinguishing villous cytotrophoblast cells (CTB) from syncytiotrophoblast (STB). The numbers of FOXO1-positive and FOXO1 negative STB and CTB nuclei were determined on ten 20× objective fields of each placenta section by three observers who were blinded to the clinical outcome. The results were evaluated by a generalized linear mixed model. In mild PE, FOXO1-positive STB nuclei were significantly decreased in number and FOXO1-negative STB nuclei were increased as compared to GA controls. However, the number of FOXO1-positive and FOXO1-negative CTB nuclei were not significantly changes as compared to GA controls. In severe PE and FGR, the numbers of FOXO-positive and FOXO1-negative STB and CTB were not statistically different from GA controls. Since FOXO1 is critical for placental cellular morphogenesis, abnormal FOXO1 expression may contribute in part to the abnormal trophoblast differentiation in mild PE. The differences in FOXO1 expression in mild and severe PE are consistent with other studies suggesting that the two forms of PE are different disease processes.