Department of Pediatrics, Gynecology and Obstetrics, Faculty of Medicine, University of Geneva, 1206, Geneva, Switzerland.
Cell Death Dis. 2019 Sep 9;10(9):651. doi: 10.1038/s41419-019-1905-6.
The syncytiotrophoblast (STB) is a multinuclear layer forming the outer surface of the fetal part of the placenta deriving from villous cytotrophoblastic cell (vCTB) fusion and differentiation. This syncytialization process is characterized by morphological and biochemical alterations of the trophoblast, which probably require removal of pre-existing structures and proteins to maintain cell homeostasis and survival. Interestingly, autophagy, which allows degradation and recycling of cellular components, was shown to be activated in syncytiotrophoblast. Here we examined the involvement of endoplasmic reticulum stress (ERS) response in autophagy activation during vCTB syncytialization. We first demonstrated the activation of ERS response and autophagy during the time course of trophoblastic cell fusion and differentiation. Alteration of autophagy activation in vCTB by chemical treatments or Beclin-1 expression modulation leads to a decrease in trophoblastic syncytialization. Furthermore, ERS response inhibition by chemical treatment or siRNA strategy leads to a default in syncytialization, associated with alteration of autophagy markers and cell survival. From these data, we suggest that ERS response, by fine regulation of autophagy activation, may serve as an adaptive mechanism to promote cell survival during trophoblastic syncytialization.
合体滋养层（STB）是形成胎盘胎儿部分外表面的多核层，源自绒毛滋养层细胞（vCTB）融合和分化。这个合体化过程的特点是滋养层的形态和生化改变，这可能需要去除预先存在的结构和蛋白质，以维持细胞内稳态和存活。有趣的是，自噬允许细胞成分的降解和再循环，已被证明在合体滋养层中被激活。在这里，我们研究了内质网应激（ERS）反应在 vCTB 合体化过程中对自噬激活的参与。我们首先证明了 ERS 反应和自噬在滋养细胞融合和分化的时间过程中被激活。化学处理或 Beclin-1 表达调节改变 vCTB 中的自噬激活会导致滋养细胞合体化减少。此外，化学处理或 siRNA 策略抑制 ERS 反应会导致合体化失败，同时伴随着自噬标志物和细胞存活的改变。从这些数据中，我们认为 ERS 反应通过精细调节自噬激活，可能作为一种适应性机制，促进滋养层合体化过程中的细胞存活。
