Takahashi Y I, Smith J E, Winick M, Goodman D S
J Nutr. 1975 Oct;105(10):1299-310. doi: 10.1093/jn/105.10.1299.
Studies were conducted to examine in detail the effects of vitamin A deficiency on fetal growth and development in the rat. The gradations of deficiency were examined in two studies. The first included total vitamin A depletion followed by retinoic acid supplements, and the second included three different levels of restricted intake of retinyl acetate (42, 16, or 8 mug of retinol equivalents/day/kg of body weight) in vitamin A-depleted rats. In the first study, extensive fetal resorption and death were observed in retinoic acid-fed females after day 14 of gestation. These findings confirmed the morphological studies of Thompson and associates (Proc. Roy. Soc. London, Ser. B 159, 510-535, 1964) who found the earliest Detectable histological lesions to be in the placentas at days 15-16 of pregnancy. Analyses were carried out of the total weight, the DNA, RNA, and protein contents of fetuses and placentas of different gestational ages in retinyl ester-fed and retinoic acid-fed females. Biochemical changes indicative of a reduced rate of cell division were observed in both fetus and placenta by day 14 in the retinoic acid-fed rats. The few live fetuses in this group maintained a growth rate of only 60-70% of that of the fetuses of retinyl ester-fed dams after day 14. By contrast, the growth rate of the placentas (of live fetuses) after day 14 of gestation was not as consistently affected by retinol deficiency. Restriction of retinyl acetate intake (in the second study) significantly reduced both the total litter size and the number of live pups per litter. Most of the females in the retinyl acetate-restricted groups delivered pups that had normal body weight and appeared normal on visual inspection. Significant differences from normal controls were seen only in the neonates from dams given 8 mug of retinol equivalents (per kg of body weight per day), which had smaller livers and kidneys than the control neonates. In contrast, the weights of the brains of the neonates in all three retinyl acetate-restricted groups showed no differences from control values. Vitamin A assays on maternal and neonatal sera and livers indicated that the transport of vitamin A across the placenta was well regulated, and suggested that this transport is maintained with high priority in the presence of maternal deficiency. The effects of vitamin A deficiency on fetal growth and development might reflect primary effects on the placenta, with secondary effects on the fetus, or primary direct effects on the fetus itself. The mechanisms of the observed effects remain to be explained.
开展了多项研究以详细考察维生素A缺乏对大鼠胎儿生长发育的影响。在两项研究中对维生素A缺乏的程度进行了考察。第一项研究包括完全耗尽维生素A后补充视黄酸，第二项研究包括在维生素A缺乏的大鼠中限制摄入三种不同水平的醋酸视黄酯（42、16或8微克视黄醇当量/天/千克体重）。在第一项研究中，妊娠第14天之后，给食视黄酸的雌性大鼠出现了广泛的胎儿吸收和死亡。这些发现证实了汤普森及其同事的形态学研究（《伦敦皇家学会学报》，B辑，第159卷，510 - 535页，1964年），他们发现最早可检测到的组织学损伤出现在妊娠第15 - 16天的胎盘。对给食视黄酯和视黄酸的雌性大鼠不同胎龄的胎儿及胎盘的总重量、DNA、RNA和蛋白质含量进行了分析。到第14天，给食视黄酸的大鼠的胎儿和胎盘均观察到表明细胞分裂速率降低的生化变化。该组中少数存活的胎儿在第14天之后的生长速率仅为给食视黄酯的母鼠所产胎儿生长速率的60 - 70%。相比之下，妊娠第14天之后（存活胎儿的）胎盘生长速率受视黄醇缺乏的影响并不那么一致。（在第二项研究中）限制醋酸视黄酯的摄入量显著降低了每窝的总产仔数和存活幼崽数。醋酸视黄酯限制组中的大多数雌性大鼠产下的幼崽体重正常，外观检查也正常。仅在给予8微克视黄醇当量（每千克体重每天）的母鼠所产的新生幼崽中观察到与正常对照组有显著差异，这些新生幼崽的肝脏和肾脏比对照新生幼崽的小。相比之下，所有三个醋酸视黄酯限制组的新生幼崽的脑重量与对照值无差异。对母体和新生幼崽的血清及肝脏进行的维生素A测定表明，维生素A跨胎盘的转运受到良好调节，这表明在母体缺乏的情况下，这种转运被高度优先维持。维生素A缺乏对胎儿生长发育的影响可能反映了对胎盘的原发性影响以及对胎儿的继发性影响，或者是对胎儿本身的原发性直接影响。所观察到的这些影响的机制仍有待解释。
