α-SNAP regulates N-cadherin-based adherens junctions and survival of granulosa cells: insights from an in vivo model

VELASQUEZ, ZAHADY; ARCOS, ALEXIS; GIANETTI, DIEGO; TORO, GABRIELA; DE PAOLA, M. MATILDE; MICHAUT, MARCELA A.; BATIZ, LUIS F.

Puerto Varas

Congreso; Chilean Society for Cell Biology ? XXVII Annual Meeting; 2013

Introduction. Folliculogenesis is regulated by both endocrine and intra-ovarian mechanisms. Cell-cell interactions between the oocyte and granulosa cells (GC) play a key role during this process. N-cadherin-based adherens junctions (AJs) between GC are required for maturation and survival of GC. α-SNAP is a protein involved in SNARE-mediated membrane trafficking and fusion and it has recently been associated with the maintenance of cadherin-based AJs in different cell types. We investigated whether α-SNAP has a role in the cell biology and physiology of ovarian follicles using a spontaneous α-SNAP mutant mouse model known as hyh.Material and Methods. Ovaries from female wild type (WT) and hyh mice were analyzed by different microscopic and biochemical techniques. In addition, physiological studies were performed.Results. In WT animals, α-SNAP is expressed in GC and its level increases at both postpuberal stages and with exogenous gonadotrophic stimuli. On the other hand, hyh mutant females showed a reduction in ovarian α-SNAP protein levels and dramatic changes in N-cadherin-based AJs between GC. Interestingly, these changes were associated to (i) increased of apoptosis of GC, (ii) a decline in the number of viable follicles and (iii) a dramatic reduction in the ovulatory capacity and relative fecundity.Discussion. The results highlight the key role of α-SNAP in the maintenance of N-cadherin-based AJs and survival of GC during folliculogenesis. Furthermore, they suggest that defects in α-SNAP function could lead to accelerated follicular atresia and infertility.