Keiver Kathy, Weinberg Joanne
Food, Nutrition and Health, Faculty of Agricultural Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
Alcohol Clin Exp Res. 2004 Mar;28(3):456-67. doi: 10.1097/01.alc.0000118312.38204.c5.
Prenatal ethanol exposure can retard fetal growth and delay skeletal development. Ethanol also impairs maternal calcium (Ca) homeostasis and this impairment could mediate some of ethanol's effects on the fetal skeleton. Our previous studies suggest that the duration of maternal ethanol consumption may be an important factor for determining the severity of ethanol's effects on Ca homeostasis and fetal skeletal development. The purpose of this study was, therefore, to determine the effect of the duration of maternal ethanol consumption on fetal growth and skeletal development and to investigate the possibility that ethanol's effects may be related to perturbations in fetal/maternal Ca homeostasis.
Rats were fed ethanol (36% ethanol-derived calories) in liquid diets for 3 weeks (days 1-21 of gestation) or 6 weeks (for 3 weeks before and throughout gestation). Fetuses were collected on day 21 of gestation, and body weight and length were measured. Fetuses were stained to determine the degree of skeletal ossification, and fetal blood was analyzed for ethanol, Ca (total and ionic Ca), albumin, parathyroid hormone (PTH), and osteocalcin.
Maternal ethanol consumption decreased fetal growth and delayed fetal skeletal development. Although there was a trend for fetal body length and serum osteocalcin levels to be more severely affected with an increased duration of maternal ethanol consumption, duration had no effect on fetal body weight or skeletal ossification. Fetal Ca homeostasis was also affected by ethanol exposure, with fetal hypocalcemia apparent after 6 weeks of maternal ethanol intake. A significant inverse relationship was found between fetal blood Ca levels and blood alcohol concentration (BAC), suggesting that the severity of the fetal hypocalcemia may have been related to differences in fetal BAC, rather than duration of maternal ethanol intake. Fetal serum PTH levels did not differ significantly among treatment groups indicating that the fetal hypocalcemia was not caused by a decrease in PTH levels.
Prenatal ethanol exposure impaired Ca homeostasis and skeletal development in the fetal rat. The severity of ethanol's effects was only marginally dependent on the duration of maternal ethanol consumption per se and seemed to be more related to the relative exposure of the fetus to ethanol (fetal BAC). The relationship between the ethanol-induced fetal hypocalcemia and skeletal effects remains to be determined.
孕期乙醇暴露会阻碍胎儿生长并延迟骨骼发育。乙醇还会损害母体钙（Ca）稳态，这种损害可能介导了乙醇对胎儿骨骼的部分影响。我们之前的研究表明，母体摄入乙醇的时长可能是决定乙醇对钙稳态及胎儿骨骼发育影响严重程度的一个重要因素。因此，本研究的目的是确定母体摄入乙醇的时长对胎儿生长和骨骼发育的影响，并探究乙醇的影响可能与胎儿/母体钙稳态紊乱有关的可能性。
给大鼠喂食含乙醇（占热量的36%）的液体饲料3周（妊娠第1 - 21天）或6周（妊娠前3周及整个妊娠期）。在妊娠第21天收集胎儿，测量其体重和体长。对胎儿进行染色以确定骨骼钙化程度，并分析胎儿血液中的乙醇、钙（总钙和离子钙）、白蛋白、甲状旁腺激素（PTH）和骨钙素。
母体摄入乙醇会降低胎儿生长速度并延迟胎儿骨骼发育。尽管随着母体摄入乙醇时长增加，胎儿体长和血清骨钙素水平有受更严重影响的趋势，但时长对胎儿体重或骨骼钙化并无影响。乙醇暴露也会影响胎儿钙稳态，母体摄入乙醇6周后胎儿出现低钙血症。胎儿血钙水平与血乙醇浓度（BAC）之间存在显著负相关，表明胎儿低钙血症的严重程度可能与胎儿BAC的差异有关，而非母体摄入乙醇的时长。各治疗组胎儿血清PTH水平无显著差异，表明胎儿低钙血症并非由PTH水平降低所致。
孕期乙醇暴露会损害胎鼠的钙稳态和骨骼发育。乙醇影响的严重程度仅在一定程度上取决于母体摄入乙醇的时长本身，似乎更多地与胎儿对乙醇的相对暴露量（胎儿BAC）有关。乙醇诱导的胎儿低钙血症与骨骼影响之间的关系仍有待确定。
