Document Detail


Premature luteinization and cumulus cell defects in ovarian-specific Smad4 knockout mice.
MedLine Citation:
PMID:  16513794     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
SMAD4 is a central component of the TGFbeta superfamily signaling pathway. Within the ovary, TGFbeta-related proteins play crucial roles in controlling granulosa cell growth, differentiation, and steroidogenesis. To study the in vivo roles of SMAD4 during follicle development, we generated an ovarian conditional knockout of Smad4 using the cre/loxP recombination system. Smad4 ovarian-specific knockout mice are subfertile with decreasing fertility over time and multiple defects in folliculogenesis. Regulation of steroidogenesis is disrupted in the Smad4 conditional knockout, leading to increased levels of serum progesterone. In addition, severe cumulus cell defects are present both in vivo and when assayed in vitro. These findings demonstrate that disrupting signaling through SMAD4 in the ovarian granulosa cells leads to premature luteinization of granulosa cells and eventually premature ovarian failure, thereby demonstrating key in vivo roles of TGFbeta superfamily signaling in the timing of granulosa cell differentiation.
Authors:
Stephanie A Pangas; Xiaohui Li; Elizabeth J Robertson; Martin M Matzuk
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2006-03-02
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  20     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-25     Completed Date:  2006-07-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1406-22     Citation Subset:  IM    
Affiliation:
Department of Pathology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Base Sequence
DNA Primers / genetics
Female
Granulosa Cells / pathology,  physiology
Infertility, Female / etiology
Luteinization / genetics,  physiology*
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovarian Failure, Premature / etiology
Ovary / pathology*,  physiopathology*
Ovulation / genetics,  physiology
Pregnancy
Signal Transduction
Smad4 Protein / deficiency*,  genetics,  physiology
Steroids / biosynthesis
Grant Support
ID/Acronym/Agency:
5F32HD46335/HD/NICHD NIH HHS; HD32067/HD/NICHD NIH HHS; HD44156/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/DNA Primers; 0/Smad4 Protein; 0/Smad4 protein, mouse; 0/Steroids

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


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