Gene expression profiling of ovaries collected from wild type (WT) mice and progesterone receptor (PR) knock out mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE37354 | GEO | 2012/10/04
SECONDARY ACCESSION(S): PRJNA159815
REPOSITORIES: GEO
Similar Datasets
Project description:Previous studies have shown that PR is a critical regulator of ovulation. The PR-null mice (PRKO) failed to ovulate due to a failure in the rupture of the preovulatory follicles. To experimentally induce ovulation, the wild type and PR null mice (C57BL/6, 24–28 d old) were injected ip with 5 IU of PMSG and 48 h later by 5 IU of hCG. Ovaries were collected at 11 h and total RNA was analyzed using Affymetrix mouse arrays
2012-10-04 | E-GEOD-37354 | biostudies-arrayexpress
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. Although PGR is not expressed in the cumulus cells or oocyte of the preovulatory cumulus oocyte complex (COC), it is well known that the COC responds to the cascade of gene expression changes that occurs in preovulatory granulosa cells. We used microarrays to identify putative ‘ovulation’ genes in preovulatory COCs at a time when PGR expression is maximal in granulosa cells (eCG + 8h hCG) and the preovulatory COC and follicle are undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92436 | GEO
Project description:Ovulation requires sequential molecular events and structural remodeling in the ovarian follicle for the successful release of a mature oocyte capable of being fertilised. Critical to this process is progesterone receptor (PGR), a transcription factor highly yet transiently expressed in granulosa cells of preovulatory follicles. Progesterone receptor knockout (PRKO) mice are anovulatory, with a specific and complete defect in follicle rupture. Therefore, this model was used to examine the critical molecular and biochemical mechanisms necessary for successful ovulation. We used microarrays to identify putative PGR-regulated genes in granulosa cells at a time when PGR expression is maximal (eCG + 8h hCG) and the preovulatory follicle is undergoing the final changes necessary for successful ovulation.
2018-04-20 | GSE92437 | GEO
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’s 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
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.
2012-08-07 | GSE39920 | GEO
Project description:Hormone receptor (HR) positive breast cancer, defined by expression of estrogen (ER) and/or progesterone (PR) receptor expression, is the most commonly diagnosed type of breast cancer. PR alters the transcriptional landscape to support tumor growth in concert with or independent of ER. Understanding the mechanisms regulating PR function are critical to developing new strategies to treat HR+ breast cancer. O-GlcNAc is a post-translational modification responsible for nutrient sensing that fine tunes protein function. We have previously reported O-GlcNAcylation on PR. Although PR is heavily post translationally modified, primarily through phosphorylation, specific sites of O-GlcNAcylation on PR, and how they regulate PR action, have not been investigated. Using established PR-expressing breast cancer cell lines, we mapped the sites of O-GlcNAcylation on PR. RNA-sequencing revealed site-specific O-GlcNAcylation of PR is critical for ligand-independent suppression of interferon signaling, a regulatory function of PR previously studied in our lab. Furthermore, O-GlcNAcylation of PR enhances PR-driven tumor growth in vivo. We have delineated one mechanism regulating PR function in breast cancer that impacts tumor growth, and provided additional insight into the mechanism through which PR attenuates interferon signaling.
2024-06-17 | MSV000095057 | MassIVE
Project description:The preovulatory luteinizing hormone surge orchestrates complex cellular and molecular events leading to ovulation. CCAAT/enhancer-binding proteins alpha and beta (C/EBPα/β) are transcription factors acutely induced by the luteinizing hormone surge and crucial for ovulation and granulosa cell luteinization. However, biological processes and their regulatory mechanisms downstream of C/EBPα/β in the preovulatory ovary are not completely understood. To address this knowledge gap, we generated Cebpa/bfl/fl;Pgr-Cre mutants and compared them with Cebpa/bfl/fl;Cyp19a1-Cre mutant female mice. The Cebpa/bfl/fl;Cyp19a1-Cre mutants have undetectable levels of C/EBPα/β throughout preovulatory stages and no ovulation, aligning with previous reports, while Cebpa/bfl/fl;Pgr-Cre mutants presented gradual deletion of C/EBPα/β during late preovulatory stage and reduced ovulation rate. Comparison of these two models indicates that sustained expression of C/EBPα/β throughout preovulatory stages is necessary for successful ovulation. This provides a unique opportunity to interrogate gene regulatory mechanisms by C/EBPα/β during different preovulatory time windows and the impact of dysregulating C/EBPα/β on ovulation-associated biological processes. Our study revealed that C/EBPα/β regulate gene expression and distinct biological functions via preovulatory stage-, dose-, and/or potentially isoform ratio- dependent mechanisms. These findings shed new light on the intricate gene regulation mechanisms by C/EBPα/β downstream of the LH surge.
2025-05-05 | GSE279171 | GEO
Project description:Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) b is highly expressed in ovarian granulosa cells and mice lacking ERb (bERKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ERb-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERb-null ovaries. ERb-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERb in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ERb-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ERb-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation We used microarray to compare the gene expression profiles of wiltype (WT) and Erb-null (bERKO) preovulatory granulosa cells as they respond to either PMSG or PMSG+hCG treatments. Laser microdissection was used to collect a purified population of granulosa cells only from preovulatory follicles. We chose to compre the response to PMSG or PMSG+hCG of granulosa cells collected from either WT and bERKO preovulatory follicles. We chose to collect cells 48h after mice were treated with PMSG to compare the gene expression profile ot preovulatory granulosa cells. We also studied the response of these cells to LH (or hCG) as we collected cells 4h after mice were treated with hCG (peak of transcriptional response to hCG).
2013-07-03 | E-GEOD-44651 | biostudies-arrayexpress
Project description:3D chromatin structure of endometrial organoids and PRKO and Sox17cKO mouse uterus
2022-05-26 | GSE200803 | GEO
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