Expression data from progesterone receptor knockout versus heterozygous mouse oviducts
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE51499 | GEO | 2014/06/16
SECONDARY ACCESSION(S): PRJNA223321
REPOSITORIES: GEO
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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:Purpose: evaluate if different proestrus-estrus concentrations of estradiol (E2) and metestrus progesterone (P4) concentrations specifically regulate oviductal gene expression. Methods: ampulla and isthmus samples of animals whit a large pre-ovulatory follicle and a large CL (LF/LCL) and animals whit a small pre-ovulatory follicle and a small CL (SF/SCL) were collected after slaughter at day four of the estrous cycle. Total RNA was extracted and RNA sequencing was performed using the Illumina HiScanSeq (ampulla samples) and the Illumina HiSeq 2500 (isthmus samples) platforms. Results: After using HTSeq-count, approximately ~60% of the total reads uniquely mapped to the UMD 3.1 reference genome. In the ampulla samples, a total of 692 genes showed differential expression, of which 325 and 367 were up-regulated in the LF-LCL and SF-SCL samples, respectively. In the isthmus samples, a total of 590 genes showed differential expression, of which 274 and 316 were up-regulated in the isthmus of LF/LCL and SF/SCL samples, respectively. Conclusions: Our study represents the first detailed analysis of oviduct transcriptomes, generated by RNA-seq technology. Differential global gene expression profiles identified indicate that the biology of the bovine oviductal tissue is modulated by the periovulatory endocrine milieu. The LF-LCL group transcriptome may potentially reveal molecules associated with higher fertility. Oviductal mRNA profiles of cows whit different endocrine milleus were generated by next generation sequencing.
2016-06-30 | E-GEOD-65680 | biostudies-arrayexpress
Project description:Purpose: evaluate if different proestrus-estrus concentrations of estradiol (E2) and metestrus progesterone (P4) concentrations specifically regulate oviductal gene expression. Methods: ampulla and isthmus samples of animals with a large pre-ovulatory follicle and a large CL (LF/LCL) and animals with a small pre-ovulatory follicle and a small CL (SF/SCL) were collected after slaughter at day four of the estrous cycle. Total RNA was extracted and RNA sequencing was performed using the Illumina HiScanSeq (ampulla samples) and the Illumina HiSeq 2500 (isthmus samples) platforms. Results: After using HTSeq-count, approximately ~60% of the total reads uniquely mapped to the UMD 3.1 reference genome. In the ampulla samples, a total of 692 genes showed differential expression, of which 325 and 367 were up-regulated in the LF-LCL and SF-SCL samples, respectively. In the isthmus samples, a total of 590 genes showed differential expression, of which 274 and 316 were up-regulated in the isthmus of LF/LCL and SF/SCL samples, respectively. Conclusions: Our study represents the first detailed analysis of oviduct transcriptomes, generated by RNA-seq technology. Differential global gene expression profiles identified indicate that the biology of the bovine oviductal tissue is modulated by the periovulatory endocrine milieu. The LF-LCL group transcriptome may potentially reveal molecules associated with higher fertility. Oviductal mRNA profiles of cows with different endocrine milleus were generated by next generation sequencing.
2016-06-30 | E-GEOD-65679 | biostudies-arrayexpress
Project description:Progesterone (P4) is essential to prepare the endometrium for a successful pregnancy. While P4 resistance is a major cause of infertility that leads to endometrial disorders, such as endometriosis, the underlying epigenetic imbalance responsible for P4 resistance in the endometrium remains unclear. We demonstrated that CXXC finger protein 1 (CFP1), a major mediator of histone H3 lysine 4 trimethylation (H3K4m3), is an indispensable factor in the maintenance of epigenetic landscapes of P4-progesterone receptor (PGR) signaling networks in the uterus. Cfp1flox/flox;Pgr-Cre (Cfp1d/d) mice suffered from impaired P4 responses, leading to abnormal uterine cell proliferation and complete failure of embryo implantation and decidualization, albeit regular estrous cycle with normal hormone profiles. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 binding enriches promoter regions to regulate uterine mRNA landscapes not only in H3K4me3-dependent but also in H3K4me3-independent manners. Especially, CFP1 directly regulates subsets of important P4 response genes, including Gata2, Sox17, and Ihh, which mediate the activation of the smoothened signaling pathway in the uterus. P4 cannot interfere with E2 actions on uterine epithelial proliferation in Cfp1d/d mice, which was restored by supplementing a smoothened agonist (SAG). Furthermore, ectopic lesions of Cfp1d/d uterus in an endometriosis model showed P4 resistance, which was rescued by SAG. In human endometriosis, CFP1, GATA2, SOX17, and IHH, were significantly downregulated, and a positive correlation was found in the expression levels between CFP1 and these P4 targets regardless of PGR levels. Collectively, we suggest that CFP1 is an epigenetic modulator of P4-PGR signaling networks to promote uterine receptivity for embryo implantation and suppress endometriosis with P4 resistance. CFP1 is a key epigenetic factor that intervenes in the P4–epigenome–transcriptome networks for uterine function under physiologic and pathophysiologic conditions.
