Influence of the genetic background on the reproductive phenotype of mice lacking Cysteine-RIch Secretory Protein 1 (CRISP1)

BATTISTONE, MA.; CURSI,L.; PIGNATARO, OP.; WEIGEL MUÑOZ, M.; MALDERA, JA.; LOMBARDO, DM.; CUASNICÚ, PATRICIA; WEIGEL MUÑOZ, M.; MALDERA, JA.; LOMBARDO, DM.; CUASNICÚ, PATRICIA; CARVAJAL, G.; TORRES, P.; DA ROS, VANINA; CARVAJAL, G.; TORRES, P.; DA ROS, VANINA; BATTISTONE, MA.; CURSI,L.; PIGNATARO, OP.

BIOLOGY OF REPRODUCTION

SOC STUDY REPRODUCTION

Año: 2018 p. 373 - 383

0006-3363

Sperm epididymal protein CRISP1 regulates murine CatSper, the main sperm calcium channel,and participates in different stages of fertilization. In spite of its relevance for sperm function, Crisp1-/- mice are fertile. Considering that phenotypes can be influenced by the genetic background, in the present work mice from the original mixed Crisp1-/- colony (129/SvEv*C57BL/6N) were backcrossed onto the C57BL/6 strain for subsequent analysis of their reproductive phenotype. Whereas fertility and fertilization rates of C57BL/6 Crisp1-/-males did not differ from those reported for mice from the mixed background, several spermfunctional parameters were clearly affected by the genetic background. Crisp1-/-sperm from the homogeneous background exhibited defects in both the progesterone-induced acrosome reaction and sperm motility not observed in the mixed background and normal rather than reduced protein Tyr phosphorylation. Additional studies revealed a significant decrease in sperm hyperactivation as well as in cAMP and PKA substrate phosphorylation levels in sperm from both colonies. The finding that exposure of mutant sperm to dbcAMP and IBMX overcame the sperm functional defects observed in each colony indicated that a commoncAMP-PKA signalling defect led to different phenotypes depending on the genetic background of the animal. These observations indicate that the phenotype of CRISP1 null males is not entirely controlled by the mutation at Crisp1 locus but it is also modulated by the genetic context and reveal the involvement of CRISP1 in the cAMP-PKA signalling cascade associated to sperm capacitation.