Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparison of granulosa cells from WT and Inha KO mice following gonadotropin stimulation

ABSTRACT: Inhibin α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE20466 | GEO | 2011/02/01

SECONDARY ACCESSION(S): PRJNA125131

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Comparison of granulosa cells from WT and Inha KO mice following gonadotropin stimulation

Project description:Inhibin α knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells. (2) Genotypes (WT, Inh KO) collected from 2 preovulatory granulosa cells with and without hCG, in triplicate independent samples

2011-02-01 | E-GEOD-20466 | biostudies-arrayexpress

CNOT6/6L-mediated mRNA Degradation in Ovarian Granulosa Cells is a Key Mechanism of Gonadotropin-triggered Follicle Development

Project description:CCR4-NOT deadenylase is a major regulator of mRNA turnover in eukaryotes. It contains 2 heterogeneous catalytic subunits encoded by Cnot7/8 and Cnot6/6l genes in vertebrates, respectively. The physiological function of each catalytic subunit was unclear due to potential gene redundancy in vivo. In this study Cnot6/6l double knockout mice were generated. These mice were viable and generally healthy, but females were infertile with irregular estrus cycle and poor ovarian responses to gonadotropins. Follicle-stimulating hormone (FSH) stimulated transcription and translation of mRNAs encoding CNOT6 and CNOT6L in ovarian granulosa cells through the activity of phosphoinositide 3-kinase signaling pathway. Results of transcriptome analyses indicated that FSH downregulated a large number of transcripts in granulosa cells during the transition from pre-antral to antral follicles in a CNOT6/6L-dependent manner. These two deadenylases functioned as key effectors of FSH in altering the developmental programs in granulosa cells and triggered clearance of specific transcripts in growing follicles, particularly those encoding repressing factors of granulosa cell proliferation and steroidogenesis. These results demonstrated that FSH modulates granulosa cells function by stimulating selective translational activation and degradation of existed mRNAs, in additional to inducing de novo gene transcription. Meanwhile, this study provides in vivo evidence that CCR4-NOTCNOT6/6L-mediated mRNA deadenylation is dispensable in most somatic cell types, but is essential for the female reproductive endocrine regulation.

2021-11-04 | GSE158773 | GEO

Functional and transcriptomic dose-response analysis of follicle-stimulating hormone in ex vivo mouse folliculogenesis and oogenesis

Project description:The gonadotropin-dependent phase of ovarian folliculogenesis primarily requires follicle-stimulating hormone (FSH) to support one or multiple early antral follicles, dependent on the species, to mature fully and support steroidogenesis, oogenesis, and ovulation, which critically sustain female reproductive cycles and fertility. At molecular levels, FSH binds to its membrane receptor, FSHR, in granulosa cells to activate a suite of genes and signal transduction pathways. Both insufficient FSH caused by genetic or non-genetic reasons and excessive FSH used for ovarian stimulation in assisted reproductive technology (ART) can cause poor female reproductive outcomes, but the underlying mechanisms remain elusive. Here, we used an ex vivo folliculogenesis and oogenesis system along with single-follicle and -oocyte RNA sequencing analysis and other approaches to investigate the effects of different concentrations of FSH on key follicular events. The results revealed that a minimum FSH threshold is required for follicle maturation, and such threshold is moderately variable among individual follicles. FSH at the subthreshold, threshold, and suprathreshold levels induced distinct expression patterns of follicle maturation-related genes and the entire follicular transcriptomics. The RNA-seq analysis identified several new genes and signaling pathways that may critically regulate follicle maturation. The treatment of excessive FSH resulted in multiple ovarian disorders including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, our study enables a better understanding of the gonadotropin-dependent folliculogenesis, and the novel findings shed crucial insights into how ovarian stimulation with high doses of FSH used in ART impact follicular health, oocyte quality, pregnancy success, and systemic health.

