Snyder A K, Jiang F, Singh S P
Medical Research Service, Veterans Affairs Medical Center, Chicago, IL 60064.
Alcohol Clin Exp Res. 1992 Jun;16(3):466-70. doi: 10.1111/j.1530-0277.1992.tb01401.x.
We have previously observed correlations between placental glucose transfer and growth of fetuses of ethanol (EtOH)-fed and control rats. In the present study, whole mammalian embryos were used to define the interaction of glucose supply and the effects of EtOH on growth and differentiation. Rat embryos were cultured in 75% normal rat serum from day 9.5 to day 11.5 of gestation. EtOH produced dose-dependent reductions of embryo protein content (mean +/- SEM = 212 +/- 5, 171 +/- 11, 141 +/- 16, and 113 +/- 9 micrograms/embryo in the presence of 0, 25, 50, and 100 mM EtoH, respectively). Somite number was 25.7 +/- 0.3, 23.4 +/- 0.7, 21.8 +/- 0.7, and 21.1 +/- 0.4 under the same conditions. Exposure to ethanol during the first 24 hr in culture decreased embryo protein content to the same extent as exposure for the entire 48-hr culture period. After 46 hr in culture, control and ethanol-exposed embryos were incubated with 14C-glucose for 2 hr. Ethanol produced dose-dependent reductions of CO2 production, anabolic utilization, lactate release, and total glucose utilization. Glucose supplementation (300 mg/dl) significantly increased embryo protein content and each of these glucose utilization parameters. When glucose utilization was expressed relative to embryo protein content, incorporation of the label into embryonic tissues was significantly reduced by ethanol and increased by glucose supplementation. Embryo protein content correlated closely (r = 0.871, p less than 0.0001) with anabolic glucose utilization. Thus, ethanol directly affects embryo glucose utilization, both as an energy source and as a synthetic substrate, in addition to its effects on placental glucose transfer.
我们之前观察到,给大鼠喂食乙醇(EtOH)组与对照组的胎盘葡萄糖转运和胎儿生长之间存在相关性。在本研究中,使用完整的哺乳动物胚胎来确定葡萄糖供应的相互作用以及乙醇对生长和分化的影响。将大鼠胚胎在妊娠第9.5天至第11.5天期间培养于75%的正常大鼠血清中。乙醇产生剂量依赖性的胚胎蛋白质含量降低(在分别存在0、25、50和100 mM乙醇的情况下,平均±标准误=212±5、171±11、141±16和113±9微克/胚胎)。在相同条件下,体节数分别为25.7±0.3、23.4±0.7、21.8±0.7和21.1±0.4。在培养的最初24小时内暴露于乙醇,胚胎蛋白质含量降低的程度与整个48小时培养期暴露的程度相同。培养46小时后,将对照胚胎和暴露于乙醇的胚胎与14C-葡萄糖一起孵育2小时。乙醇产生剂量依赖性的二氧化碳产生、合成代谢利用、乳酸释放和总葡萄糖利用的降低。补充葡萄糖(300 mg/dl)显著增加了胚胎蛋白质含量以及这些葡萄糖利用参数中的每一项。当葡萄糖利用相对于胚胎蛋白质含量表示时,乙醇显著降低了标记物掺入胚胎组织的量,而补充葡萄糖则增加了该量。胚胎蛋白质含量与合成代谢葡萄糖利用密切相关(r = 0.871,p < 0.0001)。因此,乙醇除了影响胎盘葡萄糖转运外,还直接影响胚胎对葡萄糖的利用,无论是作为能量来源还是作为合成底物。