Document Detail


Expression and function of apoptosis initiator FOXO3 in granulosa cells during follicular atresia in pig ovaries.
MedLine Citation:
PMID:  21071886     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In mammalian ovaries, most follicles are lost by atresia before ovulation. It has become apparent that the apoptosis of granulosa cells induces follicular atresia. Forkhead box O3 (FOXO3), also called FKHRL1 (forkhead in rhabdomyosarcoma-like 1), is a proapoptotic molecule that belongs to the FOXO subfamily of forkhead transcription factors. Foxo3-deficient female mice were reported to be infertile because of abnormal ovarian follicular development, but the precise influences of FOXO3 on follicular atresia of mature ovary have not been determined. Therefore, we examined the expression and function of FOXO3 in porcine ovarian follicles and granulosa-derived cells. FOXO3 mRNA levels in granulosa cells of porcine ovaries increased during atresia, while FOXO3 protein was abundant in granulosa cells of early atretic follicles. By immunohistochemistry, the inner surface area of the granulosa layer in early atretic follicles was strongly stained with anti-FOXO3 antibody. The granulosa cells expressing FOXO3 coincided with apoptotic cells, indicating a role of FOXO3 as a proapoptotic factor in granulosa cells of porcine ovaries. In porcine (JC-410) and human (KGN) granulosa-derived cells, cell death was induced by transfection of FOXO3 expression vectors. Expression of the proapoptotic factors Fas ligand (FASLG) and BCL2-like 11 (BCL2L11) was upregulated by FOXO3 in KGN cells. In conclusion, FOXO3 is expressed in porcine ovarian follicles and induces apoptosis in granulosa cells, suggesting that it is a candidate for the initiator of follicular atresia.
Authors:
Fuko Matsuda; Naoko Inoue; Akihisa Maeda; Yuan Cheng; Takafumi Sai; Hiroshi Gonda; Yasufumi Goto; Kazuhiro Sakamaki; Noboru Manabe
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-11-06
Journal Detail:
Title:  The Journal of reproduction and development     Volume:  57     ISSN:  1348-4400     ISO Abbreviation:  J. Reprod. Dev.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-03-22     Completed Date:  2011-08-04     Revised Date:  2011-12-13    
Medline Journal Info:
Nlm Unique ID:  9438792     Medline TA:  J Reprod Dev     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  151-8     Citation Subset:  IM    
Affiliation:
Research Unit for Animal Life Sciences, Animal Resource Science Center, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Ibaraki, Japan. fukomat@yahoo.co.jp
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AB433530; RefSeq/NM_001135959
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Apoptosis*
Apoptosis Regulatory Proteins / metabolism
Cell Line
Fas Ligand Protein / metabolism
Female
Follicular Atresia / metabolism*
Forkhead Transcription Factors / chemistry,  genetics,  metabolism,  physiology*
Gene Expression Regulation*
Granulosa Cells / cytology,  metabolism*
Humans
Membrane Proteins / metabolism
Molecular Sequence Data
Organ Specificity
Ovarian Follicle / cytology,  metabolism
Protein Isoforms / genetics,  metabolism
Proto-Oncogene Proteins / metabolism
RNA, Messenger / chemistry,  metabolism
Sequence Alignment
Sequence Homology, Amino Acid
Sexual Maturation
Sus scrofa
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Bcl-2-like protein 11; 0/FOXO3 protein, human; 0/Fas Ligand Protein; 0/Forkhead Transcription Factors; 0/Membrane Proteins; 0/Protein Isoforms; 0/Proto-Oncogene Proteins; 0/RNA, Messenger

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