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At least 649 records · Page 36Linked to original sources
PubMed2004

GnRH immunocontraception of male cats.

The development of nonsurgical contraceptives for cats may facilitate population control of the species. The purpose of this study was to investigate the utility of GnRH for immunocontraception of male cats. Male cats (n=12) were divided into groups of three and were immunized once with 0 (sham), 50, 200, or 400 microg synthetic GnRH coupled to keyhole limpet hemocyanin and combined with a mycobacterial adjuvant to enhance immunogenicity. GnRH antibody titer, serum testosterone concentration, and scrotal size were determined monthly. At 6 months, semen was collected by electroejaculation and testes were examined histologically. GnRH antibodies were detected in all cats receiving GnRH vaccine by 1 month post-treatment and persisted throughout the study. No dose effect of GnRH was observed; titers were not different among cats treated with 50, 200, or 400 microg GnRH (P=0.5). Six of nine treated cats were classified as responders based on high GnRH antibody titers (>32,000). By 3 months post-treatment, responder cats had undetectable testosterone concentrations and testicular atrophy. Nonresponder cats had GnRH titers of 4000-32,000 and testosterone concentrations intermediate between responder and sham-treated cats. At 6 months, total sperm counts were similar for sham-treated cats (3.1+/-1.8 x 10(6) sperm) and nonresponder cats (3.4+/-1.6 x 10(6) sperm; P=0.7). Only one of the six responder cats produced sperm, none of which were motile. Combined testicular weights of responder cats (1.3+/-0.1 g) were lower than sham-treated controls (5.3+/-1.3 g; P=0.02) and nonresponder cats (2.9+/-0.3 g; P=0.02). Histologic evaluation of the testes revealed that in responder cats, the interstitial cells that were present were pale and shrunken compared to the plump, polyhedral eosinophilic cells in sham-treated cats. GnRH responder cats had marked tubular atrophy with vacuolated Sertoli cells and a paucity of germ cells. Single-dose GnRH treatment resulted in testosterone concentrations and semen quality consistent with immunocastration in a majority of cats treated.

Adjuvants, Immunologic↗
PubMed1981

[Vascular thrombosis in synthetic estrogen-progestogen users: an immune mechanism (author's transl)].

In a number of women the use of combined oral contraceptives (OC) may induce the production of anti-ethinylestradiol antibodies circulating as immune complexes (IC) and which precipitate when the serum is brought at 25% saturation in ammonium sulphate. Testing for tests ICs in 50 women who had never taken OCs, in 100 women on OCs but otherwise healthy, and in 17 women on OCs presenting with vascular thrombosis showed that 20% of all healthy women and more than 95% of women with thrombosis were immunoreactive. The statistically significant correlation found between thrombosis and the presence in the serum of ICs and anti-ethinylestradiol antibodies suggests that an immune mechanism might be responsible for the vascular lesions induced by oral contraceptives containing synthetic estrogens.

Adult↗
PubMed1996

Development of new immunocontraceptives-industrial perspective.

Contraception has been practiced for thousands of years. Nevertheless, it took until the late 1950s and early 1960s before a major breakthrough in contraceptive technology was achieved by the introduction of oral hormonal contraceptives. However, we have not succeeded in the development of non-hormonal contraceptive that is comparable to the pill regarding its efficacy, safety, and acceptance. The immunological interference with the complex fertilization process is a very attractive target in this respect, whereby the zona pellucida, a non-cellular surrounding of all mammalian eggs, represents a potentially ideal target. Another interesting target are sperm: either for the development of a female contraceptive or for a male contraceptive, although the latter approach does not look very promising so far. In conclusion, given the enormous impact on mankind of a growing world population and given the very individual needs for contraceptive methods of different women in one and the same country and in different cultures we should make widely available a whole set of suitable, adjusted methods of fertility control and this includes the search for an effective method of male fertility control.

Contraception, Immunologic↗
PubMed1982

Oral contraceptives and rheumatoid arthritis: further evidence for a preventive effect.

To investigate a reported negative association between the use of oral contraceptives (OC) and the development of rheumatoid arthritis, a case-control study was undertaken to compare the histories of OC use between 228 women with a diagnosis of probable or definite rheumatoid arthritis and 302 women with the diagnosis of soft-tissue rheumatism and/or osteoarthritis. The use of OCs before the onset of joint complaints was acknowledged by 31.1% of the rheumatoid arthritis patients and by 55.6% of the controls. After adjustment for possible confounding variables, the rate ratio for ever use became 0.42 (95% confidence interval 0.27--0.65), while it was 0.40 (0.22-0.72) for ex-users and 0.45 (0.28-0.75) for current users. These findings confirm the finding from the Royal College of General Practitioners Oral Contraceptive Study that the incidence rate of rheumatoid arthritis among OC users was halved.

Adult↗
PubMed1995

Reversible contraception in female baboons immunized with a synthetic epitope of sperm-specific lactate dehydrogenase.

