Overexpression of thioredoxin-1 reduces oxidative stress in the placenta of transgenic mice and promotes fetal growth via glucose metabolism.
Overexpression of thioredoxin-1 reduces oxidative stress in the placenta of transgenic mice and promotes fetal growth via glucose metabolism.
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DOI：
10.1210/en.2007-1682
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发表时间：
2008-08
期刊：
影响因子：
4.8
通讯作者：
T. Umekawa;T. Sugiyama;Tomohisa Kihira;N. Murabayashi;Lingyun Zhang;K. Nagao;Yuki Kamimoto;N. Ma;J. Yodoi;N. Sagawa
中科院分区：
文献类型：
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作者：
T. Umekawa;T. Sugiyama;Tomohisa Kihira;N. Murabayashi;Lingyun Zhang;K. Nagao;Yuki Kamimoto;N. Ma;J. Yodoi;N. Sagawa
氧化应激发生在自由基的产生和清除之间不平衡的地方。妊娠本身是一种氧化应激状态，这是由于胎盘线粒体的代谢活性增加和抗氧化系统的清除能力降低。过量产生活性氧可能与胎儿生长受损有关。然而，抗氧化系统对胎儿生长的生理影响还不清楚。在这项研究中，我们评估了抗氧化系统对胎儿生长的影响，使用人硫氧还蛋白（hTRX）-1过表达转基因（Tg）小鼠。将Tg或C57 BL/6 [野生型（WT）]雄性小鼠与WT雌性小鼠交配，并在妊娠第15天处死母鼠以获得胎仔和胎盘。Tg胎仔明显比WT胎仔重，而两组间胎盘重量无显著差异。免疫组化结果显示，hTRX-1定位于Tg小鼠胎盘滋养层细胞核内。此外，与WT小鼠相比，Tg小鼠中反映氧化应激引起的DNA损伤的8-羟基-2 '-脱氧鸟苷的胎盘表达减少。Tg小鼠胎盘葡萄糖转运蛋白-1 mRNA和蛋白表达显著高于WT小鼠，而葡萄糖转运蛋白-3、IGF和IGF结合蛋白mRNA表达无显著差异。这些结果表明，胎盘和/或全身抗氧化系统可以影响胎儿的生长。特别是，增加的hTRX-1活性和由此产生的修改胎盘氧化还原状态可能通过增加葡萄糖的可用性在胎儿生长中发挥重要作用。
Oxidative stress occurs where there is an imbalance between the production and scavenging of free radicals. Pregnancy per se is a state of oxidative stress due to the increased metabolic activity of placental mitochondria and reduced scavenging ability of antioxidant systems. Overproduction of reactive oxygen species may be associated with impaired fetal growth. However, the physiological influence of antioxidant systems on fetal growth is not well understood. In this study we assessed the effects of antioxidant systems on fetal growth using human thioredoxin (hTRX)-1 overexpressing transgenic (Tg) mice. Tg or C57BL/6 [wild-type (WT)] male mice were mated with WT female mice, and dams were killed to obtain the fetuses and placentas on gestational d 15. Tg fetuses were significantly heavier than WT fetuses, whereas placental weight did not differ significantly between the two groups. Immunohistochemically, hTRX-1 was localized to the nuclei of labyrinthine trophoblasts in Tg mice. In addition, placental expression of 8-hydroxy-2'-deoxyguanosine, which reflects DNA damage caused by oxidative stress, was reduced in Tg mice compared with WT mice. Placental expression of glucose transporter-1 mRNA and protein was significantly higher in Tg mice than WT mice, whereas no significant differences were observed for glucose transporter-3, IGF, and IGF-binding protein mRNA expression. These results suggest that placental and/or systemic antioxidant systems can influence fetal growth. In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose.