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Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes

BACKGROUND: At later stages of folliculogenesis, the mammalian ovarian follicle contains layers of epithelial granulosa cells surrounding an antral cavity. During follicle development granulosa cells replicate, secrete hormones and support the growth of the oocyte. In cattle, the follicle needs to g...

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Autores principales: Hatzirodos, Nicholas, Irving-Rodgers, Helen F, Hummitzsch, Katja, Harland, Margaret L, Morris, Stephanie E, Rodgers, Raymond J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898003/
https://www.ncbi.nlm.nih.gov/pubmed/24422759
http://dx.doi.org/10.1186/1471-2164-15-24
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author Hatzirodos, Nicholas
Irving-Rodgers, Helen F
Hummitzsch, Katja
Harland, Margaret L
Morris, Stephanie E
Rodgers, Raymond J
author_facet Hatzirodos, Nicholas
Irving-Rodgers, Helen F
Hummitzsch, Katja
Harland, Margaret L
Morris, Stephanie E
Rodgers, Raymond J
author_sort Hatzirodos, Nicholas
collection PubMed
description BACKGROUND: At later stages of folliculogenesis, the mammalian ovarian follicle contains layers of epithelial granulosa cells surrounding an antral cavity. During follicle development granulosa cells replicate, secrete hormones and support the growth of the oocyte. In cattle, the follicle needs to grow > 10 mm in diameter to allow an oocyte to ovulate, following which the granulosa cells cease dividing and differentiate into the specialised cells of the corpus luteum. To better understand the molecular basis of follicular growth and granulosa cell maturation, we undertook transcriptome profiling of granulosa cells from small (< 5 mm; n = 10) and large (> 10 mm, n = 4) healthy bovine follicles using Affymetrix microarrays (24,128 probe sets). RESULTS: Principal component analysis for the first two components and hierarchical clustering showed clustering into two groups, small and large, with the former being more heterogeneous. Size-frequency distributions of the coefficient of variation of the signal intensities of each probe set also revealed that small follicles were more heterogeneous than the large. IPA and GO enrichment analyses revealed that processes of axonal guidance, immune signalling and cell rearrangement were most affected in large follicles. The most important networks were associated with: (A) Notch, SLIT/ROBO and PI3K signalling, and (B) ITGB5 and extracellular matrix signalling through extracellular signal related kinases (ERKs). Upstream regulator genes which were predicted to be active in large follicles included STAT and XBP1. By comparison, developmental processes such as those stimulated by KIT, IHH and MEST were most active in small follicles. MGEA5 was identified as an upstream regulator in small follicles. It encodes an enzyme that modifies the activity of many target proteins, including those involved in energy sensing, by removal of N-acetylglucosamine from serine and threonine residues. CONCLUSIONS: Our data suggest that as follicles enlarge more genes and/or pathways are activated than are inactivated, and gene expression becomes more uniform. These findings could be interpreted that either the cells in large follicles are more uniform in their gene expression, or that follicles are more uniform or a combination of both and that additional factors, such as LH, are additionally controlling the granulosa cells.
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spelling pubmed-38980032014-01-23 Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes Hatzirodos, Nicholas Irving-Rodgers, Helen F Hummitzsch, Katja Harland, Margaret L Morris, Stephanie E Rodgers, Raymond J BMC Genomics Research Article BACKGROUND: At later stages of folliculogenesis, the mammalian ovarian follicle contains layers of epithelial granulosa cells surrounding an antral cavity. During follicle development granulosa cells replicate, secrete hormones and support the growth of the oocyte. In cattle, the follicle needs to grow > 10 mm in diameter to allow an oocyte to ovulate, following which the granulosa cells cease dividing and differentiate into the specialised cells of the corpus luteum. To better understand the molecular basis of follicular growth and granulosa cell maturation, we undertook transcriptome profiling of granulosa cells from small (< 5 mm; n = 10) and large (> 10 mm, n = 4) healthy bovine follicles using Affymetrix microarrays (24,128 probe sets). RESULTS: Principal component analysis for the first two components and hierarchical clustering showed clustering into two groups, small and large, with the former being more heterogeneous. Size-frequency distributions of the coefficient of variation of the signal intensities of each probe set also revealed that small follicles were more heterogeneous than the large. IPA and GO enrichment analyses revealed that processes of axonal guidance, immune signalling and cell rearrangement were most affected in large follicles. The most important networks were associated with: (A) Notch, SLIT/ROBO and PI3K signalling, and (B) ITGB5 and extracellular matrix signalling through extracellular signal related kinases (ERKs). Upstream regulator genes which were predicted to be active in large follicles included STAT and XBP1. By comparison, developmental processes such as those stimulated by KIT, IHH and MEST were most active in small follicles. MGEA5 was identified as an upstream regulator in small follicles. It encodes an enzyme that modifies the activity of many target proteins, including those involved in energy sensing, by removal of N-acetylglucosamine from serine and threonine residues. CONCLUSIONS: Our data suggest that as follicles enlarge more genes and/or pathways are activated than are inactivated, and gene expression becomes more uniform. These findings could be interpreted that either the cells in large follicles are more uniform in their gene expression, or that follicles are more uniform or a combination of both and that additional factors, such as LH, are additionally controlling the granulosa cells. BioMed Central 2014-01-14 /pmc/articles/PMC3898003/ /pubmed/24422759 http://dx.doi.org/10.1186/1471-2164-15-24 Text en Copyright © 2014 Hatzirodos et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Hatzirodos, Nicholas
Irving-Rodgers, Helen F
Hummitzsch, Katja
Harland, Margaret L
Morris, Stephanie E
Rodgers, Raymond J
Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title_full Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title_fullStr Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title_full_unstemmed Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title_short Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
title_sort transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898003/
https://www.ncbi.nlm.nih.gov/pubmed/24422759
http://dx.doi.org/10.1186/1471-2164-15-24
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