Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats
Effects of dietary genistein exposure during development on male and female CD (Sprague-Dawley) rats
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DOI：
10.1016/s0890-6238(01)00177-0
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发表时间：
2001-11-01
影响因子：
3.3
通讯作者：
Newbold, RR
中科院分区：
文献类型：
--
作者：
Delclos, KB;Bucci, TJ;Newbold, RR
染料木素是一种天然存在的异黄酮，与雌激素受体和多种其他分子靶点相互作用。人类接触染料木素主要是通过食用豆制品，包括以大豆为基础的婴儿配方奶粉和膳食补充剂。一项剂量范围研究作为多代生物测定的前奏进行，以评估与染料木素摄入相关的潜在毒性。从妊娠第7天开始，在不含大豆和苜蓿的饲粮中分别以0、5、25、100、250、625或t250 ppm的浓度给孕鼠服用染料木素，并持续整个妊娠期。母鼠的饮食暴露持续到哺乳期，幼崽在断奶后保持与母鼠相同的饲料剂量，直到出生后第50天牺牲。产前体重和采食量呈下降趋势，最高剂量显著降低。t250 ppm剂量组的幼崽出生体重下降，并且在牺牲时，该剂量组的雌雄幼崽的体重相对于对照组显着下降。在1250ppm剂量下，幼犬最明显的器官重量影响是雄性前列腺腹侧重量下降，两性垂体与体重之比都有升高的趋势。雌性幼崽的组织病理学检查显示乳腺导管/肺泡增生在250至1250 ppm。导管/肺泡增生和肥大也发生在男性身上，在25ppm及以上的浓度下效果显著。在625和1250 ppm的浓度下观察到阴道内细胞成熟异常，在1250 ppm的浓度下观察到卵巢窦卵泡异常。在雄性中，在ppm浓度为1250时，与对照组相比，精管中精子发生异常或延迟。在ppm浓度为625和1250时，附睾中精子数量不足，尽管在这些剂量下睾丸精细胞头数和附睾精子数量与对照组相比没有显着差异。在剂量为250 ppm及以上时，两性均显示肾管矿化的发生率和/或严重程度增加。因此，膳食染料木素在男性和女性的多种雌激素敏感组织中产生作用，这与它的雌激素活性大致一致。这些影响发生在人类可达到的暴露范围内。(C) 2001爱思唯尔科学公司版权所有。
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 t250 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 t250 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 wag 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. (C) 2001 Elsevier Science Inc. All rights reserved.