Uterine Gene Profile of Estriol, a Weak Estrogen
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ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: NIEHS Microarray Core
PROVIDER: E-GEOD-23241 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:WT and Ex3aERKO females were ovariectomized and injected with saline or estradiol. Uterine tissue was collected after 2 or 24 hours. RNA was analyzed by microarray to determine if the Ex3aERKO mice would lack the residual transcritpional resposnes seen in the previous aERKO model. 3 uteri per group were analyzed individually on one-color Agilent arrays. Comparisons were made within ERa genotype (WT saline to WT E treated; Ex3aERKO saline to Ex3aERKO E treated)
2010-07-22 | E-GEOD-23072 | biostudies-arrayexpress
Project description:Females were ovariectomized and injected with sesame oil, estradiol in sesame oil, BPA in sesame oil or HPTE in sesame oil. Uterine tissue was collected after 2 or 24 hours. RNA was analyzed by microarray compare ealry and late responses to a potent and a weak estrogen agaonist. 3 uteri per group were analyzed individually on one-color Agilent arrays (note: estradiol treatment at 24 hr only has 2 replicates).
2010-10-06 | E-GEOD-24525 | biostudies-arrayexpress
Project description:The growth and development of the uterus in response to 17β-estradiol (E2) is genetically controlled, with marked variation observed depending on the mouse strain studied. Previous work from our laboratory using inbred mice that are high (C57BL6/J; B6) or low (C3H/HeJ; C3H) responders to E2 has led to the identification of quantitative trait loci (QTL) associated with phenotypic variation in uterine growth and eosinophil infiltration. The mechanisms underlying differential responsiveness to E2, and the genes involved, are unknown. Therefore, we used a microarray approach to show association of distinct E2-regulated transcriptional signatures with genetically controlled high and low responses to E2. Among the 6,664 E2-responsive uterine transcripts, several reside within our previously identified QTL, including the ERα-tethering factor Runx1, demonstrated to enhance E2-mediated transcript regulation. The level of RUNX1 in uterine epithelial cells was shown to be 3.5-fold greater in B6 compared to C3H. Analysis of cellular functions in sets of strain-dependent E2-responsive transcripts indicated C3H-selective enrichment of apoptosis, consistent with a 7-fold increase in the apoptosis indicator CASP3, and a 2.4-fold decrease in the apoptosis inhibitor Naip1 in C3H vs. B6 following treatment with E2. Our novel insights into the mechanisms underlying the genetic control of tissue sensitivity to estrogen have great potential to advance understanding of individualized effects in physiological and disease states. Eight-week-old female B6, C3H, and (B6 × C3H)F1 (B6C3) hybrid mice were purchased from The Jackson Laboratory (Bar Harbor, ME). Animals were ovariectomized at NIEHS, rested for 1 to 2 wk, and then subjected to treatment with either E2 (40.0 μg/kg BW injected i.p.) in 0.1 ml saline containing 0.25% ethanol, or ethanol/saline vehicle. Animals were euthanized and tissue collected at 2 or 24 h after injection. Uterine tissue from 3 animals per treatment group was collected, and snap-frozen in liquid nitrogen for subsequent RNA isolation. Frozen uterine tissue from three animals per treatment group was pulverized, then homogenized in Trizol (Invitrogen, Carlsbad, CA), and RNA was prepared according to the manufacturer's protocol. Isolated RNA was then further purified using the QIAGEN (Valencia, CA) RNeasy mini prep kit clean-up protocol. Gene expression analysis was conducted using Agilent Whole Mouse Genome 4x44 Multiplex format oligo arrays (014868; Agilent Technologies, Santa Clara, CA) following the Agilent 1-color microarray-based gene expression analysis protocol. Starting with 500 ng of total RNA, Cy3-labeled cRNA was produced according to the manufacturer's protocol. For each sample, 1.65 ug of Cy3-labeled cRNAs were fragmented and hybridized for 17 hours in a rotating hybridization oven. Slides were washed and then scanned with an Agilent Scanner.
