Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor
Apoptosis in human cultured trophoblasts is enhanced by hypoxia and diminished by epidermal growth factor
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DOI：
10.1152/ajpcell.2000.278.5.c982
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发表时间：
2000-05-01
影响因子：
5.5
通讯作者：
Nelson, M
中科院分区：
文献类型：
--
作者：
Levy, R;Smith, SD;Nelson, M
先兆子痫和胎儿生长受限与胎盘灌注不足和绒毛缺氧有关。绒毛对这种环境的反应包括减少滋养层分化和增强细胞凋亡。我们测试的假设，缺氧诱导细胞凋亡在培养的滋养层细胞，表皮生长因子（EGF），滋养层分化的增强剂，减少缺氧诱导的细胞凋亡。从足月无并发症的人妊娠的胎盘分离的滋养层细胞在标准（Po-2 = 120 mmHg）或缺氧（Po-2 < 15 mmHg）条件下培养长达72小时。暴露于缺氧24小时显着增强滋养层细胞凋亡所确定的DNA梯状，internucleosomal原位DNA片段，和组织形态学，以及凋亡过程的可逆性与半胱天冬酶抑制剂。凋亡伴随着p53和Bax表达的增加和Bcl-2表达的减少。添加EGF培养的滋养层细胞或暴露的更分化的滋养层细胞缺氧显着降低细胞凋亡的水平。我们的结论是，缺氧通过一种机制，涉及p53和Bax表达的增加，在培养的滋养层细胞的凋亡增强。EGF和细胞分化的增强对缺氧诱导的细胞凋亡具有保护作用。
Preeclampsia and fetal growth restriction are associated with placental hypoperfusion and villous hypoxia. The villous response to this environment includes diminished trophoblast differentiation and enhanced apoptosis. We tested the hypothesis that hypoxia induces apoptosis in cultured trophoblasts, and that epidermal growth factor (EGF), an enhancer of trophoblast differentiation, diminishes hypoxia-induced apoptosis. Trophoblasts isolated from placentas of term-uncomplicated human pregnancies were cultured up to 72 h in standard (Po-2 = 120 mmHg) or hypoxic (Po-2 < 15 mmHg) conditions. Exposure to hypoxia for 24 h markedly enhanced trophoblast apoptosis as determined by DNA laddering, internucleosomal in situ DNA fragmentation, and histomorphology, as well as by the reversibility of the apoptotic process with a caspase inhibitor. Apoptosis was accompanied by increased expression of p53 and Bax and decreased expression of Bcl-2. Addition of EGF to cultured trophoblasts or exposure of more differentiated trophoblasts to hypoxia significantly lowered the level of apoptosis. We conclude that hypoxia enhances apoptosis in cultured trophoblasts by a mechanism that involves an increase in p53 and Bax expression. EGF and enhancement of cell differentiation protect against hypoxic-induced apoptosis.