BACKGROUND Villous cytotrophoblast (vCTB) is a precursor cell population that supports the development of syncytiotrophoblast (vSTB), the high surface area barrier epithelium of the placental villus, and the primary interface between maternal and fetal tissue. In light of increasing evidence that the placenta can adapt to changing maternal environments or, under stress, can trigger maternal disease, we consider what properties of these cells empower them to exert a controlling influence on pregnancy progression and outcome. OBJECTIVE AND RATIONALE How are cytotrophoblast proliferation and differentiation regulated in the human placental villus to allow for the increasing demands of the fetal and environmental challenges and stresses that may arise during pregnancy? SEARCH METHODS PubMed was interrogated using relevant keywords and word roots combining trophoblast, villus/villous, syncytio/syncytium, placenta, stem, transcription factor (and the individual genes), signalling, apoptosis, autophagy (and the respective genes) from 1960 to the present. Since removal of trophoblast from its tissue environment is known to fundamentally change cell growth and differentiation kinetics, research that relied exclusively on cell culture has not been the main focus of this review, though it is mentioned where appropriate. Work on non-human placenta is not systematically covered, though mention is made where relevant hypotheses have emerged. OUTCOMES The synthesis of data from the literature has led to a new hypothesis for vCTB dynamics. We propose that a reversible transition can occur from a reserve population in G0 to a mitotically active state. Cells from the in-cycle population can then differentiate irreversibly to intermediate cells that leave the cycle and turn on genes that confer the capacity to fuse with the overlying vSTB as well as other functions associated with syncytial barrier and transport function. We speculate that alterations in the rate of entry to the cell cycle, or return of cells in the mitotic fraction to G0, can occur in response to environmental challenge. We also review evidence on the life cycle of trophoblast from the time that fusion occurs, and point to gaps in knowledge of how large quantities of fetal DNA arrive in maternal circulation. We critique historical methodology and make a case for research to re-address questions about trophoblast lifecycle and dynamics in normal pregnancy and the common diseases of pre-eclampsia and fetal growth restriction, where altered trophoblast kinetics have long been postulated. WIDER IMPLICATIONS The hypothesis requires experimental testing, moving research away from currently accepted methodology towards a new standard that includes representative cell and tissue sampling, assessment of cell cycle and differentiation parameters, and robust classification of cell subpopulations in villous trophoblast, with due attention to gestational age, maternal and fetal phenotype, disease and outcome.

中文翻译：

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人绒毛滋养层的细胞动力学

背景绒毛细胞滋养层(vCTB)是支持合体滋养层(vSTB)、胎盘绒毛的高表面积屏障上皮以及母体和胎儿组织之间的主要界面发育的前体细胞群。鉴于越来越多的证据表明胎盘可以适应不断变化的母体环境，或者在压力下可以引发母体疾病，我们考虑这些细胞的哪些特性使它们能够对妊娠进展和结果施加控制影响。目标和基本原理 如何调节人胎盘绒毛中的细胞滋养层增殖和分化，以应对胎儿日益增长的需求以及怀孕期间可能出现的环境挑战和压力？搜索方法 PubMed 使用相关的关键词和词根进行查询，包括 1960 年到展示。由于已知从其组织环境中去除滋养层会从根本上改变细胞生长和分化动力学，因此完全依赖细胞培养的研究并不是本次审查的主要焦点，尽管在适当的情况下会提及。非人类胎盘的工作没有系统地涵盖，尽管在出现相关假设的地方提到了。结果 文献数据的综合导致了 vCTB 动力学的新假设。我们建议从 G0 中的保留种群到有丝分裂活跃状态的可逆转变可以发生。然后，来自循环内群体的细胞可以不可逆地分化为中间细胞，这些细胞离开循环并打开赋予与上覆 vSTB 融合能力的基因以及与合胞体屏障和转运功能相关的其他功能。我们推测进入细胞周期的速率的改变，或有丝分裂部分的细胞返回到 G0，可以响应环境挑战而发生。我们还回顾了融合发生时滋养层生命周期的证据，并指出在大量胎儿 DNA 如何进入母体循环方面的知识空白。我们批判了历史方法，并为研究重新解决有关正常妊娠中滋养层生命周期和动力学以及先兆子痫和胎儿生长受限等常见疾病的研究提供了案例，长期以来一直假设这些疾病的滋养层动力学发生了改变。更广泛的影响 该假设需要实验测试，将研究从目前公认的方法转向新标准，包括代表性细胞和组织取样、细胞周期和分化参数的评估，以及绒毛滋养层细胞亚群的稳健分类，并适当注意妊娠期。年龄、母体和胎儿表型、疾病和结果。我们批判了历史方法，并为研究重新解决有关正常妊娠中滋养层生命周期和动力学以及先兆子痫和胎儿生长受限等常见疾病的研究提供了案例，长期以来一直假设这些疾病的滋养层动力学发生了改变。更广泛的影响 该假设需要实验测试，将研究从目前公认的方法转向新标准，包括代表性细胞和组织取样、细胞周期和分化参数的评估，以及绒毛滋养层细胞亚群的稳健分类，并适当注意妊娠期。年龄、母体和胎儿表型、疾病和结果。我们批判了历史方法，并为研究重新解决有关正常妊娠中滋养层生命周期和动力学以及先兆子痫和胎儿生长受限等常见疾病的研究提供了案例，长期以来一直假设这些疾病的滋养层动力学发生了改变。更广泛的影响 该假设需要实验测试，将研究从目前公认的方法转向新标准，包括代表性细胞和组织取样、细胞周期和分化参数的评估，以及绒毛滋养层细胞亚群的稳健分类，并适当注意妊娠期。年龄、母体和胎儿表型、疾病和结果。