Ethanol-induced oxidative stress and mitochondrial dysfunction in rat placenta: relevance to pregnancy loss.
Ethanol-induced oxidative stress and mitochondrial dysfunction in rat placenta: relevance to pregnancy loss.
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DOI：
10.1111/j.1530-0277.2009.01106.x
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发表时间：
2010-03-01
期刊：
影响因子：
--
通讯作者：
de la Monte SM
中科院分区：
文献类型：
--
作者：
Gundogan F;Elwood G;Mark P;Feijoo A;Longato L;Tong M;de la Monte SM
怀孕期间饮酒会增加早孕流产的风险，并导致宫内生长受限。我们以前的研究表明，妊娠期长期暴露于乙醇会损害胎盘形成，这种影响与胰岛素和胰岛素生长因子信号传导的抑制有关。由于乙醇也会导致氧化应激和DNA损伤，我们扩大了我们的调查，以评估这些病理过程中的作用，胎盘和胎盘基因表达。妊娠Long Evans大鼠成对饲喂含0%或24%乙醇（按热量计）的流质饲料。胎盘收获妊娠第16天，用于检查DNA损伤，脂质过氧化，细胞凋亡，线粒体基因/蛋白质和激素基因表达与乙醇暴露。孕激素暴露于乙醇增加胎儿吸收，滋养层细胞凋亡/坏死，氧化应激，DNA损伤和脂质过氧化。乙醇的这些不良作用与促凋亡蛋白（Bax和巴克）表达增加和抗凋亡蛋白Bcl-2水平降低有关。此外，滋养层细胞凋亡倾向增加与p53非依赖性p21激活、线粒体基因和蛋白表达减少以及着床和妊娠相关适应所需的催乳素（PRL）家族激素表达失调有关。妊娠期长期暴露于乙醇会增加胎儿死亡，这是由于存活率和线粒体功能受损、氧化应激增加、DNA损伤和脂质过氧化以及胎盘滋养层中催乳素家族激素表达失调所致。
Ethanol consumption during pregnancy increases the risk of early pregnancy loss and causes intrauterine growth restriction. We previously showed that chronic gestational exposure to ethanol impairs placentation, and that this effect is associated with inhibition of insulin and insulin growth factor signaling. Since ethanol also causes oxidative stress and DNA damage, we extended our investigations to assess the role of these pathological processes on placentation and placental gene expression. Pregnant Long Evans rats were pair-fed liquid diets containing 0% or 24% ethanol by caloric content. Placentas harvested on gestation day 16 were used to examine DNA damage, lipid peroxidation, apoptosis, mitochondrial gene/protein and hormonal gene expression in relation to ethanol exposure. Gestational exposure to ethanol increased fetal resorption, and trophoblast apoptosis/necrosis, oxidative stress, DNA damage, and lipid peroxidation. These adverse effects of ethanol were associated with increased expression of pro-apoptotic (Bax and Bak) and reduced levels of the anti-apoptotic Bcl-2 protein. In addition, increased trophoblast apoptosis proneness was associated with p53-independent activation of p21, reduced mitochondrial gene and protein expression, and dysregulated expression of prolactin (PRL) family hormones that are required for implantation and pregnancy-related adaptations. Chronic gestational exposure to ethanol increases fetal demise due to impaired survival and mitochondrial function, increased oxidative stress, DNA damage and lipid peroxidation, and dysregulated expression of prolactin family hormones in placental trophoblasts.
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