Impaired male fertility and abnormal epididymal epithelium differentiation in mice lacking CRISP1 and CRISP4.

CARVAJALG; BRUCKMAN NG; WEIGEL MUÑOZ M; BATTISTONE MA; GUAZZONE VANESA A.; IKAWA M; HARUHIKO M; LUSTIG L; BRETON S; CUASNICU PB

Scientific Reports

Nature Publishing Group

Año: 2018

Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with spermduring maturation and play different roles in fertilization. However, males lacking each of thesemolecules individually are fertile, suggesting compensatory mechanisms between these homologousproteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO)mice and examined their reproductive phenotype. Our data showed that the simultaneous lackof the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of theanimals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins infertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with alteredlevels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showedthat DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supportingthese defects as likely responsible for the different phenotypes observed. These observationsreveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility,contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturationand immunotolerance in the epididymis with clear implications for human epididymal physiology andpathology.