Hansen D K, Grafton T F
Department of Health and Human Services, Food and Drug Administration, Jefferson, Arkansas.
Teratog Carcinog Mutagen. 1994;14(6):281-9. doi: 10.1002/tcm.1770140605.
Previous work demonstrated that rat embryos were more susceptible to the growth retardation effect of the synthetic glucocorticoid dexamethasone (DEX) in vivo than were mouse embryos. The purpose of this study was to examine this species difference using an in vitro system. Embryos of CD rats and CD-1 mice were cultured in a whole embryo culture system with concentrations of DEX from 5 to 250 micrograms/ml. Rat embryos were explanted on day 9 of gestation (GD 9: plug day = GD 0), while mouse embryos were removed on GD 8. After 48 h in culture, each viable embryo was evaluated for morphological score, and the number of somite pairs, crown-rump, and head lengths, as well as DNA and protein concentrations were determined. A reduced morphological score was observed for mouse embryos at 5 micrograms DEX/ml, but a significant decrease in this parameter was only observed at DEX concentrations of > or = 100 micrograms/ml in rat embryos. Significant reductions in the number of somite pairs were observed at 25 micrograms/ml for mouse embryos and 100 micrograms/ml for rat embryos. Crown-rump and head lengths as well as DNA and protein concentrations were significantly decreased at 100 micrograms/ml in mouse embryos and 150 micrograms/ml in rat embryos. Therefore, in vitro mouse embryos were adversely affected by lower concentrations of DEX than were rat embryos for each of the six end points examined in this study. This species sensitivity in vitro could be due to inherent genetic differences or to the slightly different developmental stages evaluated using the culture system.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的研究表明,在体内,大鼠胚胎比小鼠胚胎对合成糖皮质激素地塞米松(DEX)的生长迟缓作用更敏感。本研究的目的是使用体外系统来检验这种物种差异。将CD大鼠和CD-1小鼠的胚胎在全胚胎培养系统中培养,DEX浓度为5至250微克/毫升。大鼠胚胎在妊娠第9天(GD 9:交配日=GD 0)取出,而小鼠胚胎在GD 8取出。培养48小时后,评估每个存活胚胎的形态学评分,并测定体节对数、顶臀长、头长以及DNA和蛋白质浓度。在DEX浓度为5微克/毫升时,观察到小鼠胚胎的形态学评分降低,但仅在大鼠胚胎中DEX浓度≥100微克/毫升时,该参数才显著降低。在DEX浓度为25微克/毫升时,观察到小鼠胚胎的体节对数显著减少,在DEX浓度为100微克/毫升时,大鼠胚胎的体节对数显著减少。在DEX浓度为100微克/毫升时,小鼠胚胎的顶臀长和头长以及DNA和蛋白质浓度显著降低,在DEX浓度为150微克/毫升时,大鼠胚胎的上述指标显著降低。因此,对于本研究中检测的六个终点指标中的每一个,体外培养的小鼠胚胎比大鼠胚胎更容易受到较低浓度DEX的不利影响。体外培养时这种物种敏感性差异可能是由于内在的遗传差异,或者是由于使用培养系统评估的发育阶段略有不同。(摘要截断于250字)