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Sci Rep ; 7(1): 11765, 2017 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-28924180

RESUMO

The balance between ovarian folliculogenesis and follicular atresia is critical for female fertility and is strictly regulated by a complex network of neuroendocrine and intra-ovarian signals. Despite the numerous functions executed by granulosa cells (GCs) in ovarian physiology, the role of multifunctional proteins able to simultaneously coordinate/modulate several cellular pathways is unclear. Soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (α-SNAP) is a multifunctional protein that participates in SNARE-mediated membrane fusion events. In addition, it regulates cell-to-cell adhesion, AMPK signaling, autophagy and apoptosis in different cell types. In this study we examined the expression pattern of α-SNAP in ovarian tissue and the consequences of α-SNAP (M105I) mutation (hyh mutation) in folliculogenesis and female fertility. Our results showed that α-SNAP protein is highly expressed in GCs and its expression is modulated by gonadotropin stimuli. On the other hand, α-SNAP-mutant mice show a reduction in α-SNAP protein levels. Moreover, increased apoptosis of GCs and follicular atresia, reduced ovulation rate, and a dramatic decline in fertility is observed in α-SNAP-mutant females. In conclusion, α-SNAP plays a critical role in the balance between follicular development and atresia. Consequently, a reduction in its expression/function (M105I mutation) causes early depletion of ovarian follicles and female subfertility.


Assuntos
Fertilidade/fisiologia , Regulação da Expressão Gênica , Células da Granulosa/metabolismo , Transdução de Sinais/fisiologia , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/biossíntese , Animais , Apoptose , Adesão Celular/fisiologia , Feminino , Atresia Folicular/genética , Atresia Folicular/metabolismo , Células da Granulosa/citologia , Fusão de Membrana/fisiologia , Camundongos , Camundongos Mutantes , Mutação , Proteínas de Ligação a Fator Solúvel Sensível a N-Etilmaleimida/genética
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