2024-06-05 | GSE249196 | GEO

Gene expression in cultured bovine ovarian granulosa

Project description:The growth of the mammalian ovarian follicle requires the formation of a fluid filled antrum, and maturation and differentiation of the ovarian granulosa cells, largely under the control of Follicle Stimulating Hormone (FSH). Many follicles will regress and die by a process called atresia at this early antral stage. We therefore decided to analyse the gene expression profiles of granulosa cells cultured in the presence or absence of FSH and Tumour Necrosis Factor-alpha (TNF-alpha), an apoptotic factor, to simulate the key influences. Different concentratons of FSH and TNFa in granulosa culture were used to determine effective conditions via estradiol and progesterone production, and cell number. RNA for the array experiments and quantitative real time PCR was extracted from cells cultured with FSH added at 0.33 and TNF-alpha at 50 ng/ml. Four treatments of : (1) FSH alone, (2) TNF-alpha alone, (3) FSH + TNF-alpha and (4) control = neither drug, with replicates (n=4, except controls n=3 ) were used to generate RNA for the gene expression arrays (n=15)

2014-05-20 | E-GEOD-42535 | biostudies-arrayexpress

Gene expression in cultured bovine ovarian granulosa

Project description:The growth of the mammalian ovarian follicle requires the formation of a fluid filled antrum, and maturation and differentiation of the ovarian granulosa cells, largely under the control of Follicle Stimulating Hormone (FSH). Many follicles will regress and die by a process called atresia at this early antral stage. We therefore decided to analyse the gene expression profiles of granulosa cells cultured in the presence or absence of FSH and Tumour Necrosis Factor-alpha (TNFα), an apoptotic factor, to simulate the key influences. Different concentratons of FSH and TNFa in granulosa culture were used to determine effective conditions via estradiol and progesterone production, and cell number. RNA for the array experiments and quantitative real time PCR was extracted from cells cultured with FSH added at 0.33 and TNFα at 50 ng/ml.

2014-05-20 | GSE42535 | GEO

Transcription profiling of controlled ovarian hyperstimulation in human granulosa cells

Project description:The objective of this study was to investigate the differences in the gene expression profile of the granulosa cells from preovulatory follicles obtained after controlled ovarian hyperstimulation (COH) with either recombinant FSH (rFSH) or urine derived human menopausal gonadotropins (hMG).

2008-01-31 | E-MEXP-1238 | biostudies-arrayexpress

Foxo1/3 depletion in granulosa cells reveals novel mechanisms controlling follicle growth and death and endocrine regulation of pituitary FSH.

Project description:The Foxo transcription factors regulate multiple cellular functions. Foxo1 and Foxo3 are highly expressed in granulosa cells of ovarian follicles. Selective depletion of the Foxo1 and Foxo3 genes in granulosa cells revealed a novel ovarian-pituitary endocrine feedback loop characterized by: 1) undetectable levels of serum FSH but not LH, 2) reduced expression of the pituitary Fshb gene and its transcriptional regulators and 3) ovarian production of a factor(s) that suppresses pituitary cell Fshb. Equally notable and independent of FSH, depletion of Foxo1/3 altered the expression of specific genes associated with follicle growth versus apoptosis by disrupting critical regulatory interactions of Foxo1/3 with the activin and BMP2 pathways, respectively. As a consequence, granulosa cell proliferation and apoptosis were decreased. These data provide the first evidence that Foxo1/3 divergently regulate follicle growth or death by interacting with the activin and BMP pathways in granulosa cells and by modulating pituitary FSH production. A direct comparison of ovarian granulosa cells from wild type d25, Foxo1/3 dKO d25 and Foxo1/3 dKO 2 month mice.

