GnRH agonist-induced ovarian suppression and ovarian steroids in PMDD and controls
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PROVIDER: PRJNA381261 | ENA |
REPOSITORIES: ENA
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Project description:GnRH agonist-induced ovarian suppression and ovarian steroids in PMDD and controls
| PRJNA381262 | ENA
Project description:Purpose: We sought a transcriptomic analysis of endometrial tissues following GnRH agonist treatment in a mouse model Methods: The neonatal female mice were randomly divided into three groups: control group, adenomyosis group and GnRH agonist treatment group. The pregnant outcome was observed and compared among the three groups. Besides, endometrial tissues from Day 4 of pregnancy were transcriptomic analysed using bioinformatics approaches. Results:We found that the litter size was smaller in adenomyosis group than control group (8±0.28vs. 11±0.26; P＜0.05).However, the average live litter size was increased (10±0.28 vs.8±0.28; P＜0.05) after GnRH agonist treatment. Transcriptomic analysis showed that compared with the adenomyosis group, 359 genes were differentially expressed in the GnRH agonist treatment group: 218 were down regulated and 141 were up regulated.Gene function analysis showed that the differentially expressed genes were related to diverse biological processes, including estrogen metabolism, cell cycle, and metabolites biosynthesis. Conclusions: GnRH agonist can improve the pregnancy outcome of adenomyosis in mouse model. Besides pituitary down regulation effect, other possible mechanisms may play role in GnRH agonist treatment, e.g., regulate cell proliferation cycle. It may be useful for the further understand the the mechanisms of the GnRH agonist in adeomyosis treatment.
2017-06-13 | GSE89463 | GEO
Project description:Affymetrix gene expression profiling in cumulus cells (CC) retrieved from patients undergoing GnRH agonists and GnRH antagonists IVF treatment. Oocytes from three different maturity stages were considered: metaphase I oocytes (MI), nonfertilized metaphase II (MII) oocytes (MII-NF) and MII oocytes developed to blactocyst stage embryo (MII-BL). From 4 GnRH agonist treated patients, CC MI, CC MII-NF and CC MII-BL samples were collected; from 5 GnRH agonist and 6 GnRH antagonist treated patients, CC MII-NF and CC MII-BL samples were collected; and from 2 GnRH agonist and 4 GnRH antagonist treated patients, CC MI and CC MII-BL were collected. Altogether, 10 CC MI, 15 CC MII-NF and 21 CC MII-BL were collected and considered for transcriptome analysis.
2013-09-13 | E-GEOD-34230 | biostudies-arrayexpress
Project description: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.
2019-10-16 | GSE133337 | GEO
Project description:<p>In this study, lymphoblastoid cell line cultures (LCLs) from women with premenstrual dysphoric disorder (PMDD) and asymptomatic controls were compared via whole-transcriptome sequencing (RNA-seq) during untreated (ovarian steroid-free) conditions and after estradiol and progesterone treatment. In untreated LCLs, pathway analysis of the LCL transcriptome revealed, among others, over-expression of ESC/E(Z) complex genes (an ovarian steroid-regulated gene silencing complex) with significant overexpression of MTF2, PHF19, and SIRT1 (P<0.05) in cells from women with PMDD compared with controls. Finally, mRNA expression of several ESC/E(Z) complex genes were increased by progesterone in controls only, and decreased by estradiol in PMDD LCLs. </p>
| phs001344 | dbGaP
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.
2012-12-21 | E-GEOD-27467 | biostudies-arrayexpress
Project description:Administration of GnRH antagonist in IVF has several advantages. However, studies have shown that GnRH antagonist protocol cycles have lower implantation and clinical pregnancy rates than GnRH agonist long protocol cycles. Endometrial receptivity rather than embryo quality is thought to account for this phenomenon, however the mechanism is still largely unknown. This microarray analysed human endometrium during ‘implantation window phase’ between three groups: 1) untreated control, 2) GnRH agonist long protocol, and 3) GnRH antagonist protocol. The differential gene between groups uncovered the molecular mechanism occurred in endometrium affected by the intake of GnRH agonist or GnRH antagonist. Further study of these differential gene promises to find the reasons for lower endometrial receptivity in patients treated with GnRH antagonist and to improve the implantation rate in GnRH antagonist protocols in IVF.
2018-06-27 | GSE107914 | GEO
Project description:Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene cause Fragile X Syndrome, the most common monogenic cause of intellectual disability. Mutations of FMR1 are also associated with reproductive disorders, such as early cessation of reproductive function in females. While progress has been made in understanding the mechanisms of mental impairment, causes of reproductive disorders are not clear. FMR1-associated reproductive disorders were studied exclusively from the endocrine perspective, while FMR1 role in neurons that control reproduction was addressed. Here, we demonstrate that similar to women with FMR1 mutations, female Fmr1 null mice stop reproducing early. However, young null females display larger litters, more corpora lutea in the ovaries, increased inhibin, progesterone, testosterone, and gonadotropin hormones in the circulation. Given elevated ovarian hormones, increase in gonadotropins is not due to the lack of ovarian feedback, and ovariectomy reveals both hypothalamic and ovarian contribution to elevated gonadotropins. Increased vascularization of corpora lutea, higher sympathetic innervation of growing follicles in the ovaries of Fmr1 nulls, and higher numbers of synaptic GABAA receptors in GnRH neurons, which are excitatory for GnRH neurons, are also determined. Altered mRNA and protein levels of synaptic molecules in the hypothalamus are identified. Unmodified and ovariectomized Fmr1 nulls have increased LH pulse frequency, suggesting that Fmr1 nulls exhibit hyperactive GnRH neurons, regardless of ovarian feedback. These results reveal Fmr1 function in the regulation of GnRH neuron activity, and point to the role of GnRH neurons, in addition to the ovarian innervation, in the etiology of Fmr1-mediated reproductive disorders.
2023-02-13 | GSE222723 | GEO
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.
2012-12-21 | GSE27467 | GEO
Project description:The objective of this experiment was to explore differences in follicle transcriptomes in patients having oocyte maturation induced with either a bolus of hCG or a GnRH agonist. Upon oocyte retrieval, mural granuloasa cells and cumulus cells were isolated, allowing for comparison of the follicular transcriptomes between patients treated with eihter hCG or the GnHR agonist.
2013-06-15 | E-MTAB-1670 | biostudies-arrayexpress