Sv. Prasad et al., MOLECULAR-BIOLOGY APPROACHES TO EVALUATE SPECIES VARIATION IN IMMUNOGENICITY AND ANTIGENICITY OF ZONA-PELLUCIDA PROTEINS, Journal of Reproduction and Fertility, 1996, pp. 143-149
Immunocontraception using the glycoproteins of the mammalian zona pell
ucida (ZP) has held great promise because antibodies specific to ZP an
tigens would inhibit fertility and not be abortive. It has been shown,
however, that some ZP proteins will elicit adverse effects since immu
nization may affect ovarian follicular development. These effects vary
among different mammalian species as well as on the source of the ZP
immunogen. Therefore, the use of molecular biology has been essential
in identifying specific ZP protein(s) that inhibit fertility without a
ltering ovarian follicular development and in defining the relationshi
ps of ZP proteins among different species. Use of recombinant ZP prote
ins has allowed us to begin to dissect antigenic domains of ZP protein
s and to evaluate their potential roles in the fertilization process.
Recent studies using recombinant rabbit ZP proteins to immunize cynomo
lgus monkeys (Maraca fascicularis) have shown that the 55 kDa ZP prote
in will elicit antibodies that inhibit sperm binding while not alterin
g ovarian function, in contrast to immunization with a recombinant tru
ncated protein of the 75 kDa ZP protein which causes ovarian dysgenesi
s. The rabbit 55 kDa protein is the homologue of the pig ZP3 alpha spe
rm receptor and the human ZPB protein but is distinct from the mouse Z
P3 sperm receptor. Expression of this protein using the baculovirus ex
pression system has further shown that the 55 kDa protein binds to cap
acitated rabbit spermatozoa over the acrosomal region and induces the
acrosome reaction. Antibodies against this recombinant form of the ZP
also inhibit rabbit spermatozoa from binding to rabbit egg in vitro. T
hese studies demonstrate the need to determine the structure and funct
ion of ZP proteins of different mammalian species to evaluate their po
tential for contraceptive vaccines.