PS13 DEVELOPMENT OF THE URINARY BLADDER IN ETU‐EXPOSED FETAL RATS IS AFFECTED BY DOWNREGULATION OF SHH AND ITS TARGET GENESCAGES

Abstract

Objective The cloaca develops into the urinary bladder and distal part of the hindgut. Abnormalities of cloacal development result in a variety of anorectal and urogenital malformations. This study evaluated the formation of the urinary bladder in ETU exposed fetal rats in relation to shh and its target genes.Methodology Embryos of pregnant SD females administered 1% ETU (125 mg/kg) on the tenth day of gestation (gD10) were collected from gD12‐16 and gD21. Cloacal development was viewed with serial histology followed by qualitative and quantitative gene expression studies of shh and target genes to elucidate the expression pattern of these genes during each time point.Results ETU exposed fetuses have incomplete separation of the cloaca leading to a variety of anorectal and urinary abnormalities eg rectourethral fistula. Shh and downstream genes are expressed during urinary bladder development in fetal rats. Relative quantification showed that expression of shh, BMP4 and Hox genes are reduced in ETU‐exposed fetal rats during the process of cloacal separation and development of the urinary bladder.Conclusion This study demonstrates that ETU‐exposure in fetal rats produces abnormal cloacal development, including urinary fistulae. Shh cascade is active during the process of cloacal separation and urinary bladder development and down regulation of shh, BMP4 and Hox genes during this process may contribute to the abnormal development of urinary bladder and anorectum.