2023-05-10 | GSE219103 | GEO
Project description:Progesterone (P4) is essential to prepare the endometrium for a successful pregnancy. While P4 resistance is a major cause of infertility that leads to endometrial disorders, such as endometriosis, the underlying epigenetic imbalance responsible for P4 resistance in the endometrium remains unclear. We demonstrated that CXXC finger protein 1 (CFP1), a major mediator of histone H3 lysine 4 trimethylation (H3K4m3), is an indispensable factor in the maintenance of epigenetic landscapes of P4-progesterone receptor (PGR) signaling networks in the uterus. Cfp1flox/flox;Pgr-Cre (Cfp1d/d) mice suffered from impaired P4 responses, leading to abnormal uterine cell proliferation and complete failure of embryo implantation and decidualization, albeit regular estrous cycle with normal hormone profiles. mRNA and chromatin immunoprecipitation sequencing analyses showed that CFP1 binding enriches promoter regions to regulate uterine mRNA landscapes not only in H3K4me3-dependent but also in H3K4me3-independent manners. Especially, CFP1 directly regulates subsets of important P4 response genes, including Gata2, Sox17, and Ihh, which mediate the activation of the smoothened signaling pathway in the uterus. P4 cannot interfere with E2 actions on uterine epithelial proliferation in Cfp1d/d mice, which was restored by supplementing a smoothened agonist (SAG). Furthermore, ectopic lesions of Cfp1d/d uterus in an endometriosis model showed P4 resistance, which was rescued by SAG. In human endometriosis, CFP1, GATA2, SOX17, and IHH, were significantly downregulated, and a positive correlation was found in the expression levels between CFP1 and these P4 targets regardless of PGR levels. Collectively, we suggest that CFP1 is an epigenetic modulator of P4-PGR signaling networks to promote uterine receptivity for embryo implantation and suppress endometriosis with P4 resistance. CFP1 is a key epigenetic factor that intervenes in the P4–epigenome–transcriptome networks for uterine function under physiologic and pathophysiologic conditions.
2023-05-10 | GSE219102 | GEO
Project description:Purpose: evaluate if different proestrus-estrus concentrations of estradiol (E2) and metestrus progesterone (P4) concentrations specifically regulate oviductal gene expression. Methods: ampulla and isthmus samples of animals whit a large pre-ovulatory follicle and a large CL (LF/LCL) and animals whit a small pre-ovulatory follicle and a small CL (SF/SCL) were collected after slaughter at day four of the estrous cycle. Total RNA was extracted and RNA sequencing was performed using the Illumina HiScanSeq (ampulla samples) and the Illumina HiSeq 2500 (isthmus samples) platforms. Results: After using HTSeq-count, approximately ~60% of the total reads uniquely mapped to the UMD 3.1 reference genome. In the ampulla samples, a total of 692 genes showed differential expression, of which 325 and 367 were up-regulated in the LF-LCL and SF-SCL samples, respectively. In the isthmus samples, a total of 590 genes showed differential expression, of which 274 and 316 were up-regulated in the isthmus of LF/LCL and SF/SCL samples, respectively. Conclusions: Our study represents the first detailed analysis of oviduct transcriptomes, generated by RNA-seq technology. Differential global gene expression profiles identified indicate that the biology of the bovine oviductal tissue is modulated by the periovulatory endocrine milieu. The LF-LCL group transcriptome may potentially reveal molecules associated with higher fertility.
2016-06-30 | GSE65680 | GEO
Project description:Purpose: evaluate if different proestrus-estrus concentrations of estradiol (E2) and metestrus progesterone (P4) concentrations specifically regulate oviductal gene expression. Methods: ampulla and isthmus samples of animals with a large pre-ovulatory follicle and a large CL (LF/LCL) and animals with a small pre-ovulatory follicle and a small CL (SF/SCL) were collected after slaughter at day four of the estrous cycle. Total RNA was extracted and RNA sequencing was performed using the Illumina HiScanSeq (ampulla samples) and the Illumina HiSeq 2500 (isthmus samples) platforms. Results: After using HTSeq-count, approximately ~60% of the total reads uniquely mapped to the UMD 3.1 reference genome. In the ampulla samples, a total of 692 genes showed differential expression, of which 325 and 367 were up-regulated in the LF-LCL and SF-SCL samples, respectively. In the isthmus samples, a total of 590 genes showed differential expression, of which 274 and 316 were up-regulated in the isthmus of LF/LCL and SF/SCL samples, respectively. Conclusions: Our study represents the first detailed analysis of oviduct transcriptomes, generated by RNA-seq technology. Differential global gene expression profiles identified indicate that the biology of the bovine oviductal tissue is modulated by the periovulatory endocrine milieu. The LF-LCL group transcriptome may potentially reveal molecules associated with higher fertility.
2016-06-30 | GSE65679 | 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: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
Project description:The mammalian oviduct is a complex, fibromuscular organ known for its role in orchestrating a series of timely and dynamic changes to suitably support early embryogenesis. Establishing successful reproductive outcomes are largely determined through effective and cohesive communication systems between the transient embryo and the maternal environment. Climate change-induced, Heat stress (HS), is one of the largest single stressors compromising reproductive function. Systemic changes in the redox status of the maternal environment, adversely affect fertilization and early embryonic development, negative causation of HS. Oviductal organoids represent a 3-dimensional, biomimetic model to study the physiological impact of HS on the physiology of the oviduct and the subsequent developing embryo. In this study, we aimed to generate a robust bovine oviductal organoid culture system to decrypt the oviducts' differential transcriptomic response to HS, to elucidate the impact of thermal stress on oviductal physiology with subsequent potential impacts on early embryo development.
2023-10-27 | GSE221929 | GEO