In previous experiments, the sperm-specific isozyme of lactate dehydrogenase (LDH-C) had been purified from mouse testes and shown to suppress the fertility of female baboons by 70% compared to controls. Although these results demonstrated the feasibility of this approach for contraceptive vaccine development, it is not practical to purify enough of the protein from natural sources for human use. Therefore, a need exists to develop a contraceptive vaccine based on synthetic peptides. In the current study, baboon LDH-C cDNA was amplified by the reverse transcriptase-polymerase chain reaction technique. The amino acid sequences of human and baboon LDH-C were 99.3% identical, indicating that the human LDH-C would be an effective antigen in nonhuman primates. The immunodominant epitope of human LDH-C was identified, synthesized, and conjugated to diphtheria toxoid (DT). This construct was used to immunize 15 female baboons; 15 control animals were immunized with DT alone. The fertility of the experimental group was reduced by 75% as compared to the controls (p < 0.02). One year after the last immunization, the contraceptive effect was completely eliminated (no statistical difference between the groups). These results show that a synthetic peptide based on the sequence of human LDH-C is effective in preventing pregnancy in nonhuman primates. The effect is completely reversed 1 yr after the last immunization. The contraceptive effect is not related to serum antibody titers, and human LDH-C is only slightly more effective than mouse LDH-C in female baboons.

Adjuvants, Immunologic↗
PubMedDate not supplied

Immunocontraceptive vaccines for human use.

The development of safe, effective, reversible contraceptive vaccines for the regulation of human fertility would be a significant addition to our contraceptive armamentarium. However, because we are such an out-bred species, immunological responsiveness to any given vaccine is certain to exhibit a high level of inter-individual variation that will impact upon the efficacy, reversibility and feasibility of the approach. Nevertheless a role for vaccines undoubtedly exists as an aid to birth spacing, particularly in developing countries, and as a non-surgical means of inducing sterility in men. Currently vaccines are being researched that target one of two strategic points in the reproductive process, fertilization and the maternal recognition of pregnancy. Our ability to engineer vaccines that target fertilization is hampered by deficiencies in our knowledge of the molecular mechanisms that regulate this process. However, anti-hCG vaccines have advanced to the stage of clinical trials and appear promising.

Animals↗
PubMed1992

Hyperhomocyst(e)inemia, anti-estrogen antibodies and other risk factors for thrombosis in women on oral contraceptives.

Hyperhomocyst(e)inemia was shown to be associated with vascular occlusion in atherosclerotic patients. We have conducted a study to determine if hyperhomocyst(e)inemia was also related to the vascular events observed in women on oral contraceptives, presumably having little or no atherosclerosis. Two hundred women receiving oral contraceptives were included in the study: 100 were healthy controls and 100 had documented vascular occlusion. Determination of serum homocyst(e)ine and anti-estrogen antibody levels wore performed under blind conditions. They were evaluated in logistic regression models in which age and smoking were also included. Women with vascular occlusion had higher levels of homocyst(e)ine (P less than 0.001) and of anti-estrogen antibodies (P less than 0.001) when compared to controls. They were also older (P less than 0.001) and more frequently smokers (P less than 0.05). The above mentioned variables were, in isolation, independent predictors of vascular occlusion. Moreover, a model assessing those variables and their interactions indicated that the levels of anti-estrogen antibodies and smoking increased the predictability in older women, as well as the levels of age-adjusted homocyst(e)ine. The study suggests that the above factors can identify women at risk and that determination of anti-estrogen antibodies and homocyst(e)ine levels may help to detect women predisposed to vascular occlusions when taking oral contraceptives.

Adult↗
PubMed1985

[Immunogenicity of synthetic sex hormones and thrombogenesis].

The ingestion of synthetic steroidal and non-steroidal estrogens may induce antiestrogen antibodies in women on oral contraceptives, and in prostatic patients treated with diethylstilbestrol (DES). Natural sex hormones have no such effect. A radioimmunoassay with tritiated ethinylestradiol or DES was applied to study the prevalence of synthetic sex hormone antibodies in 2 populations: 100 women on estroprogestative hormones and 93 cases of DES treated prostatic cancers. Homologous non-treated controls were compared. Results allowed to identify among treated and asymptomatic subjects an immunoreactive population of 30% women and 47% men. Furthermore, the antibodies were found with a much higher frequency (p less than 0.001) in patients who had experienced a thromboembolic disease while on treatment: 90% of women and 74% of men. The importance of these antibodies as a risk factor, their possible role in promoting vascular lesions, the interest of their detection for the prevention of the vascular risk induced by synthetic sex hormones, are considered.

Adolescent↗
PubMed1976

Oral contraceptive, pulmonary artery thrombosis and anti-ethinyl-oestradiol monoclonal IgG.

