Prenatal exposure to di-n-butyl phthalate induces anorectal malformations in male rat offspring
Prenatal exposure to di-n-butyl phthalate induces anorectal malformations in male rat offspring
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产前接触邻苯二甲酸二正丁酯会导致雄性大鼠后代肛门直肠畸形
DOI：
10.1016/j.tox.2011.10.008
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发表时间：
2011-12-18
期刊：
影响因子：
4.5
通讯作者：
Xia, Shu-Jie
中科院分区：
文献类型：
--
作者：
Jiang, Jun-Tao;Sun, Wen-Lan;Xia, Shu-Jie
本研究的目的是研究母体暴露于邻苯二甲酸二丁酯（DBP）诱导的雄性大鼠发育异常、组织学畸形和遗传异常。在这里，我们报告了新的发现有关的发育异常导致产前暴露于DBP，这导致显着的肛门直肠畸形（ARM）的雄性大鼠后代。雄性子代ARMs发生率为39.5%，所有异常仔鼠均合并继发性巨结肠。常规影像学、组织学及解剖学检查证实畸形。在雄性大鼠的不同发育阶段，ARMs均表现出体重、肛门生殖器距离、体长（去尾）缩短、腹围增大等发育异常。在PND35时，观察了异常雄鼠的实体器官（脑、心、肝、脾、肺和肾）和生殖器官（睾丸和附睾）的发育异常。此外，在PND 1时，ARMs组雄性大鼠血清睾酮（T）水平显著低于对照组，并伴有末端直肠组织雄激素受体（AR）、音刺猬（Shh）和骨形态发生蛋白4（Bmp4）mRNA表达的降低。这些结果首次明确证明，子宫内暴露于DBP导致雄性大鼠后代发生ARM和随后并发巨结肠的可能性增加。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
The objectives of this study were to investigate the dysplasia, histological malformations, and genetic abnormalities in male rats induced by maternal exposure to di-n-butyl phthalate (DBP). Here we report novel findings concerning developmental abnormalities resulting from prenatal exposure to DBP, which leads to significant anorectal malformations (ARMs) in male rat offspring. The incidence of ARMs was 39.5% in male offspring and all abnormal pups were complicated with secondary megacolon. General images, histological analysis and anatomy examination confirmed the malformation. The development abnormalities such as decreased bodyweight (BW) and anogenital distance (AGD), shortened body lengths (with tail removed), as well as increased abdominal circumference were observed at different developmental stages of ARMs in male rat. The developmental abnormalities in both solid organs (brain, heart, liver, spleen, lung and kidney) and reproductive organs (testes and epididymis) of abnormal pubs on PND35 were also investigated. In addition, the serum testosterone (T) level of ARMs in male rats on PND1 was significantly lower than that of controls with accompanying reduced expression of androgen receptor (AR), sonic hedgehog (Shh) and bone morphogenetic protein 4 (Bmp4) mRNA from tissues of the terminal rectum. These results conclusively demonstrate for the first time that in utero exposure to DBP leads to an increased likelihood for the development of ARMs and subsequent complicating megacolon in male rat offspring. (C) 2011 Elsevier Ireland Ltd. All rights reserved.