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ToxSci Advance Access published online on September 29, 2004

Toxicological Sciences, doi:10.1093/toxsci/kfh283
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received July 28, 2004
Accepted September 20, 2004

Endocrine Toxicology

Gene Expression Changes in the Immature Rat Uterus: Effects of Uterotrophic and Sub-Uterotrophic Doses of Bisphenol A

J. Ashby 1 and J. Odum 1*

1 Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, UK

* To whom correspondence should be addressed. E-mail: Jenny.Odum{at}Syngenta.com.


   Abstract

Gould et al. (1998) have reported that administration of 5-150mg/kg/day BPA to immature rats leads to increases in uterine peroxidase activity and progesterone receptor (PR) protein levels in the absence of an uterotrophic response. These observations are of interest given current concerns regarding the adequacy of the uterotrophic assay to act as a sentinel for the estrogenic activity of chemicals in vivo. Therefore, the uterotrophic activity of BPA to the immature rat has been re-evaluated over the dose range 2µg/kg-800mg/kg/day. Expression levels of three estrogen responsive uterine genes were determined using real-time RT-PCR - namely, complement component 3, lipocalin 2 and PR. 18S rRNA and RNA polymerase II large subunit acted as control genes. Observations of gene expression were made 4h and 72h after the first of three daily oral administrations of BPA. Increases in gene expression were observed over the uterotrophic dose range (~200-800mg/kg BPA). Over the dose range 2µg/kg-20mg/kg BPA there was no uterotrophic response and no increase in gene expression. We conclude that BPA does not produce reproducible changes in gene expression in the uterus of immature rats at dose levels that are not also uterotrophic. Therefore, in the present study, the no effect level for uterotrophic activity for BPA coincided with the no transcriptional effect level for uterine genes.

Keywords: Bisphenol A; uterotrophic; gene expression; progesterone receptor.
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