Oral Exposure to Genistin, the Glycosylated Form of Genistein, during Neonatal Life Adversely Affects the Female Reproductive System
Oral Exposure to Genistin, the Glycosylated Form of Genistein, during Neonatal Life Adversely Affects the Female Reproductive System
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DOI：
10.1289/ehp.0900923
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发表时间：
2009-12-01
影响因子：
10.4
通讯作者：
Newbold, Retha
中科院分区：
文献类型：
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作者：
Jefferson, Wendy N.;Doerge, Daniel;Newbold, Retha
背景：发育期暴露于环境雌激素与以后生活中的不良后果有关。暴露于染料木黄酮（GIN），大豆产品中发现的植物雌激素染料木黄酮（GEN）的糖基化形式，是令人担忧的，因为大约20%的美国婴儿喂养大豆配方奶粉。在这些婴儿的血清中已经测量到高循环水平的GEN，表明GIN容易被吸收、水解和循环。结果：我们研究了口服GIN是否对新生小鼠具有雌激素性，以及是否对发育中的雌性生殖道造成不良影响。雌性CD-1小鼠在出生后第1-5天用口服GIN处理5、20或25 mg/kg/天），口服GEN（25、37.5或75 mg/kg/天）或皮下GEN（12.5、20或25 mg/kg/天）。在第5天通过测定子宫湿重增加和雌激素反应基因乳铁蛋白的诱导来测量雌激素活性。阴道开口，动情周期，生育能力，卵巢/生殖道的形态学改变进行了检查。结果：口服GIN引起了雌激素反应，在新生儿子宫，而口服GEN的反应要弱得多。口服GIN改变卵巢分化（即，多卵细胞卵泡），延迟阴道开口，引起异常的发情周期，降低生育能力，并推迟partusions.CONCLUSIONS：我们的研究结果支持的想法，即剂量的生理活性化合物达到目标组织，而不是管理的剂量或途径，是最重要的建模化学品暴露。这对于II期代谢能力相对于成年动物不发达的幼龄动物尤其如此。
BACKGROUND: Developmental exposure to environmental estrogens is associated with adverse consequences later in life. Exposure to genistin (GIN), the glycosylated form of the phytoestrogen genistein (GEN) found in soy products, is of concern because approximately 20% of U.S. infants are fed soy formula. High circulating levels of GEN have been measured in the serum of these infants, indicating that GIN is readily absorbed, hydrolyzed, and circulated.OBJECTIVES: We investigated whether orally administered GIN is estrogenic in neonatal mice and whether it causes adverse effects on the developing female reproductive tract.METHODS: Female CD-I mice were treated on postnatal days 1-5 with oral GIN (6.25, 12.5, 25, or 37.5 mg/kg/day; GEN-equivalent doses), oral GEN (25, 37.5, or 75 mg/kg/day), or subcutaneous GEN (12.5, 20, or 25 mg/kg/day). Estrogenic activity was measured on day 5 by determining uterine wet weight gain and induction of the estrogen-responsive gene lactoferrin. Vaginal opening, estrous cyclicity, fertility, and morphologic alterations in the ovary/reproductive tract were examined.RESULTS: Oral GIN elicited an estrogenic response in the neonatal uterus, whereas the response to oral GEN was much weaker. Oral GIN altered ovarian differentiation (i.e., multioocyte follicles), delayed vaginal opening, caused abnormal estrous cycles, decreased fertility, and delayed parturition.CONCLUSIONS: Our results support the idea that the dose of the physiologically active compound reaching the target tissue, rather than the administered dose or route, is most important in modeling chemical exposures. This is particularly true with young animals in which phase II metabolism capacity is underdeveloped relative to adults.