Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.
Fetal growth retardation and lack of hypotaurine in ezrin knockout mice.
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DOI：
10.1371/journal.pone.0105423
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Nakashima E
中科院分区：
文献类型：
--
作者：
Nishimura T;Higuchi K;Sai Y;Sugita Y;Yoshida Y;Tomi M;Wada M;Wakayama T;Tamura A;Tsukita S;Soga T;Nakashima E
Ezrin是一种膜相关的细胞质蛋白，用于连接细胞膜蛋白和基于肌动蛋白的细胞骨架，并对一些跨膜蛋白的功能活性起调节作用。它在胎盘滋养细胞中表达。我们假设胎盘ezrin参与了从母亲到胎儿的营养供应，从而影响胎儿的生长。本研究的目的首先是阐明ezrin对胎儿生长的影响，其次是确定ezrin基因敲除是否与血清和胎盘营养物质浓度降低有关。Ezrin基因敲除小鼠（Ez−/−）被证实表现出胎儿生长迟缓。利用毛细管电泳-飞行时间质谱分析ezrin基因敲除小鼠的胎儿血清和胎盘提取物的代谢组学分析显示，牛磺酸的前体-次牛磺酸的浓度显著降低。然而，胎盘的半胱氨酸和半胱氨酸亚磺酸（次牛磺酸的前体）和牛磺酸水平没有受到影响。用液相色谱-串联质谱法证实Ez - / -小鼠缺乏次牛磺酸。在异质胎坝中给予次牛磺酸显著降低了野生型胎儿的胎盘-母体血浆中次牛磺酸的比例，而在ezrin基因敲除的胎儿中只略微降低了这一比例，这表明从母体到胎盘的次牛磺酸摄取是饱和的，ezrin的破坏损害了胎盘滋养细胞对次牛磺酸的摄取。这些结果表明，ezrin是胎盘滋养细胞从母体血清中摄取次牛磺酸所必需的，并在胎儿生长中起重要作用。
Ezrin is a membrane-associated cytoplasmic protein that serves to link cell-membrane proteins with the actin-based cytoskeleton, and also plays a role in regulation of the functional activities of some transmembrane proteins. It is expressed in placental trophoblasts. We hypothesized that placental ezrin is involved in the supply of nutrients from mother to fetus, thereby influencing fetal growth. The aim of this study was firstly to clarify the effect of ezrin on fetal growth and secondly to determine whether knockout of ezrin is associated with decreased concentrations of serum and placental nutrients. Ezrin knockout mice (Ez−/−) were confirmed to exhibit fetal growth retardation. Metabolome analysis of fetal serum and placental extract of ezrin knockout mice by means of capillary electrophoresis–time-of-flight mass spectrometry revealed a markedly decreased concentration of hypotaurine, a precursor of taurine. However, placental levels of cysteine and cysteine sulfinic acid (precursors of hypotaurine) and taurine were not affected. Lack of hypotaurine in Ez−/− mice was confirmed by liquid chromatography with tandem mass spectrometry. Administration of hypotaurine to heterogenous dams significantly decreased the placenta-to-maternal plasma ratio of hypotaurine in wild-type fetuses but only slightly decreased it in ezrin knockout fetuses, indicating that the uptake of hypotaurine from mother to placenta is saturable and that disruption of ezrin impairs the uptake of hypotaurine by placental trophoblasts. These results indicate that ezrin is required for uptake of hypotaurine from maternal serum by placental trophoblasts, and plays an important role in fetal growth.
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影响因子：
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