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Abstract
The phthalate ester Di(n-butyl) phthalate (DBP)
causes feminization of male rats upon in utero
exposure by repressing expression of genes required for
testicular steroidogenesis. Previous
work in our laboratory has shown that repression of gene
expression and steroidogenesis in the
fetal testis is apparent within a few hours of DBP
exposure. The purpose of this study was to
determine the precise timing of DBP-associated gene
expression changes in the fetal testis using
transcriptional profiling and to determine whether DBP
exerts similar effects on steroidogenesis
in the fetal adrenal. A DBP time course experiment showed
that testicular steroidogenesis was
decreased within one hour of DBP exposure and that this
decrease preceded the repressed
transcription of Star (steroidogenic acute
regulatory protein), Scarb1 (scavenger receptor
class B,
member 1) (also know as Sr-b1), Cyp11a1
(cytochrome P450,
family 11, subfamily a,
polypeptide 1) (also known as P450SCC),
and Cyp17a1
(cytochrome P450 family 17, subfamily a,
polypeptide 1) (also known as Cyp17). Gene expression
profiling demonstrated rapid (within 1
to 3 hours) and transient induction of immediate early
genes in the fetal testis after
administration of DBP to the pregnant dam. There was a
statistically insignificant decrease in
corticosterone production by the fetal adrenal after in
utero exposure to DBP from gd 12 to gd
19. The extent of steroidogenesis diminution was much less
in the adrenal than in the testis
(approximately 45% decrease in the adrenal versus 87%
decrease in the testis) and expression of
genes required for steroidogenesis in the adrenal was
unaffected by DBP. Together these studies
demonstrate that DBP initiates a rapid and dynamic change
in gene expression in the fetal testis
that likely plays a role in the reduction in
steroidogenesis that is unique to the fetal testis relative
to the steroidogenically active fetal adrenal.
Key words:
Male Reproductive Tract •
Testis •
Toxicology •
Adrenal •
Testosterone
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