Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 2 de 2
Filtrar
Más filtros

Banco de datos
Tipo de estudio
Tipo del documento
País de afiliación
Intervalo de año de publicación
1.
Dev Biol ; 331(2): 292-9, 2009 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-19447101

RESUMEN

In mammals, primordial follicles are generated early in life and remain dormant for prolonged intervals. Their growth resumes via a process known as primordial follicle activation. Recent genetic studies have demonstrated that phosphoinositide 3-kinase (PI3K) is the essential signaling pathway controlling this process throughout life, acting via Akt to regulate nucleocytoplasmic shuttling of Foxo3, which functions as a downstream molecular switch. The receptor tyrosine kinase Kit has been implicated by numerous studies as the critical upstream regulator of primordial follicle activation via PI3K/Akt. Here we present a genetic analysis of the contribution of Kit in regulating primordial follicle activation and early follicle growth, employing a knock-in mutation (Kit(Y719F)) that completely abrogates signaling via PI3K. Surprisingly, homozygous Kit(Y719F) female mice undergo primordial follicle activation and are fertile, demonstrating that Kit signaling via PI3K is dispensable for this process. However, other abnormalities were identified in Kit(Y719F) ovaries, including accelerated primordial follicle depletion and accumulation of morphologically abnormal primary/secondary follicles with persistent nuclear Foxo3 localization. These findings reveal specific roles of Kit in the maintenance of the primordial follicle reserve and in the primary to secondary follicle transition, but argue that Kit is dispensable in primordial follicle activation.


Asunto(s)
Folículo Ovárico/fisiología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-kit/fisiología , Transducción de Señal/fisiología , Animales , Animales Recién Nacidos , Femenino , Técnicas de Sustitución del Gen , Ratones , Mutación , Folículo Ovárico/citología , Ovario/citología , Ovario/crecimiento & desarrollo , Ovario/fisiología , Proteínas Proto-Oncogénicas c-kit/genética
2.
Genetics ; 177(1): 179-94, 2007 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-17660561

RESUMEN

Female infertility syndromes are among the most prevalent chronic health disorders in women, but their genetic basis remains unknown because of uncertainty regarding the number and identity of ovarian factors controlling the assembly, preservation, and maturation of ovarian follicles. To systematically discover ovarian fertility genes en masse, we employed a mouse model (Foxo3) in which follicles are assembled normally but then undergo synchronous activation. We developed a microarray-based approach for the systematic discovery of tissue-specific genes and, by applying it to Foxo3 ovaries and other samples, defined a surprisingly large set of ovarian factors (n = 348, approximately 1% of the mouse genome). This set included the vast majority of known ovarian factors, 44% of which when mutated produce female sterility phenotypes, but most were novel. Comparative profiling of other tissues, including microdissected oocytes and somatic cells, revealed distinct gene classes and provided new insights into oogenesis and ovarian function, demonstrating the utility of our approach for tissue-specific gene discovery. This study will thus facilitate comprehensive analyses of follicle development, ovarian function, and female infertility.


Asunto(s)
Factores de Transcripción Forkhead/fisiología , Genes/fisiología , Genoma , Infertilidad Femenina/metabolismo , Folículo Ovárico/fisiología , Animales , Northern Blotting , Femenino , Proteína Forkhead Box O3 , Factores de Transcripción Forkhead/genética , Perfilación de la Expresión Génica , Hibridación in Situ , Infertilidad Femenina/patología , Rayos Láser , Meiosis , Ciclo Menstrual , Ratones , Ratones Noqueados , Microdisección , Análisis de Secuencia por Matrices de Oligonucleótidos , Oocitos/fisiología , Oocitos/ultraestructura , Oogénesis/fisiología , Folículo Ovárico/ultraestructura , Sondas ARN , ARN Mensajero/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA