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Cell Death Dis ; 6: e1589, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25590799

RESUMO

Primary ovarian insufficiency (POI) is a common cause of infertility in around 1-2% of women aged <40 years. However, the mechanisms that cause POI are still poorly understood. Here we showed that germ cell-specific knockout of an essential autophagy induction gene Atg7 led to subfertility in female mice. The subfertility of Atg7 deletion females was caused by severe ovarian follicle loss, which is very similar to human POI patients. Further investigation revealed that germ cell-specific Atg7 knockout resulted in germ cell over-loss at the neonatal transition period. In addition, our in vitro studies also demonstrated that autophagy could protect oocytes from over-loss by apoptosis in neonatal ovaries under the starvation condition. Taken together, our results uncover a new role for autophagy in the regulation of ovarian primordial follicle reservation and hint that autophagy-related genes might be potential pathogenic genes to POI of women.


Assuntos
Proteínas Associadas aos Microtúbulos/deficiência , Óvulo/metabolismo , Insuficiência Ovariana Primária/metabolismo , Insuficiência Ovariana Primária/patologia , Animais , Animais Recém-Nascidos , Apoptose , Autofagia , Proteína 7 Relacionada à Autofagia , Contagem de Células , Feminino , Feto/patologia , Deleção de Genes , Humanos , Infertilidade Feminina/metabolismo , Infertilidade Feminina/patologia , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/metabolismo , Oócitos/metabolismo , Oócitos/patologia , Especificidade de Órgãos , Folículo Ovariano/embriologia , Folículo Ovariano/patologia , Óvulo/patologia
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