Fertilization defects in sperm from Cysteine-Rich Secretory Protein 2 (CRISP2) 1 knockout mice: Implications for fertility disorders

BRUKMAN, NICOLÁS; MIYATA, H.; TORRES, P.; LOMBARDO, DM.; CARAMELO, J.; IKAWA, MASAITO; DA ROS, VANINA; CUASNICÚ, PATRICIA

Scientific Reports

Medip Academy

Lugar: Reino Unido; Año: 2016 p. 240 - 251

Growing evidence shows that aberrant expression of testicular Cysteine-RIch Secretory Protein 2 (CRISP2) is associated with male infertility. Based on the role of CRISP2 in fertilization, we hypothesize that mutations in Crisp2 might contribute to fertility disorders. To investigate this possibility, in the present study we generated CRISP2-deficient mice and evaluated their reproductive phenotype. Whereas fertility and in vivo fertilization rates were normal for Crisp2−/− males mated with estrus females, there was a marked reduction in fertilization levels when the animals were mated with hormone-treated females containing a higher number of eggs in the ampulla. Thus, mutant sperm have a clear deficient fertilizing ability which becomes evident only under more demanding conditions. In vitro fertilization assays using eggs surrounded or denuded of the cumulus oophorus and zona pellucida, revealed that Crisp2−/− sperm exhibited an impaired ability both to penetrate the extracellular coats and to fuse with the egg. Consistent with this, CRISP2 null sperm exhibited lower levels of hyperactivation, a vigorous motility required for penetration of the egg vestments, and an abnormal increase in intracellular Ca2+ levels after capacitation. Together, these observations support defective fertilizing ability as a mechanism underlining fertility disorders in men with aberrant expression of CRISP2. The finding that these sperm defects are masked by conventional mating studies highlights the relevance of using different experimental approaches to analyze the sperm functional state.