Developmental cell biology of human villous trophoblast: current research problems

Developmental cell biology of human villous trophoblast: current research problems
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DOI:
10.1387/ijdb.082759ja
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发表时间:
2010-01-01
影响因子:
0.7
通讯作者:
Aplin, John D.
Aplin, John D.
中科院分区:
生物学4区
文献类型:
--
作者:
Aplin, John D.

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常见的妊娠病理是胎盘和发育的起源。然而,关于胎盘形态发生和生长的关键事件仍有许多有待了解。在胎儿和胎盘早期建立的代谢环境决定了它们对后期挑战的反应能力,以及反应的质量。胎盘生长在妊娠早期呈指数级增长,涉及滋养细胞和间充质的协调事件,早期细胞分离事件对生长潜力有很强的影响。其中之一是祖细胞滋养层细胞分化为与合胞体融合的绒毛中间细胞,或者分化为转化母体血管供应的胞外迁移细胞。在后一种情况下,与蜕膜细胞外基质的接触刺激分化,因此这一决定受到胎盘周围接触位点数量的影响,这反过来又是绒毛树分支的功能。绒毛滋养细胞双分子层是母体和胎儿组织之间的主要屏障。面向母体的层是合胞体和有丝分裂后:这限制了病原体向胎儿的运输和由(非增殖的)合胞体元素脱落到母体循环中引起的嵌合。传统的细胞培养模型无法复制这种关键的载体关系。组织外植体可以在一定程度上克服这一问题,并已被用于证明绒毛环境中滋养细胞的周转是由胎儿和母体组织的信号调节的。母体传递的胰岛素样生长因子刺激生长,可能在内源性生长途径不稳定时具有治疗作用。
The common gestational pathologies are placental and developmental in origin. However, much remains to be learned about the key events of morphogenesis and growth in the placenta. Metabolic settings established early in both the fetus and placenta define their capacity to respond to later challenges, as well as the quality of the response. Placental growth is exponential in the first trimester and involves coordinated events in trophoblast and mesenchyme, with early cell segregation events having a strong influence on growth potential. One of these is the differentiation of progenitor cytotrophoblasts into villous intermediate cells programmed to fuse with the syncytium, or, alternatively, into extravillous migratory cells that transform the maternal vascular supply. In the latter case, contact with decidual extracellular matrix stimulates differentiation, and therefore this decision is influenced by the number of contact sites at the placental periphery, which in turn is a function of branching in the villous tree. The villous trophoblast bilayer is the primary barrier between maternal and fetal tissues. The maternal-facing layer is syncytial and post-mitotic: this limits traffic of pathogens to the fetus and chimaerism arising by shedding of (non-proliferative) syncytial elements into maternal circulation. Conventional cell culture models fail to replicate this critical vectorial relationship. Tissue explants can overcome the problem to some extent, and have been used to show that turnover of trophoblast in the villous environment is regulated by signals from both fetal and maternal tissues. Maternally delivered insulin-like growth factors stimulate growth and might be therapeutically useful when endogenous growth pathways falter.