Association between progesterone concentration in early diestrus and endometrial gene expression in grazing dairy cows
Ontology highlight
ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE134518 | GEO | 2020/04/30
REPOSITORIES: GEO
Similar Datasets
Project description:In this study, whole transcriptome changes induced by P4 were analysed by RNAseq following laser capture microdissection (LCM) of endometrial biopsies to isolate LE, GE and ST cells. The study was performed in cows without any sign of uterine disease (as assessed by uterine cytology). At 45 days postpartum, the presence of a Corpus Luteum (CL) assessed by ultrasonography and plasma P4 concentrations were used to categorise healthy cows at 45 days postpartum determine if cows were in luteal phase (CL, P4 concentrations ≥1 ng/ml; n=4) or not (no CL, P4 concentrations < 1ng/ml; n=9). Overall, endometrial LE, GE, and ST cells shown specific transcriptomic profiles with different proportions and type of genes expressed over 10 tpm. Most of the genes differentially expressed (DEGs) in response to P4 were cell type-specific (93.9%). Genes involved in cell cycle and nuclear division were under-expressed in presence of P4 in GE and LE, highlighting the anti-proliferative action of P4 in epithelial cells. Elevated P4 concentrations were also associated with the under-expression of estrogen receptor 1 (ESR1) in GE and of oxytocin receptor (OXTR) in GE and ST. In ST, transcription factors such as SOX17 and FOXA2 , as well as interferon related genes which are known to regulate uterine epithelial–stromal crosstalk conveying to endometrial receptivity for embryo implantation, were over-expressed under P4. The results from this study show that progesterone regulates endometrial function in a cell type specific way, which looks independent of the expression of its main receptor PGR. These novel insights into uterine physiology, stand the cell compartment, rather than the whole tissue, as a physiological unit.
2021-12-03 | GSE182932 | GEO
Project description:Background: Physiological inflammation of the uterus postpartum is essential for the reparative processes of involution after calving. In the majority of cows, this inflammation is resolved and homeostasis is restored. However, in a significant subset, inflammation persists and contributes to tissue damage, pathology and subfertility. Transcriptomic differences of immune genes between cattle that resolve inflammation and those that develop uterine disease have been detected as early as 7 days postpartum (DPP) suggesting that the host immune response plays an important role in disease outcome. Results: Here, we extensively characterise the immune response at the transcriptomic level in endometrial epithelial cells from post-partum dairy cows phenotyped for both clinical and sub-clinical forms of uterine disease. We address the hypothesis that excessive expression of endometrial inflammatory molecules contributes to development of endometritis. Classification of cattle (n=112) as healthy or with uterine disease (purulent vaginal discharge; PVD and cytological endometritis; CYTO) was based on vaginal mucus score and >18% polymorphonuclear cell infiltrate into the endometrium at 21 DPP. RNA-seq analysis of endometrial epithelial cells collected using cytobrushes identified differential expression of 294 genes (FDR <0.05) between cows that subsequently resolved inflammation (n=10) and those that developed disease (n=20). Pathway over-representation analysis of differentially expressed genes (DEG) identified significant changes in immune-related pathways, including the NOD-like receptor signalling pathway, cytokine-cytokine receptor interaction pathway and the Toll-like receptor signalling pathway which were up-regulated in cattle that subsequently developed disease. The majority of the DEG were upregulated in cows that developed PVD, and included all genes upregulated in CYTO cows, suggesting a core inflammatory gene signature early post-partum contributes to the onset of uterine disease. This inflammatory signature was validated by qPCR in an independent group of cows (n=56) and included upregulation of pro-inflammatory genes (including TLR2, TLR4, NLRP3, IL1A, IL1B, IL8, and S100A8) at day 7 postpartum in cows that failed to resolve inflammation. Conclusions: Despite a large amount of inter-animal heterogeneity, these results suggest that excessive activation and inappropriate regulation of the inflammatory response early postpartum is a key feature of the subsequent development of uterine disease. Keywords: Endometritis, Inflammation, Transcriptome, Next generation sequencing, Dairy cattle, Uterine involution, Immune response
2019-04-01 | GSE125964 | GEO
