Document Detail

The preantral granulosa cell to cumulus cell transition in the mouse ovary: development of competence to undergo expansion.
MedLine Citation:
PMID:  16908014     Owner:  NLM     Status:  MEDLINE    
The transition of preantral to antral follicles is one of the major steps in follicular development, yet little is known about the molecular and functional changes that occur as preantral granulosa cells differentiate into cumulus cells. The cumulus oophorus of large antral follicles undergoes expansion in response to the preovulatory surge of gonadotropins, but preantral granulosa cells do not. The objective of this project was to determine the molecular mechanisms underlying this differential response. Cumulus expansion in vitro requires secretion of cumulus-expansion enabling factors (CEEFs) by the oocyte and stimulation by a ligand, epidermal growth factor (EGF) or follicle-stimulating hormone (FSH). This combined stimulation results in activation of MAPKs (MAPK3/1 (formerly ERK1/2) and MAPK14 (formerly p38)) and increased Has2, Ptgs2, Tnfaip6 and Ptx3 mRNA levels, all of which are required for cumulus expansion. Only fully-grown oocytes from antral follicles were competent to enable expansion and increases in expansion-related transcripts in cumulus cells, whereas growing oocytes of preantral follicles did not. To assess the competence of preantral granulosa cells to generate responses associated with expansion, they were treated with FSH or EGF and co-cultured with fully-grown oocytes secreting CEEFs. MAPKs were activated by EGF in preantral granulosa cells to essentially the same levels as in cumulus cells. Preantral granulosa cells treated with EGF, but not those treated with FSH increased Has2, Ptgs2 and Ptx3 mRNAs to 17-96% of the levels observed in cumulus cells. In contrast, the level of Tnfaip6 mRNA was minimally stimulated in preantral granulosa cells. Therefore, preantral granulosa cells do not undergo expansion for two fundamental reasons. First, the growing oocytes of preantral follicles do not secrete active CEEFs. Second, activation of MAPKs alone in preantral granulosa cells, even in the presence of CEEFs, is not sufficient to increase the expression of essential transcripts, particularly Tnfaip6 mRNA. Thus, preantral granulosa cells differ from cumulus cells in CEEF-dependent processes downstream of the activation of MAPKs.
F J Diaz; M J O'Brien; K Wigglesworth; J J Eppig
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-07-15
Journal Detail:
Title:  Developmental biology     Volume:  299     ISSN:  0012-1606     ISO Abbreviation:  Dev. Biol.     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-18     Completed Date:  2006-11-29     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372762     Medline TA:  Dev Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  91-104     Citation Subset:  IM    
The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609, USA.
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MeSH Terms
Cell Differentiation
Cell Proliferation
Cells, Cultured
Coculture Techniques
Enzyme Activation / drug effects
Epidermal Growth Factor / pharmacology
Follicle Stimulating Hormone / pharmacology
Gene Expression Regulation, Developmental / drug effects
Granulosa Cells / cytology*,  drug effects
Imidazoles / pharmacology
Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Models, Biological
Ovary / cytology*,  drug effects
Pyridines / pharmacology
RNA, Messenger / genetics,  metabolism
Grant Support
Reg. No./Substance:
0/Imidazoles; 0/Pyridines; 0/RNA, Messenger; 0/SB 203580; 62229-50-9/Epidermal Growth Factor; 9002-68-0/Follicle Stimulating Hormone; EC Protein Kinase 14; EC Protein Kinase 3

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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