Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of rat efferent ductules treated with the anti-estrogen fulvestrant ICI 182780

ABSTRACT: The aim of this study was to analyze the effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules. Thirty day-old rats were treated once a week for 2 months with vehicle (control group) or ICI 182,780 (AstraZeneca; 10 m g/rat, s.c.). Total RNA of the efferent ductules was extracted using the RNeasy Mini Kit (QIAgen) an further treated with DNAse (QIAgen). Two ug of total RNA were used in the CodeLink Rat Whole Genome Bioarray (GE, Piscataway, NJ), according to the instructions of the manufacturer. The initial analysis was performed with the CodeLink Expression Analysis v4.0 Software (GE). Only genes with at least a 2-fold increase or decrease in expression were selected for further analysis. Statistical analysis was performed with the Significance Analysis of Microarray Program (SAM package).

INSTRUMENT(S): Axon- GenePix4000B

ORGANISM(S): Rattus norvegicus

SUBMITTER: Maria Lazari

PROVIDER: E-MEXP-1497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules.

Yasuhara Fabiana F Gomes Gisele Renata Oliveira GR Siu Erica Rosanna ER Suenaga Cláudia Igushi CI Maróstica Elisabeth E Porto Catarina Segreti CS Lazari Maria Fatima Magalhaes MF

Biology of reproduction 20080521 3

The efferent ductules express the highest amount of estrogen receptors ESR1 (ERalpha) and ESR2 (ERbeta) within the male reproductive tract. Treatment of rats with the antiestrogen fulvestrant (ICI 182,780) causes inhibition of fluid reabsorption in the efferent ductules, leading to seminiferous tubule atrophy and infertility. To provide a more comprehensive knowledge about the molecular targets for estrogen in the rat efferent ductules, we investigated the effects of ICI 182,780 treatment on gen ...[more]

PMID: 18495684

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Project description:Synchrony between embryo competency and uterine receptivity is essential for a successful implantation. Mice with ablation of COUP-TFII in the uterus (PRCre/+;COUP-TFIIflox/flox), exhibit implantation defects and increased ER activity in the luminal epithelium, suggesting the high ER activity may disrupt the window of uterine receptivity. In order to determine if the increased ER activity in PRCre/+;COUP-TFIIflox/flox mutant is the cause of the defective implantation, we inhibited of ER activity in order to rescue the implantation defect in mutant mice. ICI 182,780 (ICI), a pure ER antagonist, was administered to PRCre/+;COUP-TFIIflox/flox mutant and COUP-TFIIflox/flox control mice during receptive period and the number of implantation sites were examined. COUP-TFIIflox/flox control mice treated with oil or ICI showed the normal number of implantation sites. As expected no implantation sites were observed in PRCre/+;COUP-TFIIflox/flox mutant mice treated with oil, consistent with previous observation. However, implantation sites were detected, albeit at a reduced number in comparison to the control in PRCre/+;COUP-TFIIflox/flox mutant mice upon ICI treatment.. ICI treatment was also able to rescue the expression of WNT4 and BMP2, genes important for endometrial decidualization in the PRCre/+;COUP-TFIIflox/flox mutant mice. To ensure the rescue of embryo attachment and decidualization is a consequence of a reduction of estrogen receptor activity with ICI treatment of the mutants, we examined the expression of ER target gene, such as lactoferrin, in PRCre/+;COUP-TFIIflox/flox mutant mice. Having shown that ICI could rescue the implantation and decidualization defects of the PRCre/+;COUP-TFIIflox/flox mutant mice, the ability of ICI treatment to rescue pregnancy in these mice was assayed. While mice were born in COUP-TFIIflox/flox control mice given ICI, no pups were born in the PRCre/+;COUP-TFIIflox/flox mutant mice, with the loss in pregnancy in the PRCre/+;COUP-TFIIflox/flox mutant mice treated with ICI being due to defects in placentation. These results demonstrate that during the peri implantation period, COUP-TFIIâs role in regulating embryo attachment and decidualiton is through the reduction of ER activity. However COUP-TFII expression is still required in the post implantation period to facilitate placentation. Experiment Overall Design: Murine uteri were isolated at 6 hour after oil or ICI 182,780 injection for RNA extraction and hybridization on Affymetrix microarrays. To do this mice were ovariectomized and treated hormones (estrogen and progesterone) to mimic the early pregnant condition.

Project description:The role of estrogen and testosterone in the regulation of gene expression in the proximal reproductive tract is not completely understood. To address this question, mice were treated with testosterone or estradiol and RNA from the efferent ducts and caput epididymis was processed and hybridized to Affymetrix MOE 430 2.0 microarrays. Analysis of array output identified probe sets in each tissue with altered levels in hormone treated versus control animals. Hormone treatment efficacy was confirmed by determination of serum hormone levels pre- and post-treatment and observed changes in transcript levels of previously reported hormone-responsive genes. Tissue-specific hormone sensitivity was observed with 2867 and 3197 probe sets changing significantly in the efferent ducts after estrogen and testosterone treatment, respectively. In the caput epididymis, 117 and 268 probe sets changed after estrogen and testosterone treatment, respectively, demonstrating a greater response to hormone in the efferent ducts than the caput epididymis. Transcripts sharing similar profiles in the intact and hormone-treated animals compared with castrated controls were also identified. Ontological analysis of probe sets revealed a significant number of hormone-regulated transcripts encode proteins associated with lipid metabolism, transcription and steroid metabolism in both tissues. Real-time RT-PCR was employed to confirm array data and investigate other potential hormone-responsive regulators of proximal reproductive tract function. The results of this work reveal previously unknown responses to estrogen in the caput epididymis and to testosterone in the efferent ducts as well as tissue specific hormone sensitivity in the proximal reproductive tract. Adult animals were castrated or sham-castrated, allowed to recover for 14 days, and then treated with 0.015 mg estradiol (castrated), 0.015 mg testosterone propionate (castrated), or vehicle (castrated and sham-castrated as biological controls) in duplicate. Efferent duct and caput epididymis was collected from each sample and analyzed. Duplicates are included in the provided data and numbered 1 or 2 for each treatment regimen.

Dataset Information

Transcription profiling of rat efferent ductules treated with the anti-estrogen fulvestrant ICI 182780

Publications

Effects of the antiestrogen fulvestrant (ICI 182,780) on gene expression of the rat efferent ductules.

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