Journal article
Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction
Nature medicine, Vol.3(11), pp.1228-1232
11/1997
DOI: 10.1038/nm1197-1228
PMID: 9359697
Abstract
Female sterility resulting from oocyte destruction is an unfortunate, and in many cases inevitable, consequence of chemotherapy. We show that unfertilized mouse oocytes exposed to therapeutic levels of the antitumor drug, doxorubicin (DXR), undergo apoptosis; however, fertilized oocytes do not initiate apoptosis, but enter cell-cycle arrest, when treated with DXR. Apoptosis induced by DXR in oocytes is blocked by sphingosine-1-phosphate, an inhibitor of ceramide-promoted cell death. Oocytes from Bax-deficient, but not p53-null, female mice display complete resistance to DXR-induced apoptosis in vivo and in vitro. Pretreatment of oocytes with a specific peptide inhibitor of caspases also abrogates the apoptotic response to DXR. These findings indicate that oocyte destruction caused by chemotherapy can be prevented by manipulation of apoptosis-associated signaling pathways.
Details
- Title: Subtitle
- Apoptosis-associated signaling pathways are required for chemotherapy-mediated female germ cell destruction
- Creators
- Gloria I PerezC. Michael KnudsonLucy LeykinStanley J KorsmeyerJonathan L Tilly
- Resource Type
- Journal article
- Publication Details
- Nature medicine, Vol.3(11), pp.1228-1232
- DOI
- 10.1038/nm1197-1228
- PMID
- 9359697
- ISSN
- 1078-8956
- eISSN
- 1546-170X
- Language
- English
- Date published
- 11/1997
- Academic Unit
- Pathology; Radiation Oncology
- Record Identifier
- 9984047868602771
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