M105I mutation in alpha-SNAP leads to multifactorial fertility defects in hyh female mice

DE PAOLA MM; CAPPA AI; RINALDINI E; BATIZ, LF; MICHAUT MA

Tucumán

Congreso; 3ª Reunión Conjunta de Sociedades de Biología de la República Argentina; 2015

Sociedad de Biología de Tucumán

Hydrocephalus with hop gait (hyh) is a recessive inheritable mouse disease that arose spontaneously in C57BL/10J mouse strain. A missense mutation in the gene encoding for αSNAP causes the substitution of a highly conserved Met at residue 105 for Ile (M105I). Due to αSNAP KO mice is lethal, the hyh mice provide a unique in vivo model to study αSNAP function. We previously reported that hyh male mice have a strongly reduced fertility due to a defective acrosome reaction. The aim of this work was to investigate the role of αSNAP in female fertility, focus on the oocyte and its cumulus oophurus cells (COO). After superovulation with gonadotropins, the hyh ovaries produced fewer oocytes, indicating that the function of the hyh ovary is defective. Furthermore, in vitro fertilization (IVF) rates of hyh oocytes were decreased, and polispermic rates were increased. These findings and our previous data demonstrating that αSNAP has an active role in cortical granules exocytosis (CGE), strongly suggest problems associated to this process. To gain further insight, cortical granules (CG) quantification was performed after IVF, showing a partial failure in CGE of hyh female. On the other hand, hyh mutant females showed a drastic reduction in COO αSNAP and N-cadherin protein levels, that may lead to changes in N-cadherin-based junctions between COO in the growing cumulus-oocyte complex (COC). Interestingly, these changes were associated to an increase in the apoptotic rate in COCs, assessed by TUNEL. Additionally, some hyh oocytes showed an abnormal CG polarity, suggesting that αSNAP might have a function in CG migration. Taken together, these data provide evidences showing that αSNAP plays an important role in female reproduction.