Prasad S V, Wilkins B, Dunbar B S
Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
J Reprod Fertil Suppl. 1996;50:143-9.
Immunocontraception using the glycoproteins of the mammalian zona pellucida (ZP) has held great promise because antibodies specific to ZP antigens would inhibit fertility and not be abortive. It has been shown, however, that some ZP proteins will elicit adverse effects since immunization 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 altering ovarian follicular development and in defining the relationships of ZP proteins among different species. Use of recombinant ZP proteins has allowed us to begin to dissect antigenic domains of ZP proteins and to evaluate their potential roles in the fertilization process. Recent studies using recombinant rabbit ZP proteins to immunize cynomolgus monkeys (Macaca fascicularis) have shown that the 55 kDa ZP protein will elicit antibodies that inhibit sperm binding while not altering ovarian function, in contrast to immunization with a recombinant truncated protein of the 75 kDa ZP protein which causes ovarian dysgenesis. The rabbit 55 kDa protein is the homologue of the pig ZP3 alpha sperm receptor and the human ZPB protein but is distinct from the mouse ZP3 sperm receptor. Expression of this protein using the baculovirus expression system has further shown that the 55 kDa protein binds to capacitated 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. These studies demonstrate the need to determine the structure and function of ZP proteins of different mammalian species to evaluate their potential for contraceptive vaccines.
使用哺乳动物透明带（ZP）糖蛋白的免疫避孕法前景广阔，因为针对ZP抗原的特异性抗体可抑制生育能力且不会导致流产。然而，研究表明，某些ZP蛋白会引发不良反应，因为免疫接种可能会影响卵泡发育。这些影响在不同哺乳动物物种以及ZP免疫原来源之间存在差异。因此，分子生物学的应用对于确定抑制生育能力而不改变卵泡发育的特定ZP蛋白以及明确不同物种间ZP蛋白的关系至关重要。重组ZP蛋白的使用使我们能够开始剖析ZP蛋白的抗原结构域，并评估它们在受精过程中的潜在作用。最近利用重组兔ZP蛋白免疫食蟹猴（食蟹猕猴）的研究表明，55 kDa的ZP蛋白可引发抑制精子结合的抗体，同时不改变卵巢功能，而用75 kDa ZP蛋白的重组截短蛋白免疫则会导致卵巢发育不全。兔55 kDa蛋白是猪ZP3α精子受体和人ZPB蛋白的同源物，但与小鼠ZP3精子受体不同。使用杆状病毒表达系统表达该蛋白进一步表明，55 kDa蛋白在顶体区域与获能的兔精子结合，并诱导顶体反应。针对这种重组形式ZP的抗体在体外也能抑制兔精子与兔卵的结合。这些研究表明，有必要确定不同哺乳动物物种ZP蛋白的结构和功能，以评估它们作为避孕疫苗的潜力。
