Genome-wide analysis of gonadotropin-dependent gene expression and crosstalk of the regulatory pathways in the female ovaries
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77479 | GEO | 2016/02/03
SECONDARY ACCESSION(S): PRJNA310609
REPOSITORIES: GEO
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Project description:Effects of lack of functional LH receptor and/or a constitutively active FSH receptor on gene expression in the ovaries of female mice were studied. The results suggest that transgenic expression of the mouse Fshr in granulosa cells leads to abnormal ovarian structure/function and infertility. This finding indicates that gain-of-function mutations of the Fshr in female mice bring about distinct and clear changes in ovarian function. Total RNA was obtained from ovaries of 12 weeks old mice of different genotypes and extracted using Trizol followed by clean up with Qiage RNeasy MinElute Cleanup Kit
2016-02-03 | E-GEOD-77479 | biostudies-arrayexpress
Project description:In all vertebrates, the dual function of testis (production of sexual steroids and production of gametes) is mainly regulated by two gonadotropic pituitary hormones, FSH and LH. However, in fish the biological activities of the two hormones are not still clearly delineated and moreover, their molecular mechanisms are yet poorly understood. In this study we investigated the effects of FSH and LH on testicular gene expression, in the rainbow trout, at two developmental stages I-II and III (I: spermatogonia only, II: active spermatogonia proliferation, III: meiosis onset with the appearance of spermatocytes and round spermatids). Testes were collected from all-male population rainbow trout and incubated in six replicates for 96 hours, at 12°C, in the absence or presence of purified salmonid gonadotropins, FSH and LH (500 ng/mL).
2012-10-22 | E-GEOD-39465 | biostudies-arrayexpress
Project description:Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. The actions of human FSH and its receptor (FSHR) and mutations therein have mainly been studied using in vivo models, primary cells, cancer cells and cell lines ectopically expressing the FSHR. To allow studies of endogenous FSHR function in vitro, we differentiated FSHR-expressing cells from human pluripotent stem cells. FSH stimulation of the wild-type (WT), but not the inactivating Finnish founder mutant (A189V) receptor, activated the canonical cAMP-dependent signaling pathway and downstream mediators. Interestingly, the WT and A189V mutant receptors activated distinct pathways in a G-protein-coupled receptor signaling assay. FSH stimulation of WT FSHR-expressing cells induced phosphorylation of PI3Kp85a/g, MAPKAPK2 and proteins involved in calcium-dependent signaling, among others, while in the A189V mutant cells FSH induced phosphorylation of e.g., P90RSK, ERK3, and focal adhesion kinase. Lastly, we expressed FSHR in HEK293 cells followed by affinity purification mass spectrometry analyses, to investigate protein-protein interaction partners of FSHR at resting state and upon FSH stimulation. We found 19 specific high-confidence interacting proteins for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility. In conclusion, our protocol allows detailed studies of FSH action and disease modeling in human cells endogenously expressing FSHR.
2022-05-01 | GSE184352 | GEO
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
Project description:In all vertebrates, the dual function of testis (production of sexual steroids and production of gametes) is mainly regulated by two gonadotropic pituitary hormones, FSH and LH. However, in fish the biological activities of the two hormones are not still clearly delineated and moreover, their molecular mechanisms are yet poorly understood. In this study we investigated the effects of FSH and LH on testicular gene expression, in the rainbow trout, at two developmental stages I-II and III (I: spermatogonia only, II: active spermatogonia proliferation, III: meiosis onset with the appearance of spermatocytes and round spermatids).
2012-10-22 | GSE39465 | GEO
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.
2011-02-01 | GSE20466 | GEO
Project description:Follicle-stimulating hormone (FSH) is crucial in the development and regulation of reproductive functions. We expressed MAC-tagged FSH receptor (FSHR) in HEK293 cells followed by affinity purification mass spectrometry analyses, to investigate interactome of FSHR at resting state and upon FSH stimulation. In total, 19 specific high-confidence interactors for WT FSHR and 14 for A189V FSHR, several of which have been linked to infertility.
2021-12-17 | MSV000088577 | MassIVE
Project description:Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) b is highly expressed in ovarian granulosa cells and mice lacking ERb (bERKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ERb-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERb-null ovaries. ERb-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERb in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ERb-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ERb-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation We used microarray to compare the gene expression profiles of wiltype (WT) and Erb-null (bERKO) preovulatory granulosa cells as they respond to either PMSG or PMSG+hCG treatments. Laser microdissection was used to collect a purified population of granulosa cells only from preovulatory follicles. We chose to compre the response to PMSG or PMSG+hCG of granulosa cells collected from either WT and bERKO preovulatory follicles. We chose to collect cells 48h after mice were treated with PMSG to compare the gene expression profile ot preovulatory granulosa cells. We also studied the response of these cells to LH (or hCG) as we collected cells 4h after mice were treated with hCG (peak of transcriptional response to hCG).
2013-07-03 | E-GEOD-44651 | biostudies-arrayexpress
Project description:Effects of the absence of a functional LH receptor and/or expression of a constitutively active FSH receptor on gene expression in the gonads of male mice were studied. The results provide insights into the roles of the hormones LH and FSH in male reproduction. The main conclusion is that constant strong FSH stimulation is able to rescue the impaired spermatogenesis and fertility of male mice in the absence of LH signalling.
2016-01-20 | GSE76945 | GEO
Project description:Determining the spatial and temporal expression of genes involved in the ovulatory pathway is critical for the understanding of the role of each estrogen receptor in the modulation of folliculogenesis and ovulation. Estrogen receptor (ER) β is highly expressed in ovarian granulosa cells and mice lacking ERβ (βERKO) are subfertile due to inefficient ovulation. Previous work has focused on isolated granulosa cells or cultured follicles and while informative, provides confounding results due to the heterogeneous cell types present including granulosa, theca and oocytes and exposure to in vitro conditions. Herein, we isolated preovulatory granulosa cells from WT and ERβ-null mice using laser capture microdissection to examine the genomic transcriptional response downstream of PMSG (mimicking FSH) and PMSG/hCG (mimicking LH) stimulation. This allows for a direct comparison of in vivo granulosa cells at the same stage of development from both WT and ERβ-null ovaries. ERβ-null granulosa cells showed altered expression of genes known to be regulated by FSH (Akap12 and Runx2) as well as not previously reported (Arnt2 and Pou5f1) in WT granulosa cells. Our analysis also identified 304 genes not previously associated with ERβ in granulosa cells. LH responsive genes including Abcb1b and Fam110c show reduced expression in ERβ-null granulosa cells; however novel genes including Rassf2 and Megf10 were also identified as being downstream of LH signaling in granulosa cells. Collectively, our data suggests that granulosa cells from ERβ-null ovaries may not be appropriately differentiated and are unable to respond properly to gonadotropin stimulation We used microarray to compare the gene expression profiles of wiltype (WT) and Erb-null (bERKO) preovulatory granulosa cells as they respond to either PMSG or PMSG+hCG treatments.
2013-07-03 | GSE44651 | GEO