Characterization of the miRNA regulators of the human ovulatory cascade

Abstract Ovarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle...

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Autores principales: G. M. Yerushalmi, M. Salmon-Divon, L. Ophir, Y. Yung, M. Baum, G. Coticchio, R. Fadini, M. Mignini-Renzini, M. Dal Canto, R. Machtinger, E. Maman, A. Hourvitz
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Publicado: Nature Portfolio 2018
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Acceso en línea:https://doaj.org/article/327d6b3c4340443fb25cb1093138f15f
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spelling oai:doaj.org-article:327d6b3c4340443fb25cb1093138f15f2021-12-02T15:08:57ZCharacterization of the miRNA regulators of the human ovulatory cascade10.1038/s41598-018-33807-y2045-2322https://doaj.org/article/327d6b3c4340443fb25cb1093138f15f2018-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-33807-yhttps://doaj.org/toc/2045-2322Abstract Ovarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle - GV) and mature preovulatory follicles (metaphase II - M2). In this study, we performed an integrated analysis of the transcriptome and miRNome in CGCs obtained from the GV cumulus-oocyte complex (COC) obtained from IVM and M2 COC obtained from IVF. A total of 43 differentially expressed miRNAs were identified. Using Ingenuity IPA analysis, we identified 7288 potential miRNA-regulated target genes. Two hundred thirty-four of these target genes were also found in our previously generated ovulatory gene library while exhibiting anti-correlated expression to the identified miRNAs. IPA pathway analysis suggested that miR-21 and FOXM1 cooperatively inhibit CDC25A, TOP2A and PRC1. We identified a mechanism for the temporary inhibition of VEGF during ovulation by TGFB1, miR-16-5p and miR-34a-5p. The linkage bioinformatics analysis between the libraries of the coding genes from our preliminary study with the newly generated library of regulatory miRNAs provides us a comprehensive, integrated overview of the miRNA-mRNA co-regulatory networks that may play a key role in controlling post-transcriptomic regulation of the ovulatory process.G. M. YerushalmiM. Salmon-DivonL. OphirY. YungM. BaumG. CoticchioR. FadiniM. Mignini-RenziniM. Dal CantoR. MachtingerE. MamanA. HourvitzNature PortfolioarticleForkhead Box M1 (FOXM1)Cumulus Granulosa Cells (CGCs)Final Follicular MaturationOvulatory ProcessNuclear Factor Of Activated T-cells (NFAT)MedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)
institution DOAJ
collection DOAJ
language EN
topic Forkhead Box M1 (FOXM1)
Cumulus Granulosa Cells (CGCs)
Final Follicular Maturation
Ovulatory Process
Nuclear Factor Of Activated T-cells (NFAT)
Medicine
R
Science
Q
spellingShingle Forkhead Box M1 (FOXM1)
Cumulus Granulosa Cells (CGCs)
Final Follicular Maturation
Ovulatory Process
Nuclear Factor Of Activated T-cells (NFAT)
Medicine
R
Science
Q
G. M. Yerushalmi
M. Salmon-Divon
L. Ophir
Y. Yung
M. Baum
G. Coticchio
R. Fadini
M. Mignini-Renzini
M. Dal Canto
R. Machtinger
E. Maman
A. Hourvitz
Characterization of the miRNA regulators of the human ovulatory cascade
description Abstract Ovarian follicular development and ovulation are complex and tightly regulated processes that involve regulation by microRNAs (miRNAs). We previously identified differentially expressed mRNAs between human cumulus granulosa cells (CGCs) from immature early antral follicles (germinal vesicle - GV) and mature preovulatory follicles (metaphase II - M2). In this study, we performed an integrated analysis of the transcriptome and miRNome in CGCs obtained from the GV cumulus-oocyte complex (COC) obtained from IVM and M2 COC obtained from IVF. A total of 43 differentially expressed miRNAs were identified. Using Ingenuity IPA analysis, we identified 7288 potential miRNA-regulated target genes. Two hundred thirty-four of these target genes were also found in our previously generated ovulatory gene library while exhibiting anti-correlated expression to the identified miRNAs. IPA pathway analysis suggested that miR-21 and FOXM1 cooperatively inhibit CDC25A, TOP2A and PRC1. We identified a mechanism for the temporary inhibition of VEGF during ovulation by TGFB1, miR-16-5p and miR-34a-5p. The linkage bioinformatics analysis between the libraries of the coding genes from our preliminary study with the newly generated library of regulatory miRNAs provides us a comprehensive, integrated overview of the miRNA-mRNA co-regulatory networks that may play a key role in controlling post-transcriptomic regulation of the ovulatory process.
format article
author G. M. Yerushalmi
M. Salmon-Divon
L. Ophir
Y. Yung
M. Baum
G. Coticchio
R. Fadini
M. Mignini-Renzini
M. Dal Canto
R. Machtinger
E. Maman
A. Hourvitz
author_facet G. M. Yerushalmi
M. Salmon-Divon
L. Ophir
Y. Yung
M. Baum
G. Coticchio
R. Fadini
M. Mignini-Renzini
M. Dal Canto
R. Machtinger
E. Maman
A. Hourvitz
author_sort G. M. Yerushalmi
title Characterization of the miRNA regulators of the human ovulatory cascade
title_short Characterization of the miRNA regulators of the human ovulatory cascade
title_full Characterization of the miRNA regulators of the human ovulatory cascade
title_fullStr Characterization of the miRNA regulators of the human ovulatory cascade
title_full_unstemmed Characterization of the miRNA regulators of the human ovulatory cascade
title_sort characterization of the mirna regulators of the human ovulatory cascade
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/327d6b3c4340443fb25cb1093138f15f
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