US EPA

2510780 

Journal Article 

Genetic research and structural dysplasia assessment of anorectal malformations in neonatal male rats induced by di(n-butyl) phthalate 

Liu, ZH; Li, EH; Xu, DL; Sun, WL; Hong, Y; Zhao, W; Xia, SJ; Jiang, JT 

2016 

Yes 

Environmental Toxicology
ISSN: 1520-4081
EISSN: 1522-7278 

Environ Toxicol. 

31 

3 

261-268 

English 

25213187 

10.1002/tox.22040 

WOS:000370130500001 

https://search.proquest.com/docview/1765110061?accountid=171501
Exit
 

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. 

anorectal malformations; di(n-butyl) phthalate; male rats; neonate; terminal rectum