Novel immunoregulatory roles for CRISP proteins within the epididymis

CARVAJAL G; BATTISTONE MA; WEIGEL MUÑOZ M; BRETON S; CUASNICÚ PS; BRUKMAN N; LUSTIG L

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC); 2016

Sociedad Argentina de Investigación Clínica (SAIC)

Epididymal CRISP1 and CRISP4 (Cysteine-Rich Secretory Proteins) associate with sperm during maturation and participate in different stages of fertilization. Whereas single knockout (KO) males for these molecules exhibit in vitro sperm fertilizing defects and normal fertility, the absence of both proteins (double KO, DKO) significantly affects both in vitro fertilization and male fertility, suggesting the existence of compensatory mechanisms between these proteins. Based on this, in the present work we investigated the mechanisms underlining the subfertility of DKO. Examination of the reproductive organs showed that 15 out of 45 DKO males had bigger caput epididymides accompanied by bigger testes. Histological studies of the epididymis of these males revealed the presence of desquamation of the epithelium, cytoplasmic vacuolation and abnormal presence of immune cells (i.e. macrophages, lymphocytes) in the interstitium and lumen mainly in the proximal regions, and damaged or no sperm in the cauda. Immunofluorescence experiments using specific markers for different epididymal epithelial cells revealed the damage and even absence of principal cells in the proximal regions of these mice. No signs of inflammation were observed in those animals with normal epididymal caput and testicular size, indicating the existence of two subgroups among the DKO mice. Interestingly, whereas the presence of the epididymal immune response positively correlated with lower sperm viability and fertility levels (p*