Medical Genetics Branch (Prenatal Genomics and Therapy Section), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Medical Genetics Branch (Prenatal Genomics and Therapy Section), National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
Placenta. 2020 Jan 1;89:58-66. doi: 10.1016/j.placenta.2019.10.002. Epub 2019 Oct 5.
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.
唐氏综合征（DS）是导致发育障碍的最常见遗传疾病。与 DS 相关的表型复杂，在受影响的个体之间存在差异。DS 胎盘异常包括影响随后向合体滋养层转化的滋养细胞融合差异、异常氧化应激/抗氧化平衡以及在阿尔茨海默病患者大脑中上调的基因表达增加。DS 胎盘提前衰老，表现出异常的矿化证据。唐氏综合征胎儿特别容易出现不良产科结局，包括宫内死亡、死产和生长受限，所有这些都与胎盘功能有关。因此，胎盘可能为理解 DS 个体中观察到的表型变异性提供关键见解，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，已经生成了许多不同的 DS 小鼠模型，以确定许多器官系统发育变化的机制。然而，关于 DS 现有小鼠模型中的胎盘发育知之甚少。鉴于 DS 临床前小鼠模型中胎盘发育的数据相对较少，我们建议未来对新模型和现有模型的评估应定期包括胎盘的组织学和功能评估。在本文中，我们总结了在 DS 人类和小鼠模型的胎盘中进行的研究，突出了知识空白，并为未来的研究提出了方向。