Pulmonary artery thrombosis and an anti-ethinyl-oestradiol monoclonal IgGlambda were found to be associated in a 36-year-old woman (Mrs MAI.) who took an oral contraceptive containing 50 mug ethinyl-oestradiol and 500 mug nor-ethisterone daily. After appropriate purification including methods by which the IgG was separated of bound circulating hormones, its binding activity was demonstrated by several methods: passive haemagglutination of oestradiol-benzoate sensitized red blood cells; gel filtration on Sephadex G-25; ultracentrifugation and equilibrium dialysis. IgGlambda MAI bound ethinyl oestradiol (Ka=2-7 X 10(1) M-1) and also 17-beta-oestradiol, with a lower affinity (Ka=0-4 X 10(7) M-1). The valency for these two hormones was near 2. Ethinyl-oestradiol bound to the IgG was displaced by ethinyl-oestradiol itself and in decreasing order of potency by 17-beta-oestradiol, progesterone, oestriol, and testosterone. Oestrone and hydrocortisone had no effect. Although the localization of the binding sites of this IgGlambda was not studied, it is likely that they were the antibody sites of the molecule and, according to immunochemical criteria, it may be classified as a monoclonal anti-ethinyl-oestradiol antibody. It is felt that its association with the pulmonary thrombosis and the oral contraceptive may be significant. This supports the hypothesis of an immunological mechanism for the unexplained thrombotic risk of oral contraceptives.

Adult↗
PubMed1999

At the crossroad of conception and infection: initiatives for immunoglobulin-based contraceptive R & D.

Better understanding of the immunological mechanisms implying the insemination and the infertility of some men and women is needed and crucial to the development of an effective immunocontraceptive method. To provide good protection against conception or infection, and avoid any possible and unexpected complications which immunocontraceptive "vaccine" may arise of, it seems the right time for scientists to create a virtually new thinking for this extremely urgent and important issue. This conceptual article describes our original thoughts of the future development of immunocontraceptives, preferably, based on immunoglobulins rather than vaccines, against human sperm specific antigens and seminal plasma immunosuppressive factors. Its general correctness, advantages and feasibility for fertility regulation and prevention of infection are discussed.

Anti-Infective Agents↗
PubMed2002

Analysis of a human sperm CD52 glycoform in primates: identification of an animal model for immunocontraceptive vaccine development.

Sperm agglutination antigen-1 (SAGA-1) is a human male reproductive tract glycoform of CD52. Unique modification of CD52 N-linked oligosaccharide chains in the epididymis and vas deferens results in the appearance of a carbohydrate epitope that is localized over the entire surface of human spermatozoa. SAGA-1 was characterized by the sperm-inhibitory murine monoclonal antibody (mAb) S19, and it is the target antigen of a human mAb (H6-3C4) associated with antibody-mediated infertility. Collectively, sperm surface localization, antibody inhibition of sperm function, and potential reproductive-tissue specificity identify SAGA-1 as an attractive candidate contraceptive immunogen. To establish an animal model for the study of SAGA-1 in immunologic infertility and immunocontraceptive development, we investigated the appearance of the S19 carbohydrate epitope in nonhuman primates. The S19 mAb demonstrated little to no immunoreactivity by Western blot analysis with protein extracts of spermatozoa from the baboon, marmoset, bonnet, cynomolgus, and pigtailed macaques. Immunohistochemical analysis identified CD52 in the bonnet monkey epididymis; however, the N-linked carbohydrate moiety recognized by the S19 mAb, and unique to SAGA-1, was absent. In contrast, the S19 carbohydrate epitope was identified in chimpanzee sperm extracts by Western blot analysis and in chimpanzee epididymal tissue sections by immunohistochemical analysis, indicating that it is conserved in this close relative of the human. Chimpanzee testis, seminal vesicle, and prostate do not express the S19 epitope. Although anti-CD52 immunoreactivity was identified in the spleen, the carbohydrate moiety recognized by the S19 mAb was absent, corroborating data in the human that demonstrated tissue-specific glycosylation of sperm CD52. Immunofluorescent analysis indicated that the chimpanzee homologue of sperm CD52 was present over the entire spermatozoon. In addition, the S19 mAb agglutinated chimpanzee spermatozoa in a manner similar to the effect observed on human spermatozoa. These data indicate that the distinctive carbohydrate moiety of human sperm CD52 is present in the chimpanzee, and they identify the chimpanzee as the most appropriate primate model to study the potential of this unique CD52 glycoform as a contraceptive immunogen.

Animals↗
PubMed1977

Ultrasound as a new method of male contraception.

Twenty male cats were treated once or twice with 1 watt/sq cm of ultrasound for 10 minutes. Each of 24 male dogs received one to three treatments with 1 watt/sq cm for 10 minutes. Another six dogs were treated with 2 watts/sq cm for 15 minutes. Four Cebus apella monkeys were treated with the same dosage as that used for the cats and dogs. A dosage of 1 watt/sq cm for 10 minutes was also applied to four human patients without the use of anesthetics, and no pain or side effects were noted. In all treated animals as well as in human patients the results indicate that ultrasound significantly suppresses spermatogenesis according to the dosage and frequency of treatment, without any effect on Leydig cells or blood testosterone levels.

Animals↗