Document Detail


Targeted expression of Bcl-2 in mouse oocytes inhibits ovarian follicle atresia and prevents spontaneous and chemotherapy-induced oocyte apoptosis in vitro.
MedLine Citation:
PMID:  10379884     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Members of the Bcl-2 family serve as central checkpoints for cell death regulation, and overexpression of Bcl-2 is known to inhibit apoptosis in many cell types. To determine whether targeted expression of Bcl-2 could be used to protect female germ cells from apoptosis, we generated transgenic mice expressing fully functional human Bcl-2 protein only in oocytes. Transgenic mice were produced using a previously characterized 480-bp fragment of the mouse zona pellucida protein-3 (ZP3) gene 5'-flanking region to direct oocyte-specific expression of a human bcl-2 complementary DNA. Immunohistochemical analyses using a human Bcl-2-specific antibody showed that transgene expression was restricted to growing oocytes and was not observed in the surrounding ovarian somatic cells or in any other nonovarian tissues. Histomorphometric analyses revealed that ovaries collected from transgenic female mice possessed significantly fewer atretic small preantral follicles compared with wild-type sisters, resulting in a larger population of healthy maturing follicles per ovary. However, the number of oocytes ovulated in response to exogenous gonadotropin priming and the number of pups per litter were not significantly different among wild-type vs. transgenic female mice. Nonetheless, oocytes obtained from transgenic mice and cultured in vitro were found to be resistant to spontaneous and anticancer drug-induced apoptosis. We conclude that targeted expression of Bcl-2 only in oocytes can be achieved as a means to convey resistance of the female germ line to naturally occurring and chemotherapy-induced apoptosis.
Authors:
Y Morita; G I Perez; D V Maravei; K I Tilly; J L Tilly
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Molecular endocrinology (Baltimore, Md.)     Volume:  13     ISSN:  0888-8809     ISO Abbreviation:  Mol. Endocrinol.     Publication Date:  1999 Jun 
Date Detail:
Created Date:  1999-08-03     Completed Date:  1999-08-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8801431     Medline TA:  Mol Endocrinol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  841-50     Citation Subset:  IM    
Affiliation:
Vincent Center for Reproductive Biology, Department of Obstetrics and Gynecology, Massachusetts General Hospital/Harvard Medical School, Boston 02114, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects,  genetics*
Doxorubicin / pharmacology
Egg Proteins / genetics
Female
Follicular Atresia / genetics*
Gene Expression Regulation
Humans
Litter Size
Membrane Glycoproteins / genetics
Mice
Mice, Transgenic
Oocytes / drug effects,  metabolism*,  pathology*
Ovarian Follicle / pathology
Ovulation
Pregnancy
Proto-Oncogene Proteins c-bcl-2 / genetics*,  metabolism
Receptors, Cell Surface*
Grant Support
ID/Acronym/Agency:
R01-AG-12279/AG/NIA NIH HHS; R01-ES-08430/ES/NIEHS NIH HHS; R01-HD-34226/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Egg Proteins; 0/Membrane Glycoproteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Cell Surface; 0/zona pellucida glycoproteins; 23214-92-8/Doxorubicin

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