Analysis of '100 milligram per kilogram per day; genestein' vs 'none' on 'Affymetrix RG_U34A Array'
Star DOWN in '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'
Hao2 UP in '100 milligram per kilogram per day; genestein' vs 'none' on 'Affymetrix RG_U34A Array'
Cpa1 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Analysis of '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'
Cyp11a1 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
(Factor value) COMPOUND/17a-ethynylestradiol 0.000001
S100a9 UP in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Scarb1 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Svs5 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
(Factor value) COMPOUND/bisphenol A 0.02
Creg1 UP in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Cpa1 DOWN in '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 10
Star DOWN in '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
Cyp17a1 DOWN in '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/bisphenol A 0.002
Cpa1 DOWN in '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
Insl3 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Star DOWN in '100 milligram per kilogram per day; genestein' vs 'none' on 'Affymetrix RG_U34A Array'
Cyp17a1 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Analysis of '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Star DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Gsta1 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Cyp17a1 DOWN in '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 0.0001
Svs5 DOWN in '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 0.00001
(Factor value) COMPOUND/17a-ethynylestradiol 1
The purpose of this study was to determine 1) the transcriptional program elicited by exposure to three estrogen receptor (ER) agonists: 17 a-ethynyl estradiol (EE), genistein (Ges) and bisphenol A (BPA) during fetal development of the rat testis and epididymis; and 2) whether very low dosages of estrogens (evaluated over five orders of magnitude of dosage) produce unexpected changes in gene expression (i.e., a non-monotonic dose-response curve). In three independently conducted experiments, Sprague-Dawley rats were dosed (s.c.) with 0.001-10mg EE/kg/day, 0.001-100 mg Ges/kg/day or 0.002-400mg BPA/kg/day. While morphological changes in the developing reproductive system were not observed, the gene expression profile of target tissues were modified in a dose-responsive manner. Independent dose-response analyses of the three studies identified 56 genes that are significantly modified by EE, 28 genes by Ges and 15 genes by BPA (out of 8740). Even more genes were observed to be significantly changed when only the high dose is compared with all lower doses: 141, 46 and 67 genes, respectively. Global analyses aimed at detecting genes consistently modified by all of the chemicals identified 52 genes whose expression changed in the same direction across the three chemicals. The dose-response curve for gene expression changes was monotonic for each chemical, with both the number of genes significantly changed and the magnitude of change, for each gene, decreasing with decreasing dose. Using the available annotation of the gene expression changes induced by ER-agonist, our data suggest that a variety of cellular pathways are affected by estrogen exposure. These results indicate that gene expression data are diagnostic of mode of action and, if they are evaluated in the context of traditional toxicological end-points, can be used to elucidate dose-response characteristics.
Cyp17a1 DOWN in '100 milligram per kilogram per day; genestein' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 0.001
Analysis of '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
Calb2 DOWN in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Cyp11a1 DOWN in '10 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 0.5
Hbe1 UP in '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'
(Factor value) COMPOUND/17a-ethynylestradiol 0.01
Myom2 UP in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Cldn5 UP in '0.01 milligram per kilogram per day; 17a-ethynylestradiol' vs 'none' on Affymetrix RAE230A Array
Svs5 DOWN in '400 milligram per kilogram per day; bisphenol A' vs 'none' on 'Affymetrix RG_U34A Array'