Regulation of Placental Development and Its Impact on Fetal Growth-New Insights From Mouse Models.
Regulation of Placental Development and Its Impact on Fetal Growth-New Insights From Mouse Models.
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DOI：
10.3389/fendo.2018.00570
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发表时间：
2018
影响因子：
5.2
通讯作者：
Hemberger M
中科院分区：
文献类型：
--
作者：
Woods L;Perez-Garcia V;Hemberger M
胎盘是妊娠期发育中胚胎营养供应的主要调节器。因此，足够的胎盘功能有助于整个子宫内发育的发育进展。怀孕期间最常见的并发症之一是胎儿生长不足，这是一个被称为宫内生长受限（IUGR）的问题，最常见的根源是胎盘功能障碍。与传统的基因靶向方法一起，筛选胎盘缺陷小鼠突变体的最新进展，以及通过CRISPR-Cas9技术在体外和体内快速诱导突变的能力，为基因组对正常胎盘发育的贡献提供了新的见解。最重要的是，这些数据表明，正常胎盘形成所需的基因比以前认识到的要多得多。在这里，我们提供了一个总结常见类型的胎盘缺陷在建立小鼠突变，这将有助于我们更好地了解基因影响人类胎盘。基于最近的小鼠突变体筛选，我们提供了如何挖掘这些数据以识别可能对胎盘发育至关重要的新分子枢纽的例子。鉴于胎盘缺陷与心血管和大脑发育异常之间的密切联系，这些功能节点也可能揭示与胎盘畸形同时发生的出生缺陷的病因。总之，最近对小鼠胎盘发育调控的见解为研究开辟了新的途径，这将促进人类妊娠条件的研究，特别是那些基于胎盘缺陷的研究，这些缺陷是最常见的妊娠病理学的基础，如IUGR和先兆子痫。
The placenta is the chief regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental function is instrumental for developmental progression throughout intrauterine development. One of the most common complications during pregnancy is insufficient growth of the fetus, a problem termed intrauterine growth restriction (IUGR) that is most frequently rooted in a malfunctional placenta. Together with conventional gene targeting approaches, recent advances in screening mouse mutants for placental defects, combined with the ability to rapidly induce mutations in vitro and in vivo by CRISPR-Cas9 technology, has provided new insights into the contribution of the genome to normal placental development. Most importantly, these data have demonstrated that far more genes are required for normal placentation than previously appreciated. Here, we provide a summary of common types of placental defects in established mouse mutants, which will help us gain a better understanding of the genes impacting on human placentation. Based on a recent mouse mutant screen, we then provide examples on how these data can be mined to identify novel molecular hubs that may be critical for placental development. Given the close association between placental defects and abnormal cardiovascular and brain development, these functional nodes may also shed light onto the etiology of birth defects that co-occur with placental malformations. Taken together, recent insights into the regulation of mouse placental development have opened up new avenues for research that will promote the study of human pregnancy conditions, notably those based on defects in placentation that underlie the most common pregnancy pathologies such as IUGR and pre-eclampsia.