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首页> 外文期刊>Reproductive toxicology >Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats.
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Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats.

机译：发育中饮食中染料木黄酮暴露对雄性和雌性CD（Sprague-Dawley）大鼠的影响。

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Genistein is a naturally occurring isoflavone that interacts with estrogen receptors and multiple other molecular targets. Human exposure to genistein is predominantly through consumption of soy products, including soy-based infant formula and dietary supplements. A dose range-finding study was conducted as a prelude to a multigeneration bioassay to assess potential toxicities associated with genistein consumption. Genistein was administered in a soy- and alfalfa-free diet at 0, 5, 25, 100, 250, 625, or 1250 ppm to pregnant dams starting on Gestation day 7 and continuing throughout pregnancy. Dietary exposure of the dams continued through lactation, and pups were maintained on the same dosed feed as their mother after weaning until sacrifice at Postnatal day 50. Body weight and feed consumption of the treated dams prior to parturition showed a decreasing trend with a significant reduction at the highest dose. Litter birth weight was depressed in the 1250 ppm dose group, and pups of both sexes in that dose group had significantly decreased body weights relative to controls at the time of sacrifice. The most pronounced organ weight effects in the pups were decreased ventral prostate weight in males at the 1250 ppm dose and a trend toward higher pituitary gland to body weight ratios in both sexes. Histopathologic examination of female pups revealed ductal/alveolar hyperplasia of the mammary glands at 250 to 1250 ppm. Ductal/alveolar hyperplasia and hypertrophy also occurred in males, with significant effects seen at 25 ppm and above. Abnormal cellular maturation in the vagina was observed at 625 and 1250 ppm, and abnormal ovarian antral follicles were observed at 1250 ppm. In males, aberrant or delayed spermatogenesis in the seminiferous tubules relative to controls was observed at 1250 ppm. There was a deficit of sperm in the epididymis at 625 and 1250 ppm relative to controls, although testicular spermatid head counts and epididymal spermatozoa counts did not show significant differences from controls at these doses. Both sexes showed an increase in the incidence and/or severity of renal tubal mineralization at doses of 250 ppm and above. Dietary genistein thus produced effects in multiple estrogen-sensitive tissues in males and females that are generally consistent with its estrogenic activity. These effects occurred within exposure ranges achievable in humans.
机译：金雀异黄素是一种天然存在的异黄酮，可与雌激素受体和多种其他分子靶标相互作用。人类接触染料木黄酮主要是通过食用大豆产品，包括基于大豆的婴儿配方食品和膳食补充剂。进行剂量范围研究是多代生物测定法的序幕，以评估与染料木黄酮消耗有关的潜在毒性。从怀孕第7天开始，在怀孕的母犬中，以无大豆和苜蓿的饮食分别以0、5、25、100、250、625或1250 ppm的剂量施用Genistein。通过哺乳期继续对大坝进行饮食暴露，在断奶后幼崽保持与母亲相同的剂量饲料，直到产后第50天处死。分娩前经处理的大坝的体重和饲料消耗呈下降趋势，且显着降低以最高剂量服用。在1250 ppm剂量组中，产仔体重下降，相对于处死时的对照组，该剂量组中的男女幼犬体重均显着降低。在幼崽中，最显着的器官重量影响是男性在1250 ppm剂量下腹侧前列腺重量减少，以及两性中垂体与体重的比值趋于增加的趋势。雌性幼犬的组织病理学检查显示，乳腺的导管/肺泡增生在250至1250 ppm。男性也发生了导管/肺泡增生和肥大，在25 ppm或更高的浓度下有明显的影响。在625和1250 ppm处观察到阴道细胞成熟异常，在1250 ppm处观察到卵巢窦卵泡异常。在男性中，相对于对照，在生精小管中异常或延迟的精子发生在1250 ppm处观察到。相对于对照组，附睾的精子数量为625和1250 ppm，尽管在这些剂量下睾丸的精子数量和附睾的精子数量与对照组没有显着差异。在250 ppm及以上的剂量下，男女都显示肾小管矿化的发生率和/或严重性增加。因此，膳食染料木黄酮在雄性和雌性的多种雌激素敏感组织中产生作用，通常与其雌激素活性相符。这些影响发生在人类可达到的暴露范围内。

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