Zhang Dongmei, Cheng Dong, Liu Tao, Zhang Yachao, Chen Zi-Jiang, Zhang Cong
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
PLoS One. 2015 Dec 30;10(12):e0145968. doi: 10.1371/journal.pone.0145968. eCollection 2015.
Preeclampsia (PE) is a multisystem disorder unique to Homo sapiens that is known to cause maternal and perinatal mortality and morbidity. Between 5-7% of all pregnancies are affected by PE and it is responsible for approximately 50,000 maternal deaths annually. The pathogenesis of PE remains poorly understood. However, the results of this study indicated that insufficient decidualization plays a significant role. NR5A1 and NR5A2 are orphan members of the Ftz-F1 subfamily of nuclear receptors and are involved in mammal follicular development, female reproduction, steroidogenesis, and decidualization. The expression of NR5A1 and NR5A2 in the human decidua and their functions during decidualization were investigated using in vitro cultured cells by real-time PCR, immunohistochemistry, western blotting, and siRNA techniques. The results demonstrated that the levels of NR5A2 mRNA and protein in the decidual tissues of women with PE were lower than those of normal pregnant women. However, the levels of NR5A1 mRNA and protein did not significantly differ between groups. The expression of NR5A2 was upregulated after in vitro decidualization, but the expression of NR5A1 remained low and showed no difference compared with that of the control cells. Knocking down of NR5A2 in human endometrial stromal cells (hESC) resulted in a significant reduction in their expression of decidualization markers (IGFBP1 and PRL) and signaling pathway molecules (WNT4 and BMP2) (P < 0.05). From these data, we concluded that NR5A2 is pivotal for the decidualization of decidual tissues and cultured human endometrial stromal cells. Disorders of the endometrium in decidual tissues may be associated with the abnormal decidualization thought to cause PE.
子痫前期（PE）是人类特有的一种多系统疾病，已知会导致孕产妇和围产期死亡及发病。所有妊娠中有5%-7%受PE影响，每年约有50000例孕产妇死亡与之相关。PE的发病机制仍知之甚少。然而，本研究结果表明蜕膜化不足起了重要作用。NR5A1和NR5A2是核受体Ftz-F1亚家族的孤儿成员，参与哺乳动物卵泡发育、雌性生殖、类固醇生成和蜕膜化过程。利用体外培养细胞，通过实时PCR、免疫组织化学、蛋白质印迹和小干扰RNA技术，研究了NR5A1和NR5A2在人蜕膜中的表达及其在蜕膜化过程中的功能。结果表明，PE患者蜕膜组织中NR5A2 mRNA和蛋白质水平低于正常孕妇。然而，两组间NR5A1 mRNA和蛋白质水平无显著差异。体外蜕膜化后，NR5A2的表达上调，但NR5A1的表达仍较低，与对照细胞相比无差异。在人子宫内膜基质细胞（hESC）中敲低NR5A2会导致蜕膜化标志物（胰岛素样生长因子结合蛋白1和催乳素）和信号通路分子（WNT4和骨形态发生蛋白2）的表达显著降低（P<0.05）。从这些数据中，我们得出结论，NR5A2对蜕膜组织和培养的人子宫内膜基质细胞的蜕膜化至关重要。蜕膜组织中的子宫内膜紊乱可能与被认为导致PE的异常蜕膜化有关。
