Wu Jing, He Zhiming, Gao Yu, Zhang Guanglan, Huang Xuan, Fang Qun
a Department of Obstetrics and Gynecology, Fetal Medicine Center , The First Affiliated Hospital of Sun Yat-sen University , Yuexiu District , Guangzhou City , Guangdong Province , China.
b Department of Obstetrics and Gynecology , The Sixth Affiliated Hospital of Sun Yat-sen University , Guangzhou , Guangdong , China.
Free Radic Res. 2017 Apr;51(4):351-359. doi: 10.1080/10715762.2017.1315113. Epub 2017 Apr 25.
Nuclear factor, erythroid 2 like 2 (NFE2L2) is an important transcription factor that protects cells from oxidative stress (OS). NFE2L2 deficiency in placentas is associated with pregnancy complications. We have demonstrated that elevated OS existed in placental shares of the smaller fetus in selective intrauterine growth restriction (sIUGR); however, the role of NFE2L2 in the development of sIUGR remains unknown. In this study, we examined the levels of NFE2L2 and heme oxygenase 1 (HMOX1), a major antioxidant regulated by NFE2L2, in sIUGR placentas. We also investigated the relationship between hypoxia and NFE2L2 activation, which may be involved in the pathogenesis of sIUGR.
Real-time PCR, Western blot, and immunohistochemistry were used to detect the levels of NFE2L2 and HMOX1 in placentas from 30 monochorionic diamniotic (MCDA) twin pregnancies. The trophoblast cell line HTR-8/SVneo was cultured under severe (3%) or mild (10%) hypoxia.
NFE2L2 and HMOX1 were both up-regulated in placental shares of the smaller fetus in the sIUGR group. No significant inter-twin differences in NFE2L2 and HMOX1 were detected in the normal group. In vitro, NFE2L2 was suppressed under severe hypoxia (3% O) but was clearly up-regulated under mild hypoxia (10% O).
Compared with the suppression of NFE2L2 in placentas of fetal growth restriction (FGR) in singleton pregnancies, NFE2L2 was up-regulated in placental shares of the smaller fetus in sIUGR pregnancies. The asymmetrical activation of NFE2L2 in placental shares of sIUGR twins may be a compensation for hypoxia that protects the smaller fetus from OS damage.
核因子红细胞2样2（NFE2L2）是一种重要的转录因子，可保护细胞免受氧化应激（OS）的影响。胎盘NFE2L2缺乏与妊娠并发症有关。我们已经证明，在选择性宫内生长受限（sIUGR）中，较小胎儿的胎盘部分存在氧化应激升高；然而，NFE2L2在sIUGR发生发展中的作用尚不清楚。在本研究中，我们检测了sIUGR胎盘组织中NFE2L2和血红素加氧酶1（HMOX1，一种由NFE2L2调节的主要抗氧化剂）的水平。我们还研究了缺氧与NFE2L2激活之间的关系，这可能与sIUGR的发病机制有关。
采用实时荧光定量PCR、蛋白质免疫印迹法和免疫组织化学法检测30例单绒毛膜双羊膜囊（MCDA）双胎妊娠胎盘组织中NFE2L2和HMOX1的水平。将滋养层细胞系HTR-8/SVneo在严重（3%）或轻度（10%）缺氧条件下培养。
sIUGR组中较小胎儿的胎盘部分NFE2L2和HMOX1均上调。正常组双胎之间NFE2L2和HMOX1未检测到显著差异。在体外，NFE2L2在严重缺氧（3% O₂）条件下受到抑制，但在轻度缺氧（10% O₂）条件下明显上调。
与单胎妊娠胎儿生长受限（FGR）胎盘组织中NFE2L2受到抑制相比，sIUGR妊娠中较小胎儿的胎盘部分NFE2L2上调。sIUGR双胎胎盘部分NFE2L2的不对称激活可能是对缺氧的一种补偿，可保护较小胎儿免受氧化应激损伤。
