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ToxSci Advance Access originally published online on September 29, 2004
Toxicological Sciences 2004 82(2):458-467; doi:10.1093/toxsci/kfh283
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.

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

J. Ashby and J. Odum1

Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, U.K.

Received July 28, 2004; accepted September 20, 2004

J. C. Gould et al., 1998, Mol. Cell Endocrinol. 142, 203–214, have reported that administration of 5–150 mg/kg/day BPA to immature rats leads to increases in uterine peroxidase activity and progesterone receptor (PR) protein levels in the absence of a 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 2 µg/kg–800 mg/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 4 h and 72 h after the first of three daily po administrations of BPA. Increases in gene expression were observed over the uterotrophic dose range (~200–800 mg/kg BPA). Over the dose range 2 µg/kg–20 mg/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.

Key Words: bisphenol A; uterotrophic; gene expression; progesterone receptor.


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