Flynn K M, Ferguson S A, Delclos K B, Newbold R R
Division of Neurotoxicology and Division of Biochemical Toxicology, National Center for Toxicological Research, U.S. Food and Drug Administration, Jefferson, Arkansas 72079, USA.
Toxicol Sci. 2000 Jun;55(2):311-9. doi: 10.1093/toxsci/55.2.311.
The phytoestrogen genistein, the principal isoflavone in soybeans, has adverse effects on animal reproduction. As adult physiology and behavior are sensitive to perturbation by developmental estrogens, exposure to genistein during development may produce behavioral alterations as well. Pregnant rats were fed soy-free diets containing 0, 25, 250, or 1250 ppm genistein (approximately 0, 2, 20, or 100 mg/kg/day) beginning on gestational day 7, and offspring continued on these diets through postnatal day (PND) 77. Male and female offspring were assessed for levels of sexually dimorphic behaviors: open field activity, play behavior, running wheel activity, and consumption of saccharin- and sodium chloride-flavored solutions. Consumption of the salt solution was affected by genistein, with animals in the 1250-ppm group drinking significantly more than controls; consumption of plain water was unaffected. Genistein treatment also significantly affected play behavior; although no treated group was significantly different from controls, and the effect was not sexually dimorphic. Running wheel activity and saccharin solution consumption showed significant sex differences, but no effects of genistein treatment. Gestational duration, total and live pups per litter, and total and live litter sex ratios were not significantly affected by genistein. However, average weight per live pup at birth and offspring body weights from PND 42-77 were significantly decreased in the 1250-ppm group. Body weight and food intake for the dams were also significantly decreased in the 1250-ppm group. These results indicate that developmental genistein treatment, at levels that decrease maternal and offspring body weight, causes subtle alterations in some sexually dimorphic behaviors.
植物雌激素染料木黄酮是大豆中的主要异黄酮,对动物繁殖有不良影响。由于成年期的生理和行为对发育过程中雌激素的干扰很敏感,因此在发育过程中接触染料木黄酮也可能导致行为改变。从妊娠第7天开始,给怀孕大鼠喂食含0、25、250或1250 ppm染料木黄酮(约0、2、20或100 mg/kg/天)的无大豆饮食,后代在出生后第77天(PND 77)继续食用这些饮食。对雄性和雌性后代进行性二态性行为水平评估:旷场活动、玩耍行为、转轮活动以及食用糖精和氯化钠调味溶液。染料木黄酮影响了盐溶液的摄入量,1250 ppm组的动物饮水量明显多于对照组;纯水的摄入量未受影响。染料木黄酮处理也显著影响了玩耍行为;尽管没有处理组与对照组有显著差异,且这种影响没有性别差异。转轮活动和糖精溶液摄入量存在显著的性别差异,但染料木黄酮处理没有影响。妊娠期、每窝幼崽总数和存活幼崽数以及幼崽总数和存活幼崽的性别比例均未受到染料木黄酮的显著影响。然而,1250 ppm组出生时每只存活幼崽的平均体重以及出生后第42 - 77天后代的体重显著降低。1250 ppm组母鼠的体重和食物摄入量也显著降低。这些结果表明,发育过程中染料木黄酮处理在降低母体和后代体重的水平上,会导致一些性二态性行为发生细微改变。