Strain differences in developmental vulnerability to alcohol exposure via embryo culture in mice.
Strain differences in developmental vulnerability to alcohol exposure via embryo culture in mice.
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DOI：
10.1111/j.1530-0277.2011.01465.x
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发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
Zhou FC
中科院分区：
文献类型：
--
作者：
Chen Y;Ozturk NC;Ni L;Goodlett C;Zhou FC
产前酒精暴露可导致不同程度的神经发育缺陷、生长迟缓和面部畸形。这些不良后果的变化不仅取决于酒精暴露的剂量和模式，而且还取决于环境、遗传和母体因素之间的相互作用。目前的研究验证了胎儿基因型是乙醇致畸的重要决定因素的假设，通过胚胎培养评估乙醇暴露对三种已知在体内产前酒精暴露易损性不同的近交小鼠的影响。对C57BL/6N （B6）、DBA/2 （D2）和129S6/SvEvTac (129S6) 3株小鼠在胚胎日8.25 （E8.25）开始的全胚培养中进行了评估，分别在88mM下给予或不给予酒精6小时，然后在无乙醇培养基中培养42小时。使用Maele-Fabry和Picard评分系统观察大脑、面部和其他器官系统的易感性差异。B6小鼠的前脑、中脑、后脑、心脏、视神经泡、尾神经管和后肢的生长均严重迟缓，而D2小鼠与对照组相比，仅前脑和视神经泡发育迟缓，129S6小鼠未见影响。在脑区、视囊区、脑神经核V、VII、VIII、IX区以及颅面原始区发现大量裂解(c)-caspase3阳性（+）细胞；在B6对照的相应区域只发现少量。相比之下，在D2胚胎和129S6胚胎的酒精处理或对照中，只有少量的c-caspase 3-im细胞被发现。独立凋亡标志物TUNEL和尼罗蓝染色进一步证实了神经管和颅面原基细胞凋亡反应的应变差异。在控制酒精暴露因素和胎儿发育分期、消除母体和宫内因素的胚胎培养条件下，不同品系的生长发育迟缓程度、神经发育畸形的程度和类型存在显著差异。值得注意的是，129S6菌株对酒精诱导的生长缺陷具有显著的抗性，证实了之前的体内研究，D2菌株受酒精诱导的生长缺陷的影响也明显小于B6菌株。这些发现表明胎儿基因型是胎儿酒精谱系障碍变异的重要因素。
Prenatal alcohol exposure can result in varying degrees of neurodevelopmental deficits, growth retardation, and facial dysmorphology. Variation in these adverse outcomes not only depends on the dose and pattern of alcohol exposure but also on less well understood interactions among environmental, genetic, and maternal factors. The current study tested the hypothesis that fetal genotype is an important determinant of ethanol teratogenesis by evaluating effects of ethanol exposure via embryo culture in three inbred strains of mice known to differ in the vulnerability of prenatal alcohol exposure in vivo. Three strains of mice, C57BL/6N (B6), DBA/2 (D2), and 129S6/SvEvTac (129S6) were assessed in a whole embryo culture beginning on embryonic day 8.25 (E8.25), with or without alcohol administration at 88mM for 6 hours followed by 42 hrs culture in ethanol-free media. Contrasting strain differences in susceptibility were observed for the brain, the face, and other organ systems using the Maele-Fabry and Picard scoring system. The forebrain, midbrain, hindbrain, heart, optic vesicle, caudal neural tube, and hindlimbs of the B6 mice were severely delayed in growth, whereas compared to the respective controls, only the forebrain and optic vesicle were delayed in the D2 mice, and no effects were found in the 129S6 mice. A large number of cleaved(c)-caspase3 positive (+) cells were found in regions of the brain, optic vesicles, cranial nerve nuclei V, VII, VIII, and IX as well as the craniofacial primordial; only a few were found in corresponding regions of the B6 controls. In contrast, only a small number of c-caspase 3-im cells were found in either the alcohol-treated or the controls of the D2 embryos and in 129S6 embryos. The independent apoptotic markers TUNEL and Nile blue staining further confirmed the strain differences in apoptotic responses in both the neural tube and craniofacial primordia. Under embryo culture conditions, in which alcohol exposure factors and fetal developmental staging were controlled, and maternal and intrauterine factors were eliminated, the degree of growth retardation and the extent and type of neurodevelopmental teratogenesis varied significantly across strains. Notably, the 129S6 strain was remarkably resistant to alcohol-induced growth deficits, confirming a previous in vivo study, and the D2 strain was also significantly less affected than the B6 strain. These findings demonstrate that fetal genotype is an important factor that can contribute to the variation in fetal alcohol spectrum disorder.
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DOI：
10.1002/tera.1420240108
发表时间：
1981-01-01
期刊：
TERATOLOGY
影响因子：
--
作者：
BROWN, NA;FABRO, S
通讯作者：
FABRO, S
影响因子：
12.4
作者：
Fan, Y.;Bergmann, A.
通讯作者：
Bergmann, A.
影响因子：
2.6
作者：
Downing, C;Gilliam, D
通讯作者：
Gilliam, D
影响因子：
2.9
作者：
ABEL, EL
通讯作者：
ABEL, EL
DOI：
10.1111/j.1530-0277.2009.01069.x
发表时间：
2010-01-01
影响因子：
3.2
作者：
Fish, Eric W.;Riday, Thorfinn T.;Malanga, C. J.
通讯作者：
Malanga, C. J.