Podinić Tina, MacAndrew Andie, Raha Sandeep
Department of Pediatrics and Graduate Program in Medical Sciences, McMaster University, Hamilton, ON, Canada.
Results Probl Cell Differ. 2024;71:101-125. doi: 10.1007/978-3-031-37936-9_6.
During placentation, villous cytotrophoblast (CTB) stem cells proliferate and fuse, giving rise to the multinucleated syncytiotrophoblast (STB), which represents the terminally differentiated villous layer as well as the maternal-fetal interface. The syncytiotrophoblast is at the forefront of nutrient, gas, and waste exchange while also harboring essential endocrine functions to support pregnancy and fetal development. Considering that mitochondrial dynamics and respiration have been implicated in stem cell fate decisions of several cell types and that the placenta is a mitochondria-rich organ, we will highlight the role of mitochondria in facilitating trophoblast differentiation and maintaining trophoblast function. We discuss both the process of syncytialization and the distinct metabolic characteristics associated with CTB and STB sub-lineages prior to and during syncytialization. As mitochondrial respiration is tightly coupled to redox homeostasis, we emphasize the adaptations of mitochondrial respiration to the hypoxic placental environment. Furthermore, we highlight the critical role of mitochondria in conferring the steroidogenic potential of the STB following differentiation. Ultimately, mitochondrial function and morphological changes centrally regulate respiration and influence trophoblast fate decisions through the production of reactive oxygen species (ROS), whose levels modulate the transcriptional activation or suppression of pluripotency or commitment genes.
在胎盘形成过程中，绒毛细胞滋养层（CTB）干细胞增殖并融合，产生多核合体滋养层（STB），后者代表终末分化的绒毛层以及母胎界面。合体滋养层处于营养、气体和废物交换的前沿，同时还具有支持妊娠和胎儿发育的重要内分泌功能。鉴于线粒体动力学和呼吸作用与多种细胞类型的干细胞命运决定有关，且胎盘是一个富含线粒体的器官，我们将着重阐述线粒体在促进滋养层细胞分化和维持滋养层细胞功能方面的作用。我们将讨论合体化过程以及合体化之前和期间与CTB和STB亚谱系相关的独特代谢特征。由于线粒体呼吸与氧化还原稳态紧密相关，我们强调线粒体呼吸对缺氧胎盘环境的适应性。此外，我们突出了线粒体在赋予分化后STB类固醇生成潜能方面的关键作用。最终，线粒体功能和形态变化通过产生活性氧（ROS）来集中调节呼吸作用并影响滋养层细胞的命运决定，ROS的水平可调节多能性或定向分化基因的转录激活或抑制。
