FOS, a Critical Downstream Mediator of PGR and EGF Signaling Necessary for Ovulatory Prostaglandins in the Human Ovary

Choi, Yohan; Rosewell, Katherine L.; Brännström, Mats; Akin, James W.; Curry, Thomas E.; Jo, Misung

doi:10.1210/jc.2017-02532

Cited by 45 publications

(25 citation statements)

References 39 publications

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“…Significant downregulation of three membrane‐associated transporters was confirmed in IR‐cKO mice. The hCG‐ and PGR‐dependent organic anion transporter, Slco2a1 , contributes to prostaglandin synthesis and action in granulosa cells of ovulatory follicles in humans . The zinc transporter, Slc39a14 , is expressed in cumulus granulosa cells (CGCs) and is thought to regulate free intracellular zinc in mouse oocytes .…”

Section: Resultsmentioning

confidence: 99%

“…The hCG-and PGRdependent organic anion transporter, Slco2a1, contributes to prostaglandin synthesis and action in granulosa cells of ovulatory follicles in humans. 49,50 The zinc transporter, Slc39a14, is expressed in cumulus granulosa cells (CGCs) and is thought to regulate free intracellular zinc in mouse oocytes. 51 Direct analysis of the amino acid transporter, Slc7a11, has primarily been limited to regulation of intracellular glutathione synthesis in neuronal tissue, but could play a similar role in FSH-and LH-dependent glutathione production in granulosa cells to support oocyte health.…”

Section: Ir-cko Mice Demonstrate Misregulation Of Gene Involved In mentioning

confidence: 99%

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Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility

et al. 2019

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Recent studies have demonstrated an essential role for insulin signaling in folliculogenesis as conditional ablation of Igf1r in primary follicles elicits defective follicle-stimulating hormone responsiveness blocking development at the preantral stage. Thus the potential role of insulin action in the periovulatory window and in the corpus luteum is unknown. To examine this, we generated conditional Insr, Igf1r, and double receptor knockout mice driven by Pgr-Cre. These models escape the preantral follicle block and in response to superovulatory gonadotropins exhibit normal distribution of ovarian follicles and corpora lutea. However, single ablation of Igf1r leads to subfertility and mice lacking both receptors are infertile. Double knockout mice have impaired oocyte development and ovulation. While some oocytes are released and fertilized, subsequent embryo development is retarded, and the embryos potentially fail to thrive due to lack of luteal support. In support of this, we found reduced expression of key enzymes in the steroid synthesis pathway and reduced serum progesterone. In addition to metabolic and steroidogenic pathways, RNA-sequencing analysis revealed transcription factor-3 as an important transcription factor downstream of insulin signaling. Collectively, these results highlight the importance of growth factors of the insulin family during two distinct windows of follicular development, ovulation, and luteinization. K E Y W O R D Sfemale reproduction, insulin signaling, knockout mouse, ovary | 2377 SEKULOVSKI Et aL. SUPPORTING INFORMATIONAdditional supporting information may be found online in the Supporting Information section.How to cite this article: Sekulovski N, Whorton AE, Shi M, Hayashi K, MacLean JA II. Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility. The FASEB

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Section: Resultsmentioning

confidence: 99%

Section: Ir-cko Mice Demonstrate Misregulation Of Gene Involved In mentioning

confidence: 99%

Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility

et al. 2019

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“…Interestingly, members of each of these families are strongly induced in peri-ovulatory granulosa cells and are known to participate in the ovulation pathway 39–42 . Also noteworthy are the recent findings that the RUNX transcription regulating cofactor CBFb is required for ovulatory gene expression 43 and that PGR participates in peri-ovulatory induction of with AP-1 family members Fos, JunB and JunD 44 .…”