2013-02-16 | E-GEOD-35593 | biostudies-arrayexpress

Granulosa cell expression data from five different time points before and up to 36 hours after induction of ovulation in women receiving fertility treatment

Project description:The process of ovulation includes oocyte meiotic maturation, follicle rupture and transformation of the follicle into a corpus luteum. These events are initiated by the midcycle surge of gonadotropins and require the coordinated regulation of thousands of genes. The aim of the study was to monitor the changes in granulosa cell gene expression across five different time points during the first 36 hours of ovulation until follicle rupture, in order to increase our understanding of the events of human ovulation. We conducted a prospective cohort study including women undergoing ovarian stimulation for fertility treatment. Women were treated in a standard antagonist protocol with individually dosed human menopausal gonadotropin (hMG) or recombinant follicle stimulating hormone (rFSH). Ovulation was induced with either recombinant hCG (rhCG) or gonadotropin releasing hormone agonist (GNRHa). The granulosa cells were collected by transvaginal ultrasound-guided follicle puncture of one follicle at two specific time points during ovulation (repeated measurements), and the study covered a total of five time points: before ovulation induction (OI), 12, 17, 32 and 36 hours after OI.

2020-03-01 | GSE133868 | GEO

Regulation of granulosa and theca cell transcriptomes during ovarian antral follicle development.

Project description:Coordinated interactions between ovarian granulosa and theca cells are required for female endocrine function and fertility. To elucidate these interactions the regulation of the granulosa and theca cell transcriptomes during bovine antral follicle development were investigated. Granulosa cells and theca cells were isolated from small (<5 mm), medium (5-10 mm), and large (>10 mm) antral bovine follicles. A microarray analysis of 24,000 bovine genes revealed that granulosa cells and theca cells each had gene sets specific to small, medium and large follicle cells. Transcripts regulated (i.e., minimally changed 1.5-fold) during antral follicle development for the granulosa cells involved 446 genes and for theca cells 248 genes. Only 28 regulated genes were common to both granulosa and theca cells. Regulated genes were functionally categorized with a focus on growth factors and cytokines expressed and regulated by the two cell types. Candidate regulatory growth factor proteins mediating both paracrine and autocrine cell-cell interactions include macrophage inflammatory protein (MIP1 beta), teratocarcinoma-derived growth factor 1 (TDGF1), stromal derived growth factor 1 (SDF1; i.e., CXCL12), growth differentiation factor 8 (GDF8), glia maturation factor gamma (GMFG), osteopontin (SPP1), angiopoietin 4 (ANGPT4), and chemokine ligands (CCL 2, 3, 5, and 8). The current study examined granulosa cell and theca cell regulated genes associated with bovine antral follicle development and identified candidate growth factors potentially involved in the regulation of cell-cell interactions required for ovarian function. Keywords: expression analysis, follicle assembly, ovary granulosa cell

2008-05-20 | GSE11495 | GEO

Expression data of human cumulus cells treated with follicle stimulating hormone in the presence of absence of an insulin-like growth factor 1 inhibitor

Project description:Ovulatory dysfunction affects nearly 40% of women of reproductive age that are struggling with infertility. Ovulation is the culmination of a complex and long process during which most follicles undergo atresia instead of developing into preovulatory follicles. The rescue of follicles from atresia and their maturation towards ovulatory competence requires “a pas de deux” between endocrine and locally-produced factors. Unequivocally, the most crucial endocrine factor is follicle-stimulating hormone (FSH). Insulin-like growth factors (IGFs) are among the most important local factors and are an irreplaceable partner of FSH. Therefore, understanding the mechanisms involved in the regulation of granulosa cell (GC) differentiation by FSH and IGF in humans will contribute to improve infertility treatments. In this report, we characterize a novel experimental approach to study human GC differentiation using cumulus cells from patients undergoing in vitro fertilization (IVF). Our findings demonstrate that human cumulus cells from IVF patients respond to FSH with the expression of genes that are known to be markers of granulosa cell differentiation during follicle maturation from the preantral to the large antral stage. Moreover, these results demonstrate that a large number of FSH-regulated genes require IGF1R activity and suggest that several aspects of follicle growth are coordinately regulated by FSH and the IGF system in humans. We used microarrays to detail the global effects of FSH on gene expression and to determine the effect that IGF1R inhibition has on FSH-induced stimulation.

2016-09-06 | GSE86427 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data