Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens. Rat uterus mRNA of ovariectomized adult female rats subject to four different diets (Caseine, Caseine + E2, Soy and Soy+E2 ) were sequenced, in triplicate, in an Illumina GAIIx sequencer.
Project description:Chemotherapy can potentially impair fertility in premenopausal cancer patients. Female fertility preservation has been mainly focused on the ovarian aspects and benefited greatly from assisted reproductive technologies, such as in vitro fertilization (IVF). The rate-limiting step for the success of IVF is embryo implantation in the uterus. Doxorubicin (DOX) is a widely used chemotherapeutic agent with ovarian toxicity. It remains unknown if the uterus is a direct target of DOX. To circumvent the indirect uterine effect from ovarian toxicity of DOX and to investigate potential long-term impact of DOX on the uterus, young adult ovariectomized CD-1 mice were given an intraperitoneal injection once with PBS or DOX (10 mg/kg, a human relevant chemotherapeutic dose), and 30 days later, each set of mice was randomly assigned into three groups and subcutaneously injected with oil, 17β-estradiol (E2, for 6 hours), and progesterone (P4, for 54 hours), respectively. Uterine transcriptomic profiles were determined using RNA-seq. Principal component analysis of the uterine transcriptomes revealed four clusters from the six treatment groups: PBS-oil & DOX-oil, PBS-P4 & DOX-P4, PBS-E2, and DOX-E2, indicating that DOX treatment did not affect the overall uterine transcriptomic profiles in the oil and P4-treated mice but altered uterine responses to E2 treatment. These data demonstrate that DOX can directly target the uterus and has a long-term impact on uterine responses to E2.
Project description:Examination of crosstalk between Aryl hydrocarbonreceptor (AHR) and Estrogen receptor (ER) in the rat uterus on the level of mRNA transcriptome The study was designed to see the overall gene-expression change in the uterus induced by E2, the AHR ligand 3-MC alone and in combination with E2.
Project description:There are concerns regarding possible reproductive toxicity from consumption of soy including an increased risk of endometriosis and endometrial cancer. We used global uterine gene expression profiles in adult ovariectomized (OVX) female rats assessed by RNAseq to examine the estrogenicity of soy protein isolate (SPI) and the potential for feeding SPI to alter estrogen signaling in the uterus. Rats were fed AIN93G diets made with casein (CAS) or SPI from postnatal day (PND) 30. Rats were OVX on PND 50 and infused with 17 beta-estradiol (E2) or vehicle. E2 increased uterine wet weight (P<0.05) and significantly altered expression of 2084 uterine genes. In contrast, SPI feeding had no effect on uterine weight and only altered expression of 177 genes. Overlap between E2 and SPI genes was limited to 69 genes (3%). GO analysis indicated significant differences in uterine biological processes affected by E2 and SPI and little evidence for recruitment of ER alpha to the promoters of ER-responsive genes after SPI feeding. The major E2 up-regulated uterine pathways were cancer pathways and extracellular organization. SPI feeding up-regulated uterine PPAR signaling and fatty acid metabolism. The combination of E2 and SPI feeding resulted in significant regulation of 715 fewer genes relative to E2 alone. In a separate experiment, the combination of E2 and SPI reversed the ability of E2 to induce uterine proliferation in response to the carcinogen dimethybenz(a)anthracene (DMBA). These data suggest SPI does not act as a weak estrogen in the uterus but appears to be a selective estrogen receptor modulator (SERM) interacting with a small sub-set of E2-regulated genes and to be anti-estrogenic in the presence of endogenous estrogens.
Project description:Since estrogen is a major hormone involved in multiple gene expression pathways in the cell, we wanted to determine the corresponding changes in trigeminal ganglia transcriptome of the E2-treated rats. Adult ovariectomized female rats were subcutaneneously implanted with either 5% (physiological level comparable to diestrus; 15-20 pg/ml; one capsule), 20% (physiological level comparable to proestrus; 40-60 pg/ml; 2 capsules of 10%), 40% (supraphysiological level; 2 capsules of 20%) E2, or control (2 capsules of 100% cholesterol) capsules. One week after implantation, nocifensive behaviors were recorded and trigeminal ganglia tissue was extracted.
Project description:This SuperSeries is composed of the following subset Series: GSE13858: Global survey of miRNA microarray of uterus, ovariectomized female mice with or without estrogen (E2) treatment GSE13859: Global survey of miRNA microarray of whole embryo, wild type vs estrogen receptor alpha knockout mice Refer to individual Series
Project description:To evaluate the ability of a DNA binding deficient ERa to mediate transcriptional responses in the mouse uterus, ovariectomized mice were injected with 100 ul of saline or 250 ng of estradiol (E2) in 100 ul saline, uterine tissue was collected 2 hours filllowing the injection, and RNA was isolated
Project description:The ovarian hormones estrogen and progesterone orchestrate the transcriptional programs required to direct functions of the uterus for initiation and maintenance of pregnancy. Estrogen, acting via estrogen receptor alpha (ERα), regulates gene expression by activating and repressing distinct genes involved in signaling pathways that regulate cellular and physiological responses including cell division, water influx, and immune cell recruitment. Historically, these transcriptional responses have been postulated to reflect a biphasic physiological response. In this study, we explored the transcriptional responses of the ovariectomized mouse uterus to 17β-estradiol (E2) by RNA-seq to obtain global expression profiles of protein coding transcripts (mRNAs) and long noncoding RNAs (lncRNAs) following 0.5, 1, 2 and 6 hours of treatment. The E2-regulated mRNA and lncRNA expression profiles in the mouse uterus indicate an association between lncRNAs and mRNAs that regulate E2-driven pathways and reproductive phenotypes in the mouse. The transient E2-regulated transcriptome is reflected in the time-dependent shifting of biological processes regulated in the uterus in response to E2. Moreover, high expression of some conserved lncRNAs that are E2-regulated in the mouse uterus are predictive of low overall survival in endometrial carcinoma patients (e.g., H19, KCNQ1OT1, MIR17HG, and FTX). Collectively, this study (1) describes a genomic approach for identifying E2-regulated lncRNAs that may serve critical function in the uterus and (2) provides new insights into our understanding of the regulation of hormone-regulated transcriptional responses with implications in pregnancy and endometrial pathologies.