2013-06-11 | E-GEOD-38800 | biostudies-arrayexpress
Project description:Non-steroidal anti-inflammatory drug activated gene 1 (NAG-1) plays some role in reducing obesity in mice overexpressing human NAG-1, even on a high fat diet. Male and female hNAG-1 expressing mice have reduced body weight, increased longevity and metabolic activity. This study investigates the role of hNAG-1 in female reproduction and finds that the female mice have reduced fertility and pup survival after birth. Examination of the mammary glands in these mice suggests that hNAG-1 overexpressing mice have altered mammary epithelial development during pregnancy, including reduced occupancy of the fat pad and increased apoptosis via TUNEL positive cells at lactation day 2. Pups nursing from hNAG-1 overexpressing dams have reduced milk spots compared to pups nursing from WT dams. When CD-1 pups were cross-fostered with hNAG-1 or WT dams; reduced milk volume was observed in pups nursing from hNAG-1 dams compared to pups nursing from WT dams in a lactation challenge study. Milk was isolated from WT and hNAG-1 dams, and the milk was found to have secreted NAG-1 protein (approximately 25ng/mL) from hNAG-1 dams compared to WT dams, which had no detectable NAG-1 in the milk. A decrease in non-esterified free fatty acids in the milk of hNAG-1 dams was observed. Altered milk composition suggests that the pups were receiving inadequate nutrients during perinatal development; to examine this hypothesis serum was isolated from pups and clinical chemistry points were measured. Male and female pups nursing from hNAG-1 dams had reduced serum triglyceride concentrations. Cidea/CIDEA expression was reduced in hNAG-1 mammary glands, and microarray analysis suggests that genes involved in lipid metabolism are differentially expressed in hNAG-1 mammary glands. This study suggests that overexpression of hNAG-1 impairs lactational differentiation and pup survival due to altered milk quality and quantity 4 WT mammary glands on lactation day 2 and 5 hNAG-1 transgenic mice mammary glands on lactation day 2 were used.
2015-11-10 | E-GEOD-71125 | biostudies-arrayexpress
Project description:To characterize gene expression changes in arachidonic acid metabolism pathway genes in the presense of non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) mice administered were administered an atherogenic diet for a period of four weeks. Administration of the atherogenic diet resulted in significant enrichment of the arachidonic acid metabolism pathway by gene set enrichment analysis (GSEA). The core enrichment subset of genes was down-regulated in mice administered the atherogenic diet and the majority of the genes that were down-regulated were cytochrome P450s. A total of 4 wild-type mice were administered a standard diet (STD; control group) and 4 wild-type mice were administered a HFHC diet (HFHC).
2014-01-03 | E-GEOD-53381 | biostudies-arrayexpress
Project description:Transcription of immediate early genes (IEGs) in neurons is exquisitely sensitive to neuronal activity, but the mechanism underlying the earliest of these transcription events is largely unknown. Here we demonstrate that very fast IEGs (VF-IEGs) such as arc/arg3.1 are poised for rapid transcription by the stalling of RNA Polymerase II (Pol II) just downstream of the transcription start site. RNAi-depletion of two subunits of a mediator of Pol II stalling, Negative Elongation Factor, reduces Pol II occupancy of the arc promoter and compromises rapid induction of arc and other VF-IEGs. In contrast, reduction of Pol II stalling did not prevent expression of other fast IEGs (F-IEGs). These F-IEGs are expressed with comparatively slower kinetics and largely lack promoter proximal Pol II stalling. Taken together, our data strongly indicate that very fast kinetics of neuronal IEG expression require poised Pol II and suggest a role for this mechanism in transcription-dependent learning and memory. TTX withdrawal induced neuronal activity. To study activity-induced gene expression, neurons were treated with TTX for 48 hours and then TTX was washed out either for 15 minutes (W15) or for 45 minutes (W45). Gene expression was measured in these two groups in comparison to TTX treated neurons.
