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Maternal exposure to di-n-butyl phthalate (DBP) induces combined anorectal and urogenital malformations in male rat offspring.

Authors: Zhu, Yi-Ping  Li, En-Hui  Sun, Wen-Lan  Xu, Dong-Liang  Liu, Zhi-Hong  Zhao, Wei  Wood, Kristofer  Xia, Shu-Jie  Jiang, Jun-Tao 
Citation: Zhu YP, etal., Reprod Toxicol. 2016 Jun;61:169-76. doi: 10.1016/j.reprotox.2016.04.007. Epub 2016 Apr 11.
Pubmed: (View Article at PubMed) PMID:27079746
DOI: Full-text: DOI:10.1016/j.reprotox.2016.04.007

Anorectal malformations in combination with hypospadias (ARMs & hypospadias) are a type of complex congenital malformations. The underlying mechanisms of this deformity are largely unknown. In this study, we comprehensively characterized the dysplasia, histological malformations, and genetic changes of ARMs & hypospadias in male rats after maternal exposure to di-n-butyl phthalate (DBP) by gastric intubation at doses of 850mg/kg bw/day during GD11-15. On postnatal day 1, anatomical and histopathological analysis confirmed combined malformations of the genital tubercle (GT), terminal rectum (TR) and testes. DBP-induced dysplasia was also seen in the kidney, lung, spleen, heart and liver of ARMs & hypospadias male rats. Moreover, decreased levels of serum testosterone, as well as reduced expression of genes related to the androgen signaling pathway (Cyp11a1, Hsd3b, Scarb1, Star, AR, Srd5a2) were found in the testes of ARMs & hypospadias male rats after DBP exposure as compared to untreated controls. Further, decreased mRNA levels of Shh, Fgf10, Gli2, Gli3, Bmp4, Wnt5a, Hoxa13, Hoxd13, Fgfr2 and AR were observed in TR and GT in the ARMs & hypospadias group. These results provide evidence that prenatal exposure to DBP can lead to combined anorectal and urogenital malformations as well as dysplasia of the testes.


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CRRD Object Information
CRRD ID: 12743602
Created: 2017-02-09
Species: All species
Last Modified: 2017-02-09
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.