Novel insights from fetal and placental phenotyping in 3 mouse models of Down syndrome.
Novel insights from fetal and placental phenotyping in 3 mouse models of Down syndrome.
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DOI：
10.1016/j.ajog.2021.03.019
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发表时间：
2021-09
影响因子：
9.8
通讯作者：
Bianchi DW
中科院分区：
文献类型：
--
作者：
Adams AD;Hoffmann V;Koehly L;Guedj F;Bianchi DW
在患有唐氏综合征的人类胎儿中，存在胎盘病理结构异常和生长受限。目前还缺乏关于唐氏综合征小鼠模型早期寿命的信息。本研究的目的是检测三种最常见的唐氏综合征小鼠模型（Ts65Dn、Dp（16）1/Yey、Ts1Cje）的胚胎（E18.5）和胎盘基因型。基于三种唐氏综合征小鼠模型的产前和胎盘表型，我们假设其中一种或多种具有与21三体人胎儿相似的表型，这将使其最适合于子宫内治疗研究。将C57BL6J/6雌性与Dp（16）1/Yey和Ts1Cje雄性交配，将Ts65Dn雌性与C57BL/B6Eic3Sn.BLiAF1/J雄性交配。在E18.5，对母鼠实施安乐死。盲法检查胚胎和胎盘的重量和大小。通过聚合酶链反应鉴定胚胎为整倍体或三体，雄性或雌性。检查了一个亚组（34个整倍体，34个三体）的畸形。当比较整倍体和三体胚胎时，Ts65Dn模型显示出胎儿生长、脑发育和胎盘发育的最大差异。对于Dp（16）1/Yey模型，基因型不影响胎儿生长，但在脑和胎盘发育方面存在差异。对于Ts1 Cje模型，未发现基因型与胎儿生长、大脑发育或胎盘发育之间存在显着相关性。整倍体胚胎没有先天性异常，其中一个被淘汰。在6/12（50%）Dp（16）1/Yey和1/12（8%）Ts1Cje胚胎中观察到肝坏死;在3/10（30%）Ts65 Dn胚胎中观察到肝充血/炎症。Dp（16）1/Yey、Ts65Dn和Ts1Cje胚胎肾盂扩张率分别为42%（5/12）、50%（5/10）和25%（3/12）。1个Ts65Dn和1个Dp（16）1/Yey胚胎有主动脉流出异常。两个Ts1Cje胚胎有室间隔缺损。Ts65Dn胎盘具有增加的海绵滋养层坏死。胎儿和胎盘生长显示出不同品系的不同趋势。先天性畸形主要见于三体胚胎。在唐氏综合征的所有三种小鼠模型（10/34）中存在肝脏异常是一个新的发现。肾盂扩张也很常见（13/34）。未来的研究将检查人类尸检材料，以确定这些发现是否与唐氏综合症婴儿有关。胎盘组织学的差异也观察到菌株之间。
In human fetuses with Down syndrome, placental pathology structural anomalies and growth restriction are present. There is currently a significant lack of information regarding the early lifespan in mouse models of Down syndrome. The objective of this study was to examine embryonic (E18.5) and placental genotypes in the three most common mouse models of Down syndrome (Ts65Dn, Dp(16)1/Yey, Ts1Cje). Based on prenatal and placental phenotyping in three mouse models of Down syndrome we hypothesized that one or more of them would have a similar phenotype to human fetuses with trisomy 21, which would make it the most suitable for in utero treatment studies. C57BL6J/6 females were mated to Dp(16)1/Yey and Ts1Cje males and Ts65Dn females to C57BL/B6Eic3Sn.BLiAF1/J males. At E18.5, dams were euthanized. Embryos and placentas were examined blindly for weight and size. Embryos were characterized as euploid or trisomic, male or female by polymerase chain reaction. A subset (34 euploid, 34 trisomic) was examined for malformations. The Ts65Dn model showed the largest difference in fetal growth, brain development and placental development when comparing euploid and trisomic embryos. For the Dp(16)1/Yey model genotype did not impact fetal growth, but there were differences in brain and placental development. For the Ts1Cje model no significant association was found between genotype and fetal growth, brain development or placental development. Euploid embryos had no congenital anomalies; one was demised. Hepatic necrosis was seen in 6/12 (50%) of Dp(16)1/Yey and 1/12 (8%) Ts1Cje embryos; hepatic congestion/inflammation was observed in 3/10 (30%) Ts65Dn embryos. Renal pelvis dilation was seen in 5/12 (42%) Dp(16)1/Yey, 5/10 (50%) Ts65Dn and 3/12 (25%) Ts1Cje embryos. One Ts65Dn and one Dp(16)1/Yey embryo had an aortic outflow abnormality. Two Ts1Cje embryos had ventricular septal defects. Ts65Dn placentas had increased spongiotrophoblast necrosis Fetal and placental growth showed varying trends across strains. Congenital anomalies were primarily seen in trisomic embryos. The presence of liver abnormalities in all three mouse models of Down syndrome (10/34) is a novel finding. Renal pelvis dilation was also common (13/34). Future research will examine human autopsy material to determine if these findings are relevant to infants with Down syndrome. Differences in placental histology were also observed between strains.
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影响因子：
4.6
作者：
Guedj F;Pennings JL;Massingham LJ;Wick HC;Siegel AE;Tantravahi U;Bianchi DW
通讯作者：
Bianchi DW
DOI：
10.1159/000056997
发表时间：
2001-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Akeson, EC;Lambert, JP;Davisson, MT
通讯作者：
Davisson, MT
影响因子：
3.8
作者：
Alkirav, C;Lu, Y;Adamson, SL
通讯作者：
Adamson, SL
影响因子：
3
作者：
Guseh, Stephanie H.;Little, Sarah E.;Wilkins-Haug, Louise E.
通讯作者：
Wilkins-Haug, Louise E.
影响因子：
3.7
作者：
Deodati A;Argemí J;Germani D;Puglianiello A;Alisi A;De Stefanis C;Ferrero R;Nobili V;Aragón T;Cianfarani S
通讯作者：
Cianfarani S