Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-alpha in vitro.
Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-alpha in vitro.
复制标题
在子宫内暴露于母体糖尿病和在体外暴露于高葡萄糖或肿瘤坏死因子-α 的大鼠囊胚中细胞死亡增加。
作者：
S. Pampfer;I. Vanderheyden;Jane E. McCracken;Jarmila Vesela;R. Hertogh
在胚泡成熟过程中发生的细胞死亡的短暂阶段的形态发生功能尚不清楚，但认为其调节是由子宫环境中存活和致死信号之间的微妙平衡引起的。在本文中，我们表明，从糖尿病大鼠囊胚有一个死亡细胞的发生率高于对照胚胎。分化谱系染色表明，增加核碎裂主要发生在内细胞团。此外，末端转移酶介导的dUTP缺口末端标记（TUNEL）表明，在这些囊胚中的非片段化DNA损伤的细胞核的发生率增加。通过定量逆转录-聚合酶链反应分析与细胞凋亡相关的基因clusterin的表达，发现糖尿病大鼠囊胚中其转录物的稳态水平增加。原位杂交显示，约有一半的细胞鉴定为表达丛生蛋白mRNA表现出核碎裂的迹象。体外实验表明，高D-葡萄糖增加了核碎裂、TUNEL标记和丛生蛋白转录。肿瘤坏死因子-α（TNF-α）是一种细胞因子，其合成在糖尿病子宫中上调，不诱导核碎裂，也不诱导clusterin表达，但增加TUNEL阳性细胞核的发生率。这些数据表明，胚泡中过度的细胞死亡，最可能是由葡萄糖和TNF-α等诱导剂对基础自杀程序的过度刺激引起的，可能是与母体糖尿病相关的早期胚胎病的一个促成因素。
The morphogenetic function of the transient phase of cell death that occurs during blastocyst maturation is not known but it is thought that its regulation results from a delicate balance between survival and lethal signals in the uterine milieu. In this paper, we show that blastocysts from diabetic rats have a higher incidence of dead cells than control embryos. Differential lineage staining indicated that increased nuclear fragmentation occurred mainly in the inner cell mass. In addition, terminal transferase-mediated dUTP nick end labeling (TUNEL) demonstrated an increase in the incidence of non-fragmented DNA-damaged nuclei in these blastocysts. Analysis of the expression of clusterin, a gene associated with apoptosis, by quantitative reverse transcription-polymerase chain reaction detected an increase in the steady-state level of its transcripts in blastocysts from diabetic rats. In situ hybridization revealed that about half the cells identified as expressing clusterin mRNA exhibited signs of nuclear fragmentation. In vitro experiments demonstrated that high D-glucose increased nuclear fragmentation, TUNEL labeling and clusterin transcription. Tumor necrosis factor-alpha (TNF-alpha), a cytokine whose synthesis is up-regulated in the diabetic uterus, did not induce nuclear fragmentation nor clusterin expression but increased the incidence of TUNEL-positive nuclei. The data suggest that excessive cell death in the blastocyst, most probably resulting from the overstimulation of a basal suicidal program by such inducers as glucose and TNF-alpha, may be a contributing factor of the early embryopathy associated with maternal diabetes.
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DOI：
--
发表时间：
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期刊：
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影响因子：
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DOI：
--
发表时间：
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期刊：
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影响因子：
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影响因子：
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作者：
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影响因子：
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作者：
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