IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Participation of CRISP proteins in the fertilization process
Autor/es:
COHEN D.J; MALDERA JA; VASEN G; ERNESTO JI; WEIGEL MUÑOZ M; BATTISTONE A; CUASNICU PS
Lugar:
Sao Paulo
Reunión:
Congreso; Fifth International Conference on Epididymis; 2010
Resumen:
Mammalian fertilization is a complex multi-step
process mediated by different molecules present on both gametes. Rat protein CRISP1, originally
identified in our laboratory, is a member of the evolutionary conserved Cysteine-RIch
Secretory Protein (CRISP) family. CRISP1 is expressed in by the proximal
regions of the epididymis in response to androgens and associates with the
sperm surface during epididymal transit. Evidence indicates the existence of
two populations of CRISP1 on sperm: a major one, loosely bound, released during
capacitation and proposed to act as a decapacitating factor, and a minor one,
strongly associated, that remains on sperm after capacitation and is postulated
to participate in fertilization. Recent results support the participation of a molecular
complex between CRISP1 and zinc in the in
vivo association of the loosely-bound population of CRISP1 with sperm, and
the involvement of membranous vesicles (epididymosomes) in the mechanism by
which CRISP1 strongly associates with sperm.
CRISP1
localizes on the dorsal region of capacitated sperm and on the equatorial
segment of acrosome-reacted cells. Consistent with these localizations, the protein is involved in both
sperm-ZP binding and gamete fusion through its interaction with egg-complementary
sites. The potential roles of CRISP1 in
capacitation and fertilization were further supported by the finding that
capacitated sperm from CRISP1 knock out animals exhibited low levels
of cAMP and protein tyrosine phosphorylation and presented an impaired ability
to fertilize in vitro zona-intact and
zona-free eggs. In spite of this,
CRISP1-deficient mice were fertile, suggesting that testicular CRISP2, also involved in gamete
fusion, and/or other CRISP homologues present on sperm, would compensate for
the lack of CRISP1 in
the mutant mice. Altogether, the presented results support both the participation of CRISP proteins in
different stages of fertilization and the existence of a functional cooperation
between homologue CRISPs as a mechanism to ensure the success of this process.
We
believe these results will contribute to a better understanding of the involvement
of epididymal proteins in gamete interaction as well as to the development of
new and safer fertility regulating methods.
In agreement with our observations in rodents, results
indicate the participation of human epididymal CRISP1 (hCRISP1) in both human sperm-ZP
binding and gamete fusion through its interaction with binding sites in the
human egg. In view of
these results and the finding that immunization of rats with CRISP1 raises
specific antibodies which inhibit animal fertility, immunization studies were carried out in male and
female non-human primates. Results showed that hCRISP1 is immunogenic and that
the produced antibodies enter
the male reproductive tract and recognize the sperm protein without affecting
sperm production or maturation. Altogether, the results obtained increase our
understanding on the molecular mechanisms of gamete interaction and support the
potential use of CRISP family members for the development of new and safer
fertility regulating methods.