Section: Discussionmentioning

confidence: 99%

Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression

Dinh

Breen

Akison

et al. 2019

Sci Rep

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Progesterone receptor (PGR) co-ordinately regulates ovulation, fertilisation and embryo implantation through tissue-specific actions, but the mechanisms for divergent PGR action are poorly understood. Here we characterised PGR activity in mouse granulosa cells using combined ChIP-seq for PGR and H3K27ac and gene expression microarray. Comparison of granulosa, uterus and oviduct PGR-dependent genes showed almost complete tissue specificity in PGR target gene profiles. In granulosa cells 82% of identified PGR-regulated genes bound PGR within 3 kb of the gene and PGR binding sites were highly enriched in proximal promoter regions in close proximity to H3K27ac-modified active chromatin. Motif analysis showed highly enriched PGR binding to the PGR response element (GnACAnnnTGTnC), but PGR also interacted significantly with other transcription factor binding motifs. In uterus PGR showed far more tendency to bind intergenic chromatin regions and low evidence of interaction with other transcription factors. This is the first genome-wide description of PGR action in granulosa cells and systematic comparison of diverse PGR action in different reproductive tissues. It clarifies finely-tuned contextual PGR-chromatin interactions with implications for more targeted reproductive medicine.

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“…It has been suggested that the expression of this gene drastically increases in ovulatory follicles after administration of human chorionic gonadotropin (hCG). It is one of the key ovulatory genes required to increase the level of prostaglandins (PG) during ovulation in human granulosa cells (Choi et al 2018 ). Earlier reports indicate the presence of FOS transcripts in germinal vesicles (GV) and metaphase II (MII) oocytes (Regassa et al 2011 ).…”

Section: Discussionmentioning

confidence: 99%

Genes regulating hormone stimulus and response to protein signaling revealed differential expression pattern during porcine oocyte in vitro maturation, confirmed by lipid concentration

Chermuła

Ješeta

Sujka-Kordowska

et al. 2020

Histochem Cell Biol

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Genes influencing oocyte maturation may be valuable for predicting their developmental potential, as well as discerning the mechanistic pathways regulating oocyte development. In the presented research microarray gene expression analysis of immature and in vitro matured porcine oocytes was performed. Two groups of oocytes were compared in the study: before (3 × n = 50) and after in vitro maturation (3 × n = 50). The selection of viable oocytes was performed using the brilliant cresyl blue (BCB) test. Furthermore, microarrays and RT-qPCR was used to analyze the transcriptome of the oocytes before and after IVM. The study focused on the genes undergoing differential expression in two gene-ontology groups: "Cellular response to hormone stimulus" and "Cellular response to unfolded protein", which contain genes that may directly or indirectly be involved in signal transduction during oocyte maturation. Examination of all the genes of interest showed a lower level of their expression after IVM. From the total number of genes in these gene ontologies ten of the highest change in expression were identified: FOS, ID2, BTG2, CYR61, ESR1, AR, TACR3, CCND2, EGR2 and TGFBR3. The successful maturation of the oocytes was additionally confirmed with the use of lipid droplet assay. The genes were briefly described and related to the literature sources, to investigate their potential roles in the process of oocyte maturation. The results of the study may serve as a basic molecular reference for further research aimed at improving the methods of oocyte in vitro maturation, which plays an important role in the procedures of assisted reproduction.

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FOS, a Critical Downstream Mediator of PGR and EGF Signaling Necessary for Ovulatory Prostaglandins in the Human Ovary

Abstract: The increase of FOS/activator protein 1 in human periovulatory follicles after hCG administration is mediated by collaborative actions of PGR and EGF signaling and critical for the upregulated expression of key ovulatory genes required for the rise in ovulatory PG in human granulosa cells.

Cited by 45 publications

References 39 publications

Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility

Periovulatory insulin signaling is essential for ovulation, granulosa cell differentiation, and female fertility

Tissue-specific progesterone receptor-chromatin binding and the regulation of progesterone-dependent gene expression

Genes regulating hormone stimulus and response to protein signaling revealed differential expression pattern during porcine oocyte in vitro maturation, confirmed by lipid concentration

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