Evaluation of the potential contraceptive use of hCRISP1 in a non-human primate model”

ELLERMAN DA; WEIGEL MUÑOZ M; COHEN DJ; GOLDEWEIC NM; DA ROS VG; YUDIN A; TOLLNER T; OVERSTREET J; CUASNICU PS

Buenos Aires, Argentina

Jornada; Jornada de actualización en Andrología 2009; 2009

Sociedad Argentina de Andrología

  Evidence indicates that human epididymal protein CRISP1 (Cystein Rich Secretory Protein 1) participates in gamete fusion through complementary sites on the surface of the human egg. To evaluate whether hCRISP1, as its rodent counterpart, is relevant for fertility, immunization studies were carried out in a non-human primate model. Male and female cynomolgus macaques (Macaca Fascicularis) were immunized with either recombinant protein hCRISP1 coupled to MBP (Maltose Binding Protein) or MBP alone as control (4 injections, every 25 days). ELISA of sera collected at different intervals after immunization revealed the presence of circulating anti-hCRISP1 antibodies in animals of both sexes, with levels that increased as a function of time. Differently from control and pre-immune groups, sera from hCRISP1-immunized monkeys were able to specifically recognize native CRISP1 in monkey and human sperm protein extracts when evaluated by Western blot. Sperm number, morphology and motility in hCRISP1-immunized animals were not different from controls, suggesting that the presence of anti-hCRISP1 antibodies would not affect sperm production or maturation. Finally, ejaculated sperm from hCRISP1- but not MBP-immunized animals, exhibited labelling in the acrosomal region when subjected to indirect immunofluorescence using only second antibody, indicating the association of the anti-hCRISP1 antibodies with sperm in vivo. In view of previous results showing that immunization of rats with native or recombinant CRISP1 raised a specific immune response that significantly inhibited male and female fertility, our results in primates  support both the involvement of antibodies against hCRISP1 in human immunoinfertility, and the potential use of this epididymal protein for the development of human fertility regulation methods.