The Granulosa Cell Response to Luteinizing Hormone is Partly Mediated by YAP1-Dependent Induction of Amphiregulin
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PROVIDER: PRJNA764441 | ENA |
REPOSITORIES: ENA
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Project description:The LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of mural granulosa and theca cells. Recently, LH-dependent activation of the Hippo signaling pathway has been shown to be required for the differentiation of granulosa cells into luteal cells. This study aimed to better characterize the role of the Hippo pathway in the LH response in murine granulosa cells. In order to highlight specific roles of Hippo in murine GC physiology, we conducted a microarray analysis to identify genes differentially expressed in cultured granulosa cells with knocked-down expression of YAP1/TAZ (the two co-regulators of Hippo signaling).
2022-01-01 | GSE184396 | GEO
Project description:BackgroundThe LH surge is a pivotal event that triggers multiple key ovarian processes including oocyte maturation, cumulus expansion, follicular wall rupture and luteinization of mural granulosa and theca cells. Recently, LH-dependent activation of the Hippo signaling pathway has been shown to be required for the differentiation of granulosa cells into luteal cells. Still, the precise interactions between Hippo and LH signaling in murine granulosa cells remain to be elucidated.MethodsTo detect the expression of effectors of the Hippo pathway, western blot, immunohistochemical and RT-qPCR analyses were performed on granulosa cells treated with LH in vitro or isolated from immature mice treated with eCG and hCG. Cultured granulosa cells were pretreated with pharmacologic inhibitors to identify the signaling pathways involved in Hippo regulation by LH. To study the roles of Yap1 and Taz in the regulation of the LH signaling cascade, RT-qPCR and microarray analyses were done on granulosa cells from Yap1f/f;Tazf/f mice treated with an adenovirus to drive cre expression. RT-qPCR was performed to evaluate YAP1 binding to the Areg promoter following chromatin immunoprecipitation of granulosa cells collected from mice prior to or 60 min following hCG treatment.ResultsGranulosa cells showed a transient increase in LATS1, YAP1 and TAZ phosphorylation levels in response to the ovulatory signal. This Hippo activation by LH was mediated by protein kinase A. Furthermore, Yap1 and Taz are required for the induction of several LH target genes such as Areg, Pgr and Ptgs2, and for the activation of the ERK1/2 pathway. Consistent with these results, there was a substantial overlap between genes that are upregulated by LH and those that are downregulated following loss of Yap1/Taz, highlighting a major role for Hippo in mediating LH actions in the ovulation process. Finally, we showed that there is a marked recruitment of YAP1 to the Areg promoter of granulosa cells in response to hCG stimulation.ConclusionsOverall, these results indicate that Hippo collaborates with the cAMP/PKA and ERK1/2 pathways to participate in the precise regulation of the LH cascade, and that Areg, as a direct transcriptional target of YAP1, is involved in mediating its actions in the ovary. Video Abstract.
| S-EPMC9137176 | biostudies-literature
Project description:Human granulosa cells are follicular cells surrounding the oocyte. Human granulosa cells are retrieved during in vitro fertilization a process where patients undergo hormonal stimulation including FSH and LH/hCG stimulation. Under the influence of the luteinizing hormone (LH) a process called luteinization they differentiate to luteal cells and contribute to the corpus luteum. Therefore, this cellular system is a good model for human corpus luteum (CL). To study processes within the human CL, IVF-derived GCs from patients were cultured for two to five days and then analyzed with mass spectrometry based shotgun proteomics.
2019-03-07 | PXD010658 | Pride
Project description:Granulosa cells from three different stages were used to assess the short- and long-term effects of luteinizing hormone (LH) on follicle differentiation: 1) 2 h before induction of the LH surge, 2) 6 h and 3) 22 h after the LH surge. Three time points experiment: 2h pre-LH, 6h post-LH and 22h post-LH. Granulosa cells from the 6h post-LH and 22h post-LH were compared to the 2h pre-LH. Biological replicates: 4 from each time point. One replicate per array. Dye-swaps were performed.
2015-05-27 | E-GEOD-69247 | biostudies-arrayexpress
Project description:Granulosa cells from three different stages were used to assess the short- and long-term effects of luteinizing hormone (LH) on follicle differentiation: 1) 2 h before induction of the LH surge, 2) 6 h and 3) 22 h after the LH surge.
2015-05-27 | GSE69247 | GEO
Project description:It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammal, however, the detail molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediates recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
2019-11-17 | GSE139663 | GEO
Project description:It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammal, however, the detail molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediates recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
2019-11-17 | GSE139664 | GEO
Project description:It is known that granulosa cells (GCs) mediate gonadotropin-induced oocyte meiosis resumption by releasing EGF-like factors in mammal, however, the detail molecular mechanisms remain unclear. Here, we demonstrate that luteinizing hormone (LH) surge induced histone deacetylase 3 (HDAC3) downregulation in GCs is essential for oocyte maturation. Before the LH surge, HDAC3 is highly expressed in GCs. Transcription factors, such as FOXO1, mediates recruitment of HDAC3 to the amphiregulin (Areg) promoter, which suppresses AREG expression. With the LH surge, decreased HDAC3 in GCs enables histone H3K14 acetylation and binding of the SP1 transcription factor to the Areg promoter to initiate AREG transcription and oocyte maturation. Conditional knockout of Hdac3 in granulosa cells in vivo or inhibition of HDAC3 activity in vitro promotes the maturation of oocytes independent of LH. Taking together, HDAC3 in GCs within ovarian follicles acts as a negative regulator of EGF-like growth factor expression before the LH surge.
2019-11-17 | GSE139665 | GEO
Project description:Comparison of global changes in ovarian transcriptomes uniquely associated with either granulosa cell tumors or luteomas, and identification of new markers for this tumor phenotype. Luteinizing hormone hypersecreting mice studied. Keywords: other
2003-07-16 | GSE499 | GEO
Project description:Comparison of global changes in ovarian transcriptomes uniquely associated with either granulosa cell tumors or luteomas, and identification of new markers for this tumor phenotype. Luteinizing hormone hypersecreting mice studied.
2007-12-13 | E-GEOD-499 | biostudies-arrayexpress