Project description:Purpouse: The aim was evaluated the impact of estradiol cypionate (ECP) supplementation at the onset of a proestrus [i.e. at progesterone (P4) device removal of the synchronization of ovulation protocol] on the global endometrial gene expression of suckled anestrous beef cows Methods: A total of 12 suckled cows presenting absence of corpus luteum detected by ultrasound received 2 mg of estradiol benzoate im and an intravaginal P4 device. Eight days later, P4 devices were removed, and the cows received 500 mg of sodium cloprostenol IM. Cows were blocked according to body condition score and the diameter of largest follicle (LF) at P4 device removal and were randomly assigned to receive an im treatment with 1mg of ECP (ECP, n=6) or not (CON, n=6) at the P4 device removal. All cows received 10μg of buserelin acetate 48 h after the P4 device removal and were timed artificially inseminated immediately after. Cows presenting a new corpus luteum formed 6 d after the GnRH treatment had an endometrial fragment collected by transcervical biopsy Results: The integrated analysis was performed using DAVID database. A total of 135 transcripts were differentially expressed between ECP and CON groups, of which 73 genes were up regulated by ECP suplmentation and 62 genes in the CON cows. Two pathways were overrepresented by the ECP-induced transcripts: pathways in cancer (n=5 genes) and small cell lung cancer (n=3 genes). On the other hand, ECP-inhibited transcripts indicated the enrichment of three pathways: Parkinson’s disease (n=3 genes), oxidative phosphorylation (n=3 genes) and Alzheimer’s disease (n=3 genes). More specifically, ECP-induced transcripts associated with pathways in cancer [gene symbol (fold change); respectively] were LAMC3 (1.55), PTCH1 (1.51), PTCH2 (1.52), PIK3R3 (1.22) and PIAS1 (1.18), whereas ECP-inhibited transcripts associated with oxidative phosphorylation were ATP5F1 (1.18), ATP5J (1.24) and NDUFB3 (1.37). Conclusion: The ECP supplementation at onset of the synchronized proestrous slightly alters the uterine transcriptome.
2017-12-05 | GSE67807 | GEO
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
Project description:We investigated differential gene expression profiles of endometrium during the mid-luteal phase of the estrous cycle between repeat breeding (RB) and normally fertilized cows using microarray analysis. Caruncular (CAR) and intercaruncular (ICAR) endometrium of both ipsilateral and contralateral uterine horns to the corpus luteum were collected from RB (inseminated at least three times but not pregnant) and normally fertile cows on Day 15 of the estrous cycle. Global gene expression profiles of these endometrial samples were analyzed with a 15K custom-made oligo-microarray in cattle. Microarray analysis revealed that 405 and 397 genes were differentially expressed in CAR and ICAR of the ipsilateral uterine horn of RB, respectively when compared with normal cows. In contralateral uterine horn, 443 and 257 differentially expressed genes were identified in the CAR and ICAR of RB, respectively when compared with normal cows. In the analysis of whole uterine (combining the above four portions), RB cows showed up-regulation of 37 genes including PRSS2, GSTA3, PIPOX, CNGA1 and IGG1C and down-regulation of 39 genes including CHGA, KRT35, THBS4, CPXM2 and PRF1 compared with normal cows. Our results may suggest that local regulation of molecular mechanisms in each uterine portion contributes to normal uterine physiology.
2016-05-02 | GSE79367 | GEO
Project description:An increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers. Endometiral samples were taken from estrous synchronized beef heifers that were either cyclic or confirmed pregnant with either normal or high concentrations of progesterone on Day 5, 7, 13 and 16 of the estrous cycle/early pregnancy.
2011-10-17 | E-GEOD-33030 | biostudies-arrayexpress
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. Interrogation of the endometrial transcriptome resulted in 1,611 differentially abundant transcripts with 931 increased and 680 decreased in P4 as compared to P4+RU treated ewes.
2017-09-08 | GSE103593 | GEO
Project description:An increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers.
2011-10-18 | GSE33030 | GEO
Project description:Most dairy cows suffer uterine microbial contamination postpartum. Persistent endometritis often develops, associated with reduced fertility. We used a model of differential feeding and milking regimes to produce cows in differing negative energy balance (NEB) status in early lactation. We used Affymetrix GeneChipM-CM-^R Bovine Genome Array to investigate the global gene expression underlying negative energy balance and to identify the significantly differentially expressed genes during this process. We investigate the differences of gene expression profiles in uterine endometrial tissues between the cows with mild and severe negative energy balance.
2009-04-04 | E-GEOD-15544 | biostudies-arrayexpress
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