alpha-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.; BÁTIZ, LUIS FEDERICO

Puerto Varas

Congreso; Sociedad de Biología Celular de Chile; 2013

Sociedad de Biología Celular de Chile

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. alpha-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 alpha-SNAP has a role in the cell biology and physiology of ovarian follicles using a spontaneous alpha-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, alpha-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 alpha-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 alpha-SNAP in the maintenance of N-cadherin-based AJs and survival of GC during folliculogenesis. Furthermore, they suggest that defects in alpha-SNAP function could lead to accelerated follicular atresia and infertility.