Placental development and function in trisomy 21 and mouse models of Down syndrome: Clues for studying mechanisms underlying atypical development.
Placental development and function in trisomy 21 and mouse models of Down syndrome: Clues for studying mechanisms underlying atypical development.
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DOI：
10.1016/j.placenta.2019.10.002
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发表时间：
2020-01-01
期刊：
影响因子：
3.8
通讯作者：
Bianchi, Diana W.
中科院分区：
文献类型：
--
作者：
Adams, April D.;Guedj, Faycal;Bianchi, Diana W.
唐氏综合症（DS）是导致发育障碍的最常见遗传性疾病。与 DS 相关的表型很复杂，并且在受影响的个体之间存在差异。 DS 中的胎盘异常包括细胞滋养层融合的差异（影响随后向合体滋养层的转化）、非典型氧化应激/抗氧化平衡，以及阿尔茨海默病患者大脑中基因表达的增加。 DS 中的胎盘过早衰老，显示出非典型的矿化证据。患有 DS 的胎儿特别容易出现不良产科结局，包括子宫内早期死亡、死产和生长受限，所有这些都与胎盘功能有关。因此，胎盘可能为了解 DS 个体中观察到的表型变异提供重要见解，并有助于识别可用于实时评估表型严重程度和产前治疗的生物标志物。为了解决这些问题，人们建立了许多不同的 DS 小鼠模型来识别许多器官系统发育变化的机制。然而，对于目前可用的 DS 小鼠模型的胎盘发育知之甚少。基于 DS 临床前小鼠模型胎盘发育数据相对缺乏，我们建议未来对新模型和现有模型的评估通常包括胎盘的组织学和功能评估。在本文中，我们总结了在人类和小鼠 DS 模型胎盘中进行的研究，强调了知识差距并提出了未来研究的方向。
Down syndrome (DS) is the most common genetic disorder leading to developmental disability. The phenotypes associated with DS are complex and vary between affected individuals. Placental abnormalities in DS include differences in cytotrophoblast fusion that affect subsequent conversion to syncytiotrophoblast, atypical oxidative stress/antioxidant balance, and increased expression of genes that are also upregulated in the brains of individuals with Alzheimer’s disease. Placentas in DS are prematurely senescent, showing atypical evidence of mineralization. Fetuses with DS are especially susceptible to adverse obstetric outcomes, including early in utero demise, stillbirth and growth restriction, all of which are related to placental function. The placenta, therefore, may provide key insights towards understanding the phenotypic variability observed in individuals with DS and aid in identifying biomarkers that can be used to evaluate phenotypic severity and prenatal treatments in real time. To address these issues, many different mouse models of DS have been generated to identify the mechanisms underlying developmental changes in many organ systems. Little is known, however, regarding placental development in the currently available mouse models of DS. Based upon the relative paucity of data on placental development in preclinical mouse models of DS, we recommend that future evaluation of new and existing models routinely include histologic and functional assessments of the placenta. In this paper we summarize studies performed in the placentas of both humans and mouse models with DS, highlighting gaps in knowledge and suggesting directions for future research.
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影响因子：
4
作者：
Burton GJ;Jauniaux E
通讯作者：
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