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Identification of Murine Uterine Genes Regulated in a Ligand-Dependent Manner by the Progesterone Receptor.

ABSTRACT: Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology.

ORGANISM(S): Mus musculus

PROVIDER: GSE39920 | GEO | 2012/08/07

SECONDARY ACCESSION(S): PRJNA172055

REPOSITORIES: GEO

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Identification of Murine Uterine Genes Regulated in a Ligand-Dependent Manner by the Progesterone Receptor.

Project description:Progesterone (P4) acting through its cognate receptor, the progesterone receptor (PR), plays an important role in uterine physiology. The PR knockout (PRKO) mouse has demonstrated the importance of the P4-PR axis in the regulation of uterine function. To define the molecular pathways regulated by P4-PR in the mouse uterus, Affymetrix MG U74Av2 oligonucleotide arrays were used to identify alterations in gene expression after acute and chronic P4 treatments. In the analysis, retinoic acid metabolic genes, cytochrome P 450 26a1 (Cyp26a1), alcohol dehydrogenase 5, and aldehyde dehydrogenase 1a1 (Aldh1a1); kallikrein genes, Klk5 and Klk6; and specific transcription factors, GATA-2 and Cited2 [cAMP-corticosterone-binding protein/p300-interacting transactivator with glutamic acid (E) and aspartic acid (D)-rich tail], were validated as regulated by the P4-PR axis. Identification and analysis of these responsive genes will help define the role of PR in regulating uterine biology. Ovariectomized wild-type and progesterone receptor knockout mice were injected with either vehicle or 1 mg/mouse progesterone. The injections were repeated every 12 h, and groups of mice were killed 4 h after the first injection (acute P4 treatment) or 4 h after the fourth injection (chronic P4 treatment).

2012-08-06 | E-GEOD-39920 | biostudies-arrayexpress

Genome-wide Profiling of Progesterone Receptor and GATA2 Binding in the Mouse Uterus [ChIP-Seq]

Project description:Progesterone (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. Examination of PR and Gata2 binding in whole or epithelial isolated mouse uterine tissue upon acute vehicle/P4 treatement

2012-09-06 | E-GEOD-34927 | biostudies-arrayexpress

Genome-wide Profiling of Progesterone Receptor and GATA2 Binding in the Mouse Uterus [ChIP-Seq]

2012-09-06 | GSE34927 | GEO

Genome-wide Profiling of Progesterone Receptor and GATA2 Binding in the Mouse Uterus [Affymetrix]

2012-09-06 | GSE34902 | GEO

Genome-wide Profiling of Progesterone Receptor and GATA2 Binding in the Mouse Uterus [Affymetrix]

Project description:Progesterone (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. Gene expression data from ovariectomized Oil and P4 treated Gata2 f/f uterus horn

2012-09-06 | E-GEOD-34902 | biostudies-arrayexpress

Gata2 is a master regulator of endometrial function and progesterone signaling [ChIP-Seq]

Project description:The role of Gata2 in regulating uterine function including fertility, implantation, decidualization and P4 signaling in the mouse was investigated by the conditional ablation of Gata2 in the uterus using the (PR-cre) mouse and ChIP-seq for in vivo GATA2 binding sites in the murine uterus upon acute P4 administration. Gata2 gene ablation was confirmed by real-time PCR analysis in the PR-cre; Gata2fl/fl (termed Gata2d/d) uterus. While littermate controls are fertile, Gata2d/d females are completely infertile. Analysis of the infertility indicates that implantation does not occur, and the uterine stroma is incapable of undergoing the decidual reaction to support further embryonic development. Measure of P4 target genes including PR itself indicate a block in P4 target gene induction and that Gata2 regulates PR expression directly. Microarray analysis demonstrates that ablation of Gata2 leads to specific gene changes, including disruption of the Wnt signaling pathway, Progesterone receptor (PR) signaling, and Ihh signaling pathway. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.Taken together, these data demonstrate that Gata2 is a critical regulator of gene expression and function in the murine uterus.

2014-01-01 | E-GEOD-40659 | biostudies-arrayexpress

Gata2 is a master regulator of endometrial function and progesterone signaling [Affymetrix]

2014-01-01 | E-GEOD-40660 | biostudies-arrayexpress

Expression data from progesterone receptor knockout versus heterozygous mouse oviducts

Project description:The oviducts play a critical role in gamete and embryo transport, as well as supporting fertilization and early embryo development. Progesterone receptor (PGR) is a transcription factor highly expressed in oviductal cells, while it‚Äôs activating ligand, progesterone (P4), surges to peak levels as ovulation approaches. P4 is known to regulate oviduct cilia beating and muscular contractions in vitro, but how PGR may mediate this in vivo is poorly understood. We used PGR-knockout (PRKO) mice to determine how PGR regulates oviductal function during the periovulatory period, in particular oviductal transport and embryo support. We used microarrays to identify putative PGR-regulated genes in the oviduct during the periovulatory period, a time when the oviduct is preparing to receive the newly-ovulated COC. The mutant strain used in this experiment were PRlacZ knock-in mice which originated from Assoc Prof John Lydon, Baylor College of Medicine, Houston TX, USA. The lacZ insertion results in disruption of transcription of both isoforms of PGR (Ismail et al, 2002, Mol Endocrinol 16:2475-2489), and therefore mice homozygous for the lacZ insertion are a phenocopy of the knockout strain described by Lydon et al. (1995, Genes Dev. 9:2266-2278) and are hereafter referred to as PRKO. Heterozygous mice (PR+/-) are a phenocopy of WT and have normal fertility (Ismail et al, 2002) and are therefore appropriate controls. Whole oviducts were collected from pre-pubertal PRKO and PR+/- mice 8 h after a standard protocol for hormonal induction of ovulation. Day 21-23 old mice were injected i.p. with 5IU of equine chorionic gonadotropin (eCG) to stimulate follicle growth, followed 44-47 h later by i.p. injection of 5 IU of human chorionic gonadotropin (hCG) to trigger ovulatory processes. Oviducts from 15 animals were collected per genotype, with oviducts from 3 animals pooled per sample for a total of n = 5 samples per genotype.

2014-06-16 | E-GEOD-51499 | biostudies-arrayexpress

Hormone-responsive organoid cultures of human endometrium

Project description:The aim of the experiment was to investigate the effects of stimulation of human endometrial organoids with estrogen (E2) and progesterone (P4) In humans, the endometrium, the uterine mucosal lining, undergoes dynamic changes throughout the menstrual cycle and in pregnancy. We adapted conditions used to establish human adult stem cell-derived organoid cultures to generate 3D cultures of human endometrium. Unlike other mucosal epithelia, the endometrium responds dramatically to ovarian sex hormones, estrogen (E2) and progesterone (P4), which regulate cyclical proliferation and differentiation of endometrial glands with concomitant dynamic temporal and spatial expression of their receptors, ERalpha and PR.

2017-04-11 | GSE94723 | GEO

Progesterone Regulation of Extracellular Vesicles in the Uterine Luminal Fluid of Sheep (miRNA-Seq)

Project description:Progesterone (P4) acts via the endometrium to modify the uterine environment and promotes conceptus growth for elongation and pregnancy establishment. Ewes were ovariectomized and treated with P4 for 14 days or P4 for 14 days and RU486, a progesterone receptor antagonist, from days 8 to 14. Small RNA sequencing of endometrium and EVs from the uterine lumen detected expression of 768 miRNAs and P4 regulation of 9 endometrial and 7 extracellular vesicle miRNAs.

2017-09-08 | GSE103595 | GEO

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