2011-04-14 | E-GEOD-22622 | biostudies-arrayexpress
Project description:Gene expression analysis was conducted on lung RNA from C57BL/6J mice and compared to lung RNA from B6.129S2-Trp53tm1Ty/J mice (p53 NULL) to observe differences in baseline gene expression in mice with p53 deficiency. Lung RNA was isolated at baseline (saline airway exposure) in a total of 5 biological reps for both C57BL/6J (WT) and p53-deficient mice.
2013-04-19 | E-GEOD-38420 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-01 | E-GEOD-70196 | biostudies-arrayexpress
Project description:We used the rhesus monkey (Macaca mulatta) as our animal model for the current study with two goals: to characterize the changes in histology and gene expression from early to late gestation (prenatal uterine organogenesis) and to determine if there are effects of prenatal exposure to bisphenol A (BPA) on the developing female uterus. Pregnant rhesus monkeys carrying a female fetus (N=22) were divided into two experimental groups, based on gestational timing: 'early' (N=10) and 'late' (N=12). These groups were then equally sub-divided into control (unexposed) and BPA (exposed) groups (5 Early Control, 5 Early BPA-exposed, 6 Late Control and 6 Late BPA-exposed.) The BPA-exposed monkeys received a deuterated BPA (dBPA, CDN Isotopes, Quebec, Canada) fruit treat on a daily basis, at a dose of 400ug/kg/day). The dosing was aimed at achieving serum levels of BPA detected in adult human biomonitoring studies. The control animals received a vehicle control on a daily basis. The 'early' time period (mid-gestation) referred to gestational days 50-100, approximating the second trimester of human gestation. The fetal monkeys in the 'early' group were delivered via cesarean section on gestation day 100 and euthanized. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. The 'late' time period referred to gestational days 100-165, approximating the third trimester of human gestation. The fetal monkeys in the 'late' group were delivered vaginally and euthanized. There were five idiopathic stillbirths (2 Control, 3 BPA-exposed) in the late group. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. After delivery, the fetal uterus was excised and cut sagitally from fundus to cervix; one side was fixed for histological evaluation and the other half was frozen for analysis of gene expression by microarray. The stillbirths were excluded from the microarray.
2014-05-22 | E-GEOD-38421 | biostudies-arrayexpress
Project description:Estrogen receptor α (ERα) is a nuclear transcription factor crucial for the female reproductive function. We previously reported that mice lacking epithelial ERα in the epithelial cells of female reproductive tract (Wnt7aCre+;Esr1fl/fl, conditional knockout or cKO) were infertile, in part, due to an implantation defect. To determine if oviductal dysfunction also contributed to their infertility, we examined the fertilization rates and embryo development in vivo during the first few days of pregnancy. At 0.5 days post coitum (dpc), cKO females had significantly fewer zygotes than wild type control littermates (WT). At 1.5 dpc, cKO females had no 2-cell embryos at all; only dead oocytes or embryos and empty zona pellucidas were observed. These results indicate that lack of ERα in the oviductal epithelium resulted in alterations in the oviductal microenvironment that were detrimental to the embryos. Microarray analysis revealed dramatic differences in gene expression between cKO and WT oviducts collected at 0.5 dpc and significant but less dramatic differences at 1.5 dpc. These findings indicate that signaling via epithelial ERα is essential to generate an oviductal milieu supportive of fertilization and embryo development.and may have implications for infertility in women. The oviduct samples were collected from female reproductive tract epithelial ER α knockout (cKO) and wild type control littermates (WT) at days 1 and 2 of pregnancy (0.5 and 1.5 days post coitum). Each experimental group contains 4 replicates. Gene expression analysis was conducted by using Agilent Whole Mouse Genome 4�44 multiplex format oligo arrays (no. 014868; Agilent Technologies, Santa Clara, CA)
2015-12-08 | E-GEOD-37471 | biostudies-arrayexpress