Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Gene expression change induced by bisphenol A in mouse urogenital sinus

ABSTRACT: Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is a well-known, ubiquitous estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we first examined the alterations of in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). Next, to investigate the BPA-specific gene alterations related to increases of the E2 levels and aromatase activity, we performed comprehensive gene expression analysis using Affymetrix GeneChip in the BPA-treated or DES-treated male UGS at embryonic day 17th and postnatal day 1st. Pregnant female C57BL/6 mice were exposed to BPA (20 μg/kg/day) or synthetic estrogen Diethylstilbestrol (DES: 0.2 μg/kg/day), which were dissolved in tocopherol-stripped corn oil, on embryonic day 13 (E13) to E16. Between E17 and postnatal day 1 (P1), all animals were terminated by an overdose of isoflurane followed by cervical dislocation. Fetuses were collected at E17, E18, P0, and P1. The bladder and urethra were removed and dissected to isolate UGS and collected in RNA later. To isolate pure UGS, other tissues such as the bladder, urethra, Wolffian duct (WD), seminal vesicle (SV), and Mullerian duct (MD) were removed from both the male and female urogenital tracts. The histopathology of the mouse UGS was then examined by hematoxylin and eosin staining. Total RNA was extracted using the Qiagen mini RNA Easy kit. Each RNAs were linearly amplified and hybridized to Affymetrix GeneChip.

ORGANISM(S): Mus musculus

SUBMITTER: KATSUHIDE IGARASHI

PROVIDER: E-GEOD-24928 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.

Arase Shigeki S Ishii Kenichiro K Igarashi Katsuhide K Aisaki Kenichi K Yoshio Yuko Y Matsushima Ayami A Shimohigashi Yasuyuki Y Arima Kiminobu K Kanno Jun J Sugimura Yoshiki Y

Biology of reproduction 20101201 4

The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mo ...[more]

PMID: 21123812

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Project description:Studies centered at the intersection of embryogenesis and carcinogenesis have identified striking parallels involving signaling pathways that modulate both developmental and neoplastic processes. In the prostate, reciprocal interactions between epithelium and stroma are known to influence neoplasia and also exert morphogenic effects via the urogenital sinus mesenchyme. In this study, we sought to determine molecular relationships between aspects of normal prostate development and prostate carcinogenesis. We first characterized the gene expression program associated with key points of murine prostate organogenesis spanning the initial in utero induction of prostate budding through maturity. We identified a highly reproducible temporal program of gene expression that partitioned according to the broad developmental stages of prostate induction, branching morphogenesis, and secretory differentiation. Comparisons of gene expression profiles of murine prostate cancers arising in the context of genetically engineered alterations in the Pten tumor suppressor and Myc oncogene identified significant associations between the profile of branching morphogenesis and both cancer models. Further, the expression of genes comprising the branching morphogenesis program, such as PRDX4, SLC43A1, and DNMT3A, was significantly altered in human neoplastic prostate epithelium. These results indicate that components of normal developmental processes are active in prostate neoplasia and provide further rationale for exploiting molecular features of organogenesis to understand cancer phenotypes. Whole male UGS (E14.5, E15.5, E16.5, and E17.5) or separated prostate lobes (P7, P30, and DP90) were dissected from C57BL6/J mice and snap frozen in liquid nitrogen. For each biological replication, we pooled 3 to 10 mice representing one or two litters. RNA from pools of UGS or specific prostate lobes (vp, ap, and dlp) was prepared using the Qiagen RNeasy Mini kit. We included an on-column DNaseI treatment to remove contaminating DNA. Before RNA amplification, we combined equal quantities of RNA from vp, ap, and dlp for the postnatal prostate samples. We amplified 1 ug of total RNA from each sample through one round using the Arcturus RiboAmp kit. For the E14.5 UGS reference sample, a second round of amplification was done to provide enough RNA for all microarrays. Each developmental sample was hybridized against the E14.5 UGS reference sample with a dye swap, for a total of 42 arrays. Warning: the normalized data for this study which was made public on December 1, 2009, was swapped for some samples. All normalized data has now been corrected as of February 25, 2010. Raw data was not affected.

Dataset Information

Gene expression change induced by bisphenol A in mouse urogenital sinus

Publications

Endocrine disrupter bisphenol A increases in situ estrogen production in the mouse urogenital sinus.

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