Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats.

Exposure to genistein during gestation and lactation demasculinizes the reproductive system in rats.
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DOI:
10.1097/01.ju.0000046780.23389.e0
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发表时间:
2003-04
期刊:
The Journal of urology
影响因子:
--
通讯作者:
A. Wisniewski;S. Klein;Y. Lakshmanan;J. Gearhart
A. Wisniewski;S. Klein;Y. Lakshmanan;J. Gearhart
中科院分区:
其他
文献类型:
--
作者:
A. Wisniewski;S. Klein;Y. Lakshmanan;J. Gearhart

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暴露于植物雌激素染料木黄酮(Indofine Chemical Co.,萨默维尔,新泽西)可以扰乱正常的男性性分化。为了确定围产期(即妊娠期和哺乳期)暴露于人类饮食中常见剂量的染料木黄酮是否会改变雄性化,我们检查了在早期发育过程中暴露于补充染料木黄酮的饮食的雄性大鼠的外生殖器、睾丸、输精管和性行为的发育。材料和方法雌性大鼠在整个妊娠期和哺乳期喂食不含植物雌激素的饲料,饲料中补充无染料木黄酮(游离)、低染料木黄酮剂量(低)或高染料木黄酮剂量(高)。从出生后第2天到第21天,每周测量雄性后代的肛门生殖器距离。在青春期(出生后第40至45天)包皮分离,睾丸的长度和宽度的男性后代进行了测量。在70日龄时,对雄性后代的生殖器官质量、血浆睾酮浓度、精子计数和性行为进行了评估。结果暴露于染料木黄酮导致暂时的,青春期前泌尿生殖系统异常,在出生后第21和40天。暴露于染料木黄酮的男性有较小的肛门生殖器距离和睾丸大小,并延迟包皮分离。围产期暴露于染料木黄酮也引起生殖行为的长期功能障碍,其中暴露于染料木黄酮的成年男性在交配试验中不太可能安装,插入和射精。暴露于染料木黄酮的男性在成年期也有较低的睾酮浓度。结论:围产期染料木素暴露导致生殖系统男性化的短暂和持久改变。这些结果扩展了我们对早期染料木素暴露对男性发育影响的认识,并可能对人类健康产生影响,因为内分泌干扰物和泌尿生殖系统异常之间的潜在关系被认为是男孩和男性发病率增加。
PURPOSE Exposure to the phytoestrogen genistein (Indofine Chemical Co., Somerville, New Jersey) can disrupt normal male sexual differentiation. To determine if perinatal (that is gestation and lactation) genistein exposure at doses common in human diets alters masculinization we examined the development of the external genitalia, testes, wolffian ducts and sexual behavior in male rats exposed to genistein supplemented diets during early development. MATERIALS AND METHODS Female rats were fed a phytoestrogen-free diet supplemented with no genistein (free), a low genistein dose (low) or a high genistein dose (high) throughout gestation and lactation. Anogenital distance of male offspring was measured weekly from postnatal days 2 to 21. At puberty (postnatal day 40 to 45) preputial separation, and testis length and width of male offspring were measured. At age 70 days reproductive organ masses, plasma testosterone concentration, sperm counts and sexual behavior were assessed in male offspring. RESULTS Exposure to genistein resulted in temporary, prepubertal urogenital abnormalities at postnatal days 21 and 40. Males exposed to genistein had smaller anogenital distance and testis size, and delayed preputial separation. Perinatal exposure to genistein also caused long-term dysfunction in reproductive behavior, in which adult males exposed to genistein were less likely to mount, intromit and ejaculate during mating tests. Males exposed to genistein also had lower testosterone concentrations in adulthood. CONCLUSIONS Perinatal genistein exposure results in transient and lasting alterations in masculinization of the reproductive system. These results extend our knowledge of the effects of early genistein exposure on male development and may have implications for human health in terms of potential relationships of endocrine disrupters and urogenital abnormalities thought to be increasing in incidence in boys and men.