Dataset Information

Global Long Noncoding RNA and mRNA Expression Changes between Ovarian Granulosa Cell Treatment with GnRH agonist(Alarelin) and antagonist(Cetrorelix) in goose

ABSTRACT: Gonadotropin-releasing hormone (GnRH) might combine with other reproductive hormones to affect follicular development by regulation of the cell cycle in granulosa cells (GCs).To investigate the function of GnRH in GCs, we examined the effects of a GnRH agonist (alarelin acetate) and an antagonist (cetrorelix acetate) on the proliferation of primary goose (Anser cygnoides) ovarian GCs by colorimetry and 5-ethynyl-2¢-deoxyuridine (EdU) cell proliferation assays. Differently expressed genes (DEGs) affected by these GnRH analogues in goose GCs were detected by RNA-seq and the results were verified using quantitative reverse transcription polymerase chain reaction (RT–qPCR) and western blotting. The optical densities in the colorimetry assays and the S phase cell cycle ratio of GCs in the EdU cell proliferation assays gradually increased and decreased with increasing concentrations in the alarelin-treated and cetrorelix-treated cells in dose-dependent manners, respectively. Statistically significances were achieved at concentrations of 10−5 mol/L alarelin and 1 mg/L cetrorelix acetate RNAseq analysis showed that 134 DEGs and 226 DEGs were detected following GC treatment with 10−5M GnRH alarelin (76 downregulated and 58 upregulated) and 1 mg/L cetrorelix (90 downregulated and 136 upregulated). Many of these DEGs are involved in the actions of genes encoding G protein-coupled hormone receptors, such as estrogen receptor 2 (ESR2), oxytocin receptor (OXTR), and prolactin receptor (PRLR), which are essential for folliculogenesis. The mRNA and protein expression levels of ESR2 in GCs were decreased and increased by the GnRH agonist and antagonist, respectively. Interestingly, ESR2 was increasingly expressed in pre-hierarchical follicles, most strongly expressed in GCs of F5 stage follicles and reduced in preovulatory follicles, which implicates a potential role in follicle selection. Thus, GnRH might act as an autocrine or paracrine factor to regulate GC proliferation by interacting with some key steroid hormone G protein-coupled receptors genes participating in follicular development.

ORGANISM(S): Anser cygnoides domesticus

PROVIDER: GSE133337 | GEO | 2019/10/16

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Roblitz2013 - Menstrual Cycle following GnRH analogue administration The model describes the menstrual cycle feedback mechanisms. GnRH, FSH, LH, E2, P4, inbibins A and B, and follicular development are modelled. The model predicts hormonal changes following GnRH analogue administration. Simulation results agree with measurements of hormone blood concentrations. The model gives insight into mechanisms underlying gonadotropin supression. This model is described in the article: A mathematical model of the human menstrual cycle for the administration of GnRH analogues. Röblitz S, Stötzel C, Deuflhard P, Jones HM, Azulay DO, van der Graaf PH, Martin SW. J. Theor. Biol. 2013 Mar; 321: 8-27 Abstract: The paper presents a differential equation model for the feedback mechanisms between gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), development of follicles and corpus luteum, and the production of estradiol (E2), progesterone (P4), inhibin A (IhA), and inhibin B (IhB) during the female menstrual cycle. Compared to earlier human cycle models, there are three important differences: The model presented here (a) does not involve any delay equations, (b) is based on a deterministic modeling of the GnRH pulse pattern, and (c) contains less differential equations and less parameters. These differences allow for a faster simulation and parameter identification. The focus is on modeling GnRH-receptor binding, in particular, by inclusion of a pharmacokinetic/pharmacodynamic (PK/PD) model for a GnRH agonist, Nafarelin, and a GnRH antagonist, Cetrorelix, into the menstrual cycle model. The final mathematical model describes the hormone profiles (LH, FSH, P4, E2) throughout the menstrual cycle of 12 healthy women. It correctly predicts hormonal changes following single and multiple dose administration of Nafarelin or Cetrorelix at different stages in the cycle. This model is hosted on BioModels Database and identified by: BIOMD0000000494 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Project description:The process of drinking water disinfection forms compounds known as disinfection byproducts (DBPs). Studies have shown that DBPs can be harmful to human and animal health. Iodoacetic acid (IAA) is a non-regulated DBP that is cytotoxic and genotoxic to mammalian cells. In addition, IAA has been shown to be an ovarian toxicant in vitro and in vivo. However, the mechanisms of action underlying IAA toxicity on ovarian follicles in vivo remain unclear. In this study, we determined whether IAA exposure alters gene expression patterns in ovarian antral follicles in mice. Adult female CD-1 mice were dosed with water or IAA (10 or 500mg/L) in the drinking water for 35-40 days. Antral follicles were dissected from the ovaries based on size (220–400 μm). Sera were collected to measure estradiol levels. RNA-sequencing was applied to uncover the global gene expression of the antral follicles in response to IAA exposure. RNA-sequencing analysis identified 410 and 653 differentially expressed genes (DEGs) in the 10 and 500mg/L IAA treatment groups (FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis (10mg/L) and the cell cycle, cell division, and mitotic nuclear division (500mg/L). In addition, Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B (PI3K-Akt) signaling pathway, gonadotropin-releasing hormone (GnRH) signaling pathway, estrogen signaling pathway, and insulin signaling pathway (10mg/L). In the 500mg/L group, Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis signaling pathway, GnRH signaling pathway, and oxytocin signaling pathway. In addition, RNA-sequencing analysis identified 809 DEGs when comparing the 10 and 500mg/L IAA groups (FDR < 0.1). DEGs were related to ribosome, translation, mRNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, platelet activation, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels (500mg/L) in serum compared to control. This study identified key candidate genes and pathways involved in IAA toxicity that could help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.

