Membrane trafficking and adherens junctions in ovarian granulosa cells survival

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

Valdivia

Simposio; 2ND INTERNATIONAL SYMPOSIUM: Cancer and Inflammation: from adherens junctions to disease; 2015

Facultad de Ciencias, Universidad Austral de Chile

Introduction. Folliculogenesisis regulated by both endocrine and intra-ovarian mechanisms. Cell-cellinteractions between the oocyte and granulosa cells (GC) play a key role duringthis process. N-cadherin-based adherens junctions (AJs) between GC are requiredfor maturation and survival of GC. α-SNAP is a protein involved in SNARE-mediated membranetrafficking/fusion and it has recently been associated with the maintenance ofcadherin-based AJs in different cell types. We investigated whether α-SNAP has a role in the cell biology and physiology ofovarian follicles using a spontaneous α-SNAP mutant mouse model known as hyh. Material and Methods.Ovaries from female wild type (WT) and hyhmutant micewere analyzed by different microscopic and biochemical techniques. In addition,cell biology and physiological studies were performed. Results. In WT animals, α-SNAP is expressed in GC and its level increases atboth postpuberal stages and with exogenous gonadotrophic stimuli. On the otherhand, hyh mutant females showed a reduction in ovarian α-SNAP protein levels and dramatic changes inN-cadherin-based AJs between GC. Interestingly, these changes were associatedto (i) increased apoptosis of GC, (ii) a decline in the number of viablefollicles and (iii) a dramatic reduction in the ovulatory capacity and relativefecundity. Discussion. The results highlight the key role of α-SNAP in the maintenance of N-cadherin-based AJs andsurvival of GC during folliculogenesis. Furthermore, they suggest that defectsin α-SNAP function could lead toaccelerated follicular atresia and infertility.