Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.
Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate.
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邻苯二甲酸二正丁酯所致新生雄性大鼠肛门直肠畸形的遗传学研究和结构发育不良评估。
DOI：
10.1002/tox.22040
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发表时间：
2016
影响因子：
4.5
通讯作者：
Jiang Jun-Tao
中科院分区：
文献类型：
--
作者：
Liu Zhi-Hong;Li En-Hui;Xu Dong-Liang;Sun Wen-Lan;Hong Yan;Zhao Wei;Xia Shu-Jie;Jiang Jun-Tao
This study was the first to investigate the genetic abnormalities and structural dysplasia of anorectal malformations (ARMs) in male rats induced by di(n‐butyl) phthalate (DBP). DBP was administered to timed‐pregnant rats to establish the ARM rat model. The incidence of ARMs in male offspring was 39.5%. In neonatal period, decreased body weight and anogenital distance were observed. The general image and histological analysis of male offspring confirmed the presence of ARMs. Anatomical examination of the ARM male rats revealed the dysplasia in solid organs (heart‐lung, liver, spleen, and kidney). The decreases of serum testosterone concentration and androgen receptor expression in terminal rectum were indicative of the antiandrogenic effects of DBP. Moreover, significant decreased mRNA expressions of these androgen‐related genes such as sonic hedgehog, Gli2, Gli3, bone morphogenetic protein 4, Wnt5a, Hoxa13, Hoxd13, fibroblast growth factor 10, and fibroblast growth factor receptor 2 were found in terminal rectum of the ARM male pubs. These results demonstrated that development of ARM rats was impaired by maternal exposure to DBP. The antiandrogenic effects of DBP disturbing the androgen‐related signaling networks might play an important role in the occurrence of ARMs. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 261–268, 2016.
