Coll Tamara A, Chaufan Gabriela, Pérez-Tito Leticia, Ventureira Martín R, Sobarzo Cristian M A, Ríos de Molina María Del Carmen, Cebral Elisa
Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina.
CONICET-Universidad de Buenos Aires, Instituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE), Ciudad Autonoma de Buenos Aires, Buenos Aires, Argentina.
Mol Reprod Dev. 2017 Oct;84(10):1086-1099. doi: 10.1002/mrd.22865. Epub 2017 Aug 7.
Perigestational alcohol consumption by CF-1 mouse, from before mating up to the period of embryo organogenesis, leads to retarded early embryo development and neural tube defects. Here, we addressed if perigestational alcohol ingestion up to Day 10 of pregnancy induces oxidative stress and changes in macromolecules and organ tissues of early organogenic embryos. Adult CF-1 female mice were administered 10% ethanol in their drinking water for 17 days prior to mating and until Day 10 of gestation, whereas control females were administered ethanol-free water. Our results demonstrated significantly reduced Catalase abundance and activity and increased glutathione content in the embryos of ethanol-treated females. The nitrite level was significantly reduced, but TBARS (thiobarbituric acid reactive substances) content, an index of lipid peroxidation, did not change. Embryos derived from ethanol-treated females also showed higher abundance of 3-nitrotyrosine (3-NT)-containing proteins in all tissues, compared to the control group. Apoptosis was significantly increased in the ectoderm and mesoderm, but not in the heart-although this organ did contain more cleaved Caspase-3-positive cardiomyocytes per area of ventricular myocardium than controls. In sum, moderate perigestational alcohol ingestion up to Day 10 of gestation in mice induces oxidative stress by altering radical nitrogen species and antioxidant enzymatic and non-enzymatic mechanisms in embryos. Further, generalized protein nitration, due to unbalanced nitric oxide levels associated with tissue-specific apoptosis, was detected in embryos, suggesting that oxidative mechanisms may play an important role in the perigestational alcohol-induced malformation of organogenic embryos exposed to ethanol.
CF-1小鼠在围孕期（从交配前到胚胎器官形成期）摄入酒精，会导致早期胚胎发育迟缓以及神经管缺陷。在此，我们研究了妊娠第10天之前的围孕期酒精摄入是否会诱导氧化应激以及早期器官形成胚胎的大分子和器官组织发生变化。成年CF-1雌性小鼠在交配前17天直至妊娠第10天，饮用含10%乙醇的水，而对照雌性小鼠饮用无乙醇的水。我们的结果表明，乙醇处理组雌性小鼠胚胎中的过氧化氢酶丰度和活性显著降低，谷胱甘肽含量增加。亚硝酸盐水平显著降低，但脂质过氧化指标硫代巴比妥酸反应性物质（TBARS）含量没有变化。与对照组相比，乙醇处理组雌性小鼠的胚胎在所有组织中还显示出含3-硝基酪氨酸（3-NT）蛋白质的丰度更高。外胚层和中胚层的细胞凋亡显著增加，但心脏中没有——尽管该器官每单位心室心肌面积中裂解的半胱天冬酶-3阳性心肌细胞确实比对照组多。总之，小鼠在妊娠第10天之前适度的围孕期酒精摄入通过改变胚胎中的活性氮物质以及抗氧化酶和非酶机制诱导氧化应激。此外，在胚胎中检测到由于与组织特异性细胞凋亡相关的一氧化氮水平失衡导致的普遍蛋白质硝化，这表明氧化机制可能在围孕期酒精诱导的暴露于乙醇的器官形成胚胎畸形中起重要作用。
