Mayhew T M
School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.
Placenta. 2014 Apr;35(4):229-40. doi: 10.1016/j.placenta.2014.01.011. Epub 2014 Feb 2.
How the turnover of villous trophoblast is regulated is important for understanding normal and complicated pregnancies. There is considerable accord that syncytiotrophoblast (STB) grows and is refreshed by recruiting post-mitotic cells from the deeper cytotrophoblast (CTB). Nuclei in STB exhibit a spectrum of morphologies and packing densities and, until recently, there seemed to be a consensus that this variation reflected a transition from an early undifferentiated CTB-like phenotype to a long pre-apoptotic and brief apoptotic phase. In these later phases, nuclei are sequestered in clusters (syncytial knots) prior to extrusion as part of normal epithelial turnover. Early in gestation, nuclear clustering and formation of protrusions (syncytial sprouts) also occurs as a preliminary to villous sprouting. Nuclei in these clusters have a CTB-like phenotype and some sprouts may also detach from STB and pass into the uteroplacental circulation. However, this apparent consensus has been challenged and new interpretations of events in the proliferative (CTB), terminal differentiation (STB) and deportation compartments have emerged. Several different types of STB fragment are deported in normal pregnancy: larger multinucleate STB fragments, smaller uninucleate elements with CTB-like morphology, anucleate cytoplasmic fragments, microparticles and nanovesicles. This review identifies points of agreement and disagreement and offers possible avenues of future research. An obvious need is to standardise best practice in several areas including choosing appropriate references for cell cycle phase labelling indices and combining immunolabeling of cell cycle and apoptosis markers (at LM or TEM levels) with design-based stereological estimates of absolute numbers of cells and nuclei in different compartments throughout normal gestation. This would also provide a surer foundation for interpreting results from different research groups and changes in normal and complicated pregnancies.
绒毛滋养层细胞的更新是如何调控的,这对于理解正常和复杂妊娠至关重要。目前人们普遍认为,合体滋养层细胞(STB)通过从更深层的细胞滋养层(CTB)募集有丝分裂后细胞而生长并得到更新。STB中的细胞核呈现出一系列形态和堆积密度,直到最近,似乎有一种共识,即这种变化反映了从早期未分化的CTB样表型到长期的凋亡前期和短暂的凋亡期的转变。在这些后期阶段,细胞核在作为正常上皮更新的一部分被挤出之前会聚集形成簇(合体结节)。在妊娠早期,核聚集和突起(合体芽)的形成也作为绒毛发芽的前奏而发生。这些簇中的细胞核具有CTB样表型,一些芽也可能从STB脱离并进入子宫胎盘循环。然而,这种明显的共识受到了挑战,并且出现了对增殖(CTB)、终末分化(STB)和排出区室中事件的新解释。在正常妊娠中会排出几种不同类型的STB片段:较大的多核STB片段、具有CTB样形态的较小单核成分、无核细胞质片段、微粒和纳米囊泡。本综述确定了一致和不一致的观点,并提供了未来可能的研究途径。一个明显的需求是在几个领域规范最佳实践,包括为细胞周期阶段标记指数选择合适的参考,并将细胞周期和凋亡标记物的免疫标记(在光镜或电镜水平)与基于设计的体视学估计整个正常妊娠不同区室中细胞和细胞核的绝对数量相结合。这也将为解释不同研究小组的结果以及正常和复杂妊娠中的变化提供更可靠的基础。