Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring
Effects of maternal xenoestrogen exposure on development of the reproductive tract and mammary gland in female CD-1 mouse offspring
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DOI：
10.1016/j.reprotox.2004.05.002
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发表时间：
2004-08-01
影响因子：
3.3
通讯作者：
Tsubura, A
中科院分区：
文献类型：
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作者：
Nikaido, Y;Yoshizawa, K;Tsubura, A
本研究的目的是检查母体暴露于相当于或高于人类暴露水平的异种雌激素对雌性CD-1小鼠后代生殖道和乳腺发育的影响。研究了染料木黄酮（GEN）、白藜芦醇（RES）、玉米赤霉烯酮（ZEA）、双酚A（BPA）和己烯雌酚（DES）的作用。从妊娠第15天开始，向妊娠CD-1小鼠皮下注射0.5或10 mg/kg/天GEN、RES、ZEA或BPA，0.5或10 μ g/kg/天溶于二甲基亚砜（DMSO）的DES，或DMSO载体（n = 6），每天4次。监测阴道开口，每组6只动物在4、8、12和16周龄时进行尸检，并监测9至11周龄的发情周期。母体暴露于异种雌激素加速青春期开始（阴道张开）并增加发情周期的长度; GEN、RES、BPA或DES处理的小鼠在动情间期花费更多时间，ZEA处理的小鼠在动情期花费更多时间。高剂量GEN组（33%）和RES组（17%）以及高剂量和低剂量BPA组（分别为33%和50%）和DES组（分别为83%和100%）在4周龄时观察到黄体缺乏和阴道角化。在4、8、12和16周龄时，在高剂量ZEA组中观察到黄体缺乏和阴道角化（分别为83、100、83和33%）。在4周龄时，ZEA和BPA处理的黄体小鼠的乳腺分化加速。无黄体的ZEA处理小鼠在8、12和16周龄时表现出乳腺生长停滞;其乳腺仅由充满分泌液的扩张导管组成。在所有时间点，除ZEA或BPA外，使用外源性雌激素的乳腺生长与对照组相似。高剂量GEN和RES以及高剂量和低剂量BPA和DES对生殖道和乳腺产生短暂影响，而ZEA产生长期影响。(C)2004年爱思唯尔公司All rights reserved.
The objective of this study was to examine the effects of maternal exposure to xenoestrogen, at levels comparable to or greater than human exposure, on development of the reproductive tract and mammary glands in female CD-I mouse offspring. Effects of genistein (GEN), resveratrol (RES), zearalenone (ZEA), bisphenol A (BPA) and diethylstilbestrol (DES) were examined. Beginning on gestational day 15, pregnant CD-1 mice were administered four daily subcutaneous injections with 0.5 or 10 mg/kg/day of GEN, RES, ZEA or BPA, 0.5 or 10 mug/kg/day of DES dissolved in dimethylsulfoxide (DMSO), or DMSO vehicle (n = 6). Vaginal opening was monitored, 6 animals per group were autopsied at 4, 8, 12 and 16 weeks of age and estrous cyclicity was monitored from 9 to I I weeks of age. Maternal exposure to xenoestrogen accelerated puberty onset (vaginal opening) and increased the length of the estrous cycle; mice treated with GEN, RES, BPA or DES spent more time in diestrus, and ZEA-treated mice spent more time in estrus. Lack of corpora lutea and vaginal cornification were observed at 4 weeks of age in the high-dose GEN (33%) and RES (17%) groups, and in the high- and low-dose BPA groups (33 and 50%, respectively) and DES groups (83 and 100%, respectively). Lack of corpora lutea and vaginal cornification was observed in the high-dose ZEA group at 4, 8, 12 and 16 weeks of age (83, 100, 83 and 33%, respectively). Mammary gland differentiation was accelerated in ZEA-and BPA-treated mice with corpora lutea at 4 weeks of age. ZEA-treated mice without corpora lutea showed mammary growth arrest at 8, 12 and 16 weeks of age; their mammary glands consisted only of a dilatated duct filled with secreted fluid. Mammary gland growth was similar with xenoestrogens other than ZEA or BPA to that of the controls at all time points. High-dose GEN and RES and high- and low-dose BPA and DES exerted transient effects on the reproductive tract and mammary glands, whereas ZEA exerted prolonged effects. (C) 2004 Elsevier Inc. All rights reserved.