Document Detail


GDF9 modulates the reproductive and tumor phenotype of female inha-null mice.
MedLine Citation:
PMID:  23446452     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intraovarian factors play important roles in coordinating germ cell and somatic cell growth in the ovary. Prior to the onset of gonadotropin stimulation and reproductive cyclicity, follicle development is dependent upon locally produced growth factors, such as the transforming growth factor beta family members inhibin, activin, and GDF9. In the absence of inhibin in prepubertal mice (Inha(-/-)), there are marked alterations in preantral follicle growth, but no evidence of ovarian tumors characteristic of adult Inha-null mice. To ascertain the contribution of GDF9 to the Inha-null phenotype, we analyzed folliculogenesis in postnatal Inha Gdf9 double knockout mice. Deletion of Gdf9 from Inha(-/-) rescues the initial growth defects found at early follicle stages in Inha(-/-) ovaries, but surprisingly enhances the onset of pretumor lesions. The normalization of growth dynamics between granulosa cells and oocytes of Inha Gdf9 double knockout mice is also accompanied by a reduction in levels of the activin/inhibin beta B subunit, Inhbb, which is upregulated in Inha(-/-) ovaries. However, at later ages, Inha Gdf9 double knockout ovaries are similar to Inha(-/-) ovaries, and show upregulation of the activin/inhibin subunits and downregulation of the growth factor, kit ligand, thus resulting in a local environment that is growth-promoting for granulosa cells but growth-inhibitory for oocytes. These data suggest a sequential mechanism of action initiated by GDF9 in the Inha knockout mouse that promotes defective folliculogenesis. These studies thus provide a novel role for GDF9 in causing reproductive defects and suppressing tumor initiation in the Inha(-/-) mouse model.
Authors:
Michelle Myers; Nadera Mansouri-Attia; Rebecca James; Jia Peng; Stephanie A Pangas
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-04-04
Journal Detail:
Title:  Biology of reproduction     Volume:  88     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-05     Completed Date:  2013-11-06     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  86     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Transformation, Neoplastic / genetics
Female
Growth Differentiation Factor 9 / genetics,  metabolism,  physiology*
Inhibins / genetics*
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neoplasms / genetics*,  pathology
Organ Size
Ovarian Follicle / metabolism,  physiology
Ovary / anatomy & histology,  metabolism
Phenotype
Reproduction / genetics*
Grant Support
ID/Acronym/Agency:
R01 CA138628/CA/NCI NIH HHS; R01CA138628/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Gdf9 protein, mouse; 0/Growth Differentiation Factor 9; 0/inhibin-alpha subunit; 57285-09-3/Inhibins
Comments/Corrections

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