RGD Reference Report - Maternal exposure to di-n-butyl phthalate (DBP) induces combined anorectal and urogenital malformations in male rat offspring. - Rat Genome Database

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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.
RGD ID: 12743602
Pubmed: PMID:27079746   (View Abstract at PubMed)
DOI: DOI:10.1016/j.reprotox.2016.04.007   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Anorectal Malformations  ISOGli3 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:rectumRGD 
Anorectal Malformations  IEP 12743602; 12743602; 12743602mRNA:decreased expression:rectumRGD 
Anorectal Malformations  ISOHoxa13 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:rectumRGD 
Anorectal Malformations  ISOHoxd13 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:rectumRGD 
hypospadias  ISOGli3 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:male genital tubercle RGD 
hypospadias  IEP 12743602; 12743602; 12743602mRNA:decreased expression:male genital tubercle RGD 
hypospadias  ISOHoxa13 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:male genital tubercle RGD 
hypospadias  ISOHoxd13 (Rattus norvegicus)12743602; 12743602mRNA:decreased expression:male genital tubercle RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gli3  (GLI family zinc finger 3)
Hoxa13  (homeo box A13)
Hoxd13  (homeo box D13)

Genes (Mus musculus)
Gli3  (GLI-Kruppel family member GLI3)
Hoxa13  (homeobox A13)
Hoxd13  (homeobox D13)

Genes (Homo sapiens)
GLI3  (GLI family zinc finger 3)
HOXA13  (homeobox A13)
HOXD13  (homeobox D13)


Additional Information