Role of tyrosine phosphorylation in sperm capacitation / acrosome reaction

Capacitation is an important physiological pre-requisite before the sperm cell can acrosome react and fertilize the oocyte. Recent reports from several laboratories have amply documented that the protein phosphorylation especially at tyrosine residues is one of the most important events that occur during capacitation. In this article, we have reviewed the data from our and other laboratories, and have constructed a heuristic model for the mechanisms and molecules involved in capacitation/acrosome reaction

Reduction of fertility in female rabbits and mice actively immunized with a germ cell antigen (GA-1) from the rabbit

Female rabbits and mice were actively immunized against germ cell antigen (GA-1) of 63 kDa molecular mass isolated from rabbit sperm and testis. There was a significant (P P < 0.01) reduction in fertility as seen by mean 7-9 day implants+/-S.D. per mated mouse actively immunized with GA-1 whether through the intraperitoneal route (GA-1, 1.2+/-1.6; controls, 8.0+/-3.4) or through the subcutaneous/intramuscular route (GA-1, 3.8+/-3.4; controls, 10.1+/-3.9). The antisera from these actively immunized animals were negative for sperm agglutinating and immobilizing antibodies. In the Western blot enzyme-immunobinding procedure, the antisera showed specific binding to a single protein of 63 kDa. The incidence of fertilization of eggs recovered from rabbits inseminated with anti-GA-1 antibodies-treated sperm was not significantly different from control rabbits. The percentage of fertilized eggs obtained from rabbits inseminated with anti-GA-1 antibodies-treated sperm that reached the blastocyst stage upon in vitro incubation, however, was significantly less than that for embryos obtained from rabbits inseminated with control serum-treated sperm. Incubation of normal fertilized eggs in vitro with the antibodies did not affect development. Neither antiserum nor immune uterine fluid reacted with 4-day blastocysts in the indirect immunofluorescence technique. It is concluded that active immunization with GA-1 results in post-fertilization reduction of fertility in rabbits and mice by inhibiting early embryonic development.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25986/1/0000052.pd

Development of contraceptive vaccines for humans using antigens derived from gametes (spermatozoa and zona pellucida) and hormones (human chorionic gonadotrophin): current status

Contraceptive research has entered a new phase of development with the advent of hybridoma and DNA recombinant technologies. During the past 5 years, significant advances have been made in this area and now it seems that realistic prospects exist for the development of contraceptive vaccines for use in humans and animals (veterinary, wild and domestic), applicable to both the female and male sexes. Contraceptive vaccines will be valuable supplements to the presently available methods of family planning, and, due to high specificity, the occurrence of limited side-effects if any, low cost and infrequent administration, contraceptive vaccines may have greater acceptability than the currently available methods. Mammalian reproduction starts with the unison of gametes contributed by the male and female partners. Both spermatozoon and oocyte have antigens on the cell surface that are unique, tissue-specific, immunogenic and accessible to antibodies, and binding of the antibodies to these antigens can cause inhibition of gamete function, resulting in a failure of fertilization. Fertilization is followed by embryogenesis, with the early embryo producing several proteins, some of which, eg. human chorionic gonadotrophin (HCG), have a vital role in the establishment and maintenance of early pregnancy. Again, these proteins are accessible to antibodies, and their immunoneutralization can cause anti-fertility effects with loss of early embryo. Thus, the antigens derived from proteins on spermatozoa, oocyte and early embryo, especially HCG, constitute interesting molecules for the development of contraceptive vaccines. The aim of the present article is to review the current status of development of contraceptive vaccines based on antigens derived from sperm cell, oocyte zona pelluci-da and HCG, and to discuss their relative merits and future development

Recent advances in contraceptive vaccine development: a mini-review

Contraceptive vaccines (CV) may provide viable and valuable alternatives to the presently available methods of contraception. The molecules that are being explored for CV development either target gamete production [luteinizing hormone-releasing hormone (LHRH)/GnRH, FSH], gamete function [sperm antigens and oocyte zona pellucida (ZP)], and gamete outcome (HCG). CV targeting gamete production have shown varied degrees of efficacy; however, they either affect sex steroids causing impotency and/or show only a partial rather than a complete effect in inhibiting gametogenesis. However, vaccines based on LHRH/GnRH are being developed by several pharmaceutical companies as substitutes for castration of domestic pets, farm and wild animals, and for therapeutic anticancer purposes such as in prostatic hypertrophy and carcinoma. These vaccines may also find applications in clinical situations that require the inhibition of increased secretions of sex steroids, such as in uterine fibroids, polycystic ovary syndrome, endometriosis and precocious puberty. CV targeting molecules involved in gamete function such as sperm antigens and ZP proteins are exciting choices. Sperm constitute the most promising and exciting target for CV. Several sperm-specific antigens have been delineated in several laboratories and are being actively explored for CV development. Studies are focused on delineating appropriate sperm-specific epitopes, and increasing the immunogenicity (specifically in the local genital tract) and efficacy on the vaccines. Anti-sperm antibody (ASA)-mediated immunoinfertility provides a naturally occurring model to indicate how a vaccine might work in humans. Vaccines based on ZP proteins are quite efficacious in producing contraceptive effects, but may induce oophoritis, affecting sex steroids. They are being successfully tested to control feral populations of dogs, deer, horses and elephants, and populations of several species of zoo animals. The current research for human applicability is focused on delineating infertility-related epitopes (B-cell epitopes) from oophoritis-inducing epitopes (T-cell epitopes). Vaccines targeting gamete outcome primarily focus on the HCG molecule. The HCG vaccine is the first vaccine to undergo Phase I and II clinical trials in humans. Both efficacy and lack of immunopathology have been reasonably well demonstrated for this vaccine. At the present time, studies are focused on increasing the immunogenicity and efficacy of the birth control vaccine, and examining its clinical applications in various HCG-producing cancers. The present article will focus on the current status of the anti-sperm, anti-ZP, anti-LHRH/GnRH and anti-HCG vaccines