Microcystins are produced by the cyanobacteria, most commonly Microcystis aerginosa. Upon ingestion, toxic microcystins are actively absorbed by fish, birds and mammals where they are primarily liver toxins.
No associated publication
Sex, Age, Specimen part, Compound, Time
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Constitutive expression of progesterone receptor isoforms promotes the development of hormone-dependent ovarian neoplasms.
Specimen part, Disease, Disease stage, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.
Sex, Specimen part
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A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.
Sex, Age, Specimen part, Treatment
View SamplesInfertility and adverse gynecological outcomes such as preeclampsia and miscarriage represent significant female reproductive health concerns. The spatiotemporal expression of growth factors indicates that they play an important role in pregnancy. The goal of this study is to define the role of the ERBB family of growth factor receptors in endometrial function. Using conditional ablation in mice and siRNA in primary human endometrial stromal cells, we identified the epidermal growth factor receptor (Egfr) to be critical for endometrial function during early pregnancy. While ablation of Her2 or Erbb3 led to only a modest reduction in litter size, mice lacking Egfr expression are severely subfertile. Pregnancy demise occurred shortly after blastocyst implantation due to defects in decidualization including decreased proliferation, cell survival, differentiation and target gene expression. To place Egfr in a genetic regulatory hierarchy, transcriptome analyses was used to compare the gene signatures from mice with conditional ablation of Egfr, wingless-related MMTV integration site 4 (Wnt4) or boneless morphogenic protein 2 (Bmp2); revealing that not only are Bmp2 and Wnt4 key downstream effectors of Egfr, but they also regulate distinct physiological functions. In primary human endometrial stromal cells, marker gene expression, a novel high content image-based approach and phosphokinase array analysis were used to demonstrate that EGFR is a critical regulator of human decidualization. Furthermore, inhibition of EGFR signaling intermediaries WNK1 and AKT1S1, members identified in the kinase array and previously unreported to play a role in the endometrium, also attenuate decidualization. These results demonstrate that EGFR plays an integral role in establishing the cellular context necessary for successful pregnancy via the activation of intricate signaling and transcriptional networks, thereby providing valuable insight into potential therapeutic targets.
The epidermal growth factor receptor critically regulates endometrial function during early pregnancy.
Specimen part
View SamplesThe role of Gata2 in regulating the expression of HLA in human decidual stromal cells
No associated publication
Specimen part
View SamplesAt 23 weeks old, the PGR-cre induced PGR-B constitute expression promoted the ovarian tumor progression in female mice. The transcriptomice changes can be divided into two subclass, each represented stage I and stage II ovarian tumor we observed in this study. Stage I is the early stage of ovarian tumor with small amount of PGR-B positve cells observed in the ovary but relatively normal ovarian structures. As expected, stage I transcriptome is similar to the Pgrcre/+ ovary but already exhibited 364 differentiated expression genes suggesting the early transformation of PGR-B positive cells to the neoplasma tissues. Stage II contains snumerous large pleomorphic cells, sometimes well circumscribed tumor, and most of these cells are PGR positve, but still maintains some normal ovarian functions. Stage II exibited 3129 differentiated expression genes that are involved in tumorigenesis pathways such as activated PI3K/AKT signaling, altered cell cycle pathways.
Constitutive expression of progesterone receptor isoforms promotes the development of hormone-dependent ovarian neoplasms.
Specimen part
View SamplesIndole-3-carbinol is used as a dietary supplement and has potential use as a therapeutic agent for the prevention of various types of cancer. While substantial evidence exists that indole-3-carbinol can reduce the risk of cancers induced by several known carcinogens when administered to animals, indole-3-carbinol can also function as an initiator and tumor promoter in certain models. The carcinogenic potential of indole-3-carbinol has not been studied in a 2-year bioassay. The objective of the microarray study was to evaluate the transcriptional changes in liver from rats exposed to 0 or 300 mg/kg indole-3-carbinol. At 3 months, livers were analyzed from female Harlan Sprague Dawley rats in the 2-year gavage study of indole-3-carbinol.
No associated publication
Sex, Specimen part, Compound, Time
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Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sex, Age, Specimen part, Treatment
View SamplesProgesterone (P4) signaling through its nuclear transcription factor, the progesterone receptor (PR), is essential for normal uterine function. Although deregulation of PR mediated signaling is known to underscore uterine dysfunction and a number of endometrial pathologies, the early molecular mechanisms of this deregulation are unclear. To address this issue, we have defined the genome-wide PR and GATA2 cistrome in the murine uterus using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq). In uteri of ovariectomized mice, we identified 6367 PR binding sites in the absence of P4 ligand; however, this number increased at nearly three fold (18,432) following acute P4 exposure. Sequence analysis revealed that approximately 73% of these binding sites contain a progesterone response element (PRE) or a half-site motif recognized by the PR. Many previously identified P4 target genes known to regulate uterine function were found to contain PR binding sites, confirming the validity of our methodology. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sex, Age, Specimen part
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