Document Detail

Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice.
MedLine Citation:
PMID:  17584971     Owner:  NLM     Status:  MEDLINE    
Cyp26b1 encodes a retinoic acid (RA) metabolizing cytochrome P450 enzyme that is expressed in embryonic tissues undergoing morphogenesis, including the testes. We have generated transgenic mice lacking Cyp26b1 and have observed increased RA levels in embryonic testes. Cyp26b1(-/-) germ cells prematurely enter meiosis at embryonic d 13.5 and appear to arrest at pachytene stage. Furthermore, after embryonic d 13.5, a rapid increase in apoptosis is observed in male germ cells derived from Cyp26b1(-/-) embryos; germ cells are essentially absent in mutant male neonates. In contrast, testicular somatic cells appear to develop normally in the absence of Cyp26b1. Moreover, ovarian germ and somatic cells appear unaffected by the lack of CYP26B1. We also show that the synthetic retinoid Am580, which is resistant to CYP26 metabolism, induces meiosis of male germ cells in cultured gonads, suggesting that abnormal development of germ cells in the Cyp26b1(-/-) testes results from excess RA rather than the absence of CYP26B1-generated metabolites of RA. These results provide evidence that CYP26B1 maintains low levels of RA in the developing testes that blocks entry into meiosis and acts as a survival factor to prevent apoptosis of male germ cells.
Glenn MacLean; Hui Li; Daniel Metzger; Pierre Chambon; Martin Petkovich
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-06-21
Journal Detail:
Title:  Endocrinology     Volume:  148     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-18     Completed Date:  2007-11-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4560-7     Citation Subset:  AIM; IM    
Division of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, Ontario, Canada.
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MeSH Terms
Apoptosis / drug effects,  physiology*
Benzoates / pharmacology
Cytochrome P-450 Enzyme System / deficiency*,  metabolism
Drug Resistance
Embryo, Mammalian / cytology,  metabolism
Leydig Cells / physiology
Meiosis / drug effects
Mice, Knockout
Retinoids / chemical synthesis
Sertoli Cells / physiology
Spermatozoa / physiology*,  ultrastructure
Testis / embryology*
Tetrahydronaphthalenes / pharmacology
Tretinoin / metabolism
Reg. No./Substance:
0/Benzoates; 0/Retinoids; 0/Tetrahydronaphthalenes; 102121-60-8/Am 580; 302-79-4/Tretinoin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.14.-/cytochrome P-450 CYP26B1
Comment In:
Endocrinology. 2007 Oct;148(10):4557-9   [PMID:  17876035 ]

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

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