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BSP-8
(P)
DOWN-REGULATION OF POSTERIOR HOX GENE EXPRESSION IN THE
DEVELOPING CLOACA IS ASSOCIATED WITH THE DEVELOPMENT OF ANORECTAL
AND UROGENITAL MALFORMATIONS
Parkash MANDHAN
Hamad Medical Corporation, Department of Paediatric Surgery, Halilton, NEW ZEALAND
PURPOSE
In vertebrates, the cloaca develops into the urogenital sinus and distal part of the hindgut. Abnormalities of cloacal
development result in a variety of anorectal and urogenital malformations.Hoxgenes have a key role in the organization
of the vertebrate body. This study evaluated the expression of posteriorHoxgenes in the cloaca and its derivatives in
normal and ETU-exposed rat embryos and fetuses.
MATERIAL AND METHODS
Embryos of pregnant SD females administered 1% ETU (125 mg/kg) on the tenth day of gestation (gD10) were
collected from gD14-17 and gD21. Cloacal development was viewed with serial histology followed by qualitative and
quantitative gene expression studies ofShhand targets,Bmp4andHoxgenes to elucidate the expression pattern of these
genes during each time point.
RESULTS
In ETU exposed fetus incomplete separation of the cloaca was observed leading to a variety of hindgut developmental
abnormalities. Cloacal structures in experimental group rats were smaller and maldeveloped. AdequateHoxgenes
expression was observed during development and separation of cloaca in control group rat fetuses. In experimental
group rat fetuses,HoxA13andHoxD13genes were down regulated and relative expression was inadequate during this
developmental process.
CONCLUSIONS
This study demonstrates that vertebrate 5’-locatedHoxAandHoxDgenes are expressed during the process of cloacal
development and partitioning. Down regulation of these genes during cloacal development and occurrence of a variety
of anorectal and urogenital malformations implies that these genes are critical during this stage of development in
vertebrates.