Apoptotic extinction of germ cells in testes of Cyp26b1 knockout mice
| Autor: | Pierre Chambon, Martin Petkovich, Hui Li, Daniel Metzger, Glenn MacLean |
|---|---|
| Přispěvatelé: | Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
Somatic cell Drug Resistance Retinoic acid MESH: Leydig Cells Apoptosis Benzoates MESH: Mice Knockout Mice chemistry.chemical_compound 0302 clinical medicine Endocrinology Cytochrome P-450 Enzyme System Testis MESH: Animals Mice Knockout 0303 health sciences MESH: Testis MESH: Spermatozoa Leydig Cells Embryo Retinoic Acid 4-Hydroxylase Spermatozoa MESH: Tetrahydronaphthalenes 3. Good health Cell biology Meiosis MESH: Cytochrome P-450 Enzyme System MESH: Drug Resistance Germ line development Genetically modified mouse medicine.medical_specialty endocrine system Tetrahydronaphthalenes Morphogenesis Tretinoin Biology Retinoids 03 medical and health sciences MESH: Sertoli Cells Internal medicine medicine Animals MESH: Retinoids MESH: Mice 030304 developmental biology Sertoli Cells MESH: Tretinoin MESH: Apoptosis MESH: Embryo [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry Molecular Biology/Molecular biology Embryo Mammalian Embryonic stem cell MESH: Benzoates MESH: Male MESH: Meiosis chemistry Immunology 030217 neurology & neurosurgery |
| Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2007, 148 (10), pp.4560-7. ⟨10.1210/en.2007-0492⟩ |
| ISSN: | 0013-7227 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|