Project description:Purpose: Preovualtory follicle diameter influences embryo quality in beef cattle that rely on a gonadotropin releasing hormone (GnRH) injection to induce the preovualtory gonadotropin surge and subsequent ovualtion. The goals of this study are to compare transcriptome profiles of pools of four oocytes or associated cumulus cells collected from small (≤11.7mm) and large follicles (≥12.7 mm) exposed to a GnRH-induced gonadotropin surge and follicles (11.7-14.0 mm) exposed to an endogenous gonadotropin surge (spontaneous follicles). Methods: Oocyte and cumulus cell mRNA profiles of pools of four oocytes or associated cumulus cells collected from small (≤11.7mm) and large follicles (≥12.7 mm) exposed to a GnRH-induced gonadotropin surge or spontaneous follicles (11.7-14.0 mm) which were exposed to an endogenous gonadotropin surge were generated by deep sequencing (n=6 small follicle oocyte, 6 small follicle cumulus, 6 large follicle oocyte, 6 large follicle cumulus, 4 spontaneous follcile oocyte, and 5 spontaneous follicle cumulus pools), using Illumina HiSeq 2000 . The sequence reads that passed quality filters were aligned to the Bos taurus reference genome UMD3.1 using Hisat2mapper. FeatureCounts was used to quantify transcript abundance in each library using Bos taurus gene annotation from Ensembl. Differences in gene transcript expression were then analyzed amoung oocyte or cumulus cell follcile classifications using the packages edgeR and DESeq2 in R software. Results: We mapped an average of 30 million sequence reads per sample to the Bos taurus reference genome UMD3.1 and identified 69, 94, and 83 differentially expressed gene transcripts (DEG) among oocyte libraries from small versus large, small versus spontaneous, and large versus spontaneous follicle classifications, respectively. We also identified 128, 98, and 80 DEG among cumulus cell libraries from small versus large, small versus spontaneous, and large versus spontaneous follicles, respectively. Conclusions: Our study represents detailed analysis of RNA-sequencing data generated from in vivo produced cumulus and oocyte samples collected from preovualtory follicles of varied physiological status after exposure to an endogenous or exogenously stimulated gonadotropin surge. The results of our study highlight key differences in the transcriptome of samples from small, large, or spontaneous follicles and provide insight into the reduced embryo quality observed when small follicles undergo a GnRH induced gonadotropin surge.

Project description:Gonadotrophin-releasing hormone (GnRH) significantly inhibits proliferation of a proportion of cancer cell lines by activating GnRH receptor-G protein signaling. Therefore, manipulation of GnRH receptor signaling may have an under-utilized role in treating certain breast and ovarian cancers. However, the precise signaling pathways necessary for the effect and the features of cellular responses remain poorly defined. We used transcriptomic and proteomic profiling approaches to characterize the effects of GnRH receptor activation in sensitive cells (HEK293-GnRHR, SCL60) in in vitro and in vivo settings, compared to unresponsive HEK293. Analyses of gene expression demonstrated a dynamic SCL60 response to the GnRH super-agonist Triptorelin. Early and mid-phase changes (0.5-1.0 h) comprised mainly transcription factors. Later changes (8-24 h) included a GnRH target gene, CGA, and up or down-regulation of transcripts encoding signaling and cell division machinery. Pathway analysis exposed identified altered mitogen-activated protein kinase and cell cycle pathways, consistent with occurrence of G2/M arrest and apoptosis. NFκB pathway gene transcripts were differentially expressed between control and Triptorelin-treated SCL60 cultures. Reverse phase protein and phospho-proteomic array analyses profiled responses in cultured cells and SCL60 xenografts in vivo during Triptorelin anti-proliferation. Increased phosphorylated NFκB (p65) occurred in SCL60 in vitro, and p-NFκB and IκBε were higher in treated xenografts than controls after 4 days Triptorelin. NFκB inhibition enhanced the anti-proliferative effect of Triptorelin in SCL60 cultures. This study reveals details of pathways interacting with intense GnRH receptor signaling, identifies potential anti-proliferative target genes and implicates the NFκB survival pathway as a node for enhancing GnRH agonist-induced anti-proliferation. 55 samples: 35 SCL60 (15 Control, 20 Treated), 20 HEK293 (12 Control, 8 Treated). Samples collected after 0, 0.5, 1, 2, 8 or 24h after treatment with Triptorelin (100nM) or vehicle control (20% Propylene Glycol solution). SCL60 cells are HEK293 cells stably transfected with a high level of functional rat GnRHR.

Dataset Information

Global Long Noncoding RNA and mRNA Expression Changes between Ovarian Granulosa Cell Treatment with GnRH agonist(Alarelin) and antagonist(Cetrorelix) in goose

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure