Barber,
M.R. and R.A. Fayrer-Hosken (2000). Evaluation of somatic and reproductive immunotoxic effects of the porcine zona
pellucida vaccination. The Journal of
Experimental Zoology 286(6): 641-646.
ISSN: 0022-104X.
NAL Call Number: 410 J825
Abstract: Immunological, immunocytochemical
and fertility analyses were performed to determine the potential toxic side
effects of porcine zona pellucida
(pZP) vaccinations on target animals, including
horses and dogs. The study was designed to determine the effect of antibodies,
raised against highly purified pZP, on somatic
tissues. Immunocytochemical studies performed with
fixed tissues showed that rabbit anti-pZP antiserum
did not crossreact with brain, heart, lung, kidney,
liver, bladder, stomach, small intestine, large intestine, muscle, skin,
spleen, pancreas, or lymph node of either the dog or horse. To determine the
effect or oral intake on nontarget animals, female
rabbits were fed a contraceptive vaccine containing pZP
glycoproteins and the synthetic trehalose
dicorynomycolate in drakeol
(S-TDCM) adjuvant. Enzyme-linked immunoadsorbent
assay (LISA) analyses showed that rabbits fed with the adjuvanted
pZP proteins did not develop circulating anti-pZP IgG antibodies that crossreacted with pZP.
Furthermore, fertility studies performed on rabbits fed with adjuvanted pZP revealed no
significant differences in the number of embryos or stage of the embryos
produced between the treated and control animals. Results of these studies
suggest that the pZP vaccine delivered to dogs or
horses in field studies have no recognizable somatic tissue effects. Moreover,
there were no side effects on nontarget animals
should they eat the vaccine. This substantiates field trials results about the
safety of the pZP immunocontraceptive
vaccine.
Descriptors: antibody formation, immunologic
contraception, dogs, egg proteins, enzyme-linked immunosorbent
assay, horses, immunoenzyme techniques, immunoglobulin G analysis, membrane glycoproteins, rabbits, swine, vaccines, zona pellucida
Barber,
M.R. and R.A. Fayrer-Hosken (2000). Possible mechanisms of
mammalian immunocontraception. Journal of Reproductive Immunology 46(2):
103-124. ISSN: 0165-0378.
NAL Call Number: QR180.J64
Abstract: Ecological and conservation programs in
ecosystems around the world have experienced varied success in population
management. One of the greatest problems is that human expansion has led to the
shrinking of wildlife habitat and, as a result, the overpopulation of many
different species has occurred. The pressures exerted by the
increased number of animals has caused environmental damage. The humane
and practical control of these populations has solicited the scientific
community to arrive at a safe, effective, and cost-efficient means of
population control. Immunocontraception using zona pellucida antigens,
specifically porcine zona pellucida
(pZP), has become one of the most promising
population control tools in the world today, with notable successes in horses
and elephants. A conundrum has risen where pZP, a
single vaccine, successfully induces an immunocontraceptive
effect in multiple species of mammals. This review describes the most current
data pertaining to the mammalian zona pellucida and immunocontraception,
and from these studies, we suggest several potential mechanisms of immunocontraception.
Descriptors: immunologic contraception, egg proteins,
female, glycosylation, human, lectins,
male, membrane glycoproteins, oligosaccharides,
ovarian diseases, sperm-ovum interactions, adverse effects of vaccinations, zona pellucida
Barber,
M.R., S.M. Lee, W.L. Steffens, M. Ard,
and R.A. Fayrer-Hosken (2001). Immunolocalization of zona pellucida antigens in the
ovarian follicle of dogs, cats, horses and elephants. Theriogenology 55(8): 1705-1717. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Abstract: A comparative evaluation of the location of immunoreactive porcine zona pellucida (pZP) glycoproteins was performed with polyclonal rabbit anti-pZP antibodies on ovarian sections of the dog, cat, horse,
and elephant. For this, formalin (light microscopy) and glutaraldehyde
(transmission electron microscopy [TEM]) fixed ovarian sections were incubated
with antibodies raised against highly purified pZP. Staining patterns were determined with diaminobenzidine (DAB) at the light level. The dog ZP had a
distinct staining distribution that is characterized by intense staining around
the periphery of the ZP and the oolemma and less
dense staining throughout the width of the ZP. In dog follicles that contained
multiple oocytes, there were oocytes
of identical and dissimilar stages. Cat ovarian sections showed uniform
staining of the ZP. Horse results showed uniform staining of ZP and ooplasm, and granulosa cells
(GC). Elephant sections showed staining of the ZP with dense staining at the oolemma, as well as staining of the ooplasm.
In all species the staining of the ZP was not evident until GC differentiation.
In all cases there was no staining of ovarian tissue with control normal rabbit
serum. Specific staining patterns of ZP were evaluated by TEM and immunogold staining. The immunogold-linked
anti-pZP antibodies stained the ZP matrix in all
species. There was staining of ooplasm organelles
suggesting that ZP secretion originates from the oocyte
of the dog and cat. In addition, follicular and ZP measurements were taken that
allowed accurate characterization of follicle stage. These findings suggest
that in all four species the ZP is recognized by anti-pZP
antibodies and there is also evidence to suggest the possible origins of ZP glycoproteins.
Descriptors: cats, immunologic contraception, dogs,
elephants, horses, immunoglobulin g, electron microscopy, ovary, species
specificity, zona pellucida
Courchamp, F. and S.J. Cornell (2000). Virus-vectored immunocontraception
to control feral cats on islands: a mathematical model. The Journal of
Applied Ecology 37(6): 903-913.
ISSN: 0021-8901.
NAL Call Number: 410 J828
Descriptors: cats, wild animals, vertebrate pests, pest
control, biological control, population control, integrated control,
contraception, baits, vectors, viruses, genetic engineering, mathematical
models, islands, genetically modified viral vectors
Dunbar, B.S., G. Kaul, M.
Prasad, and S.M. Skinner (2002). Molecular
approaches for the evaluation of immune responses to zona
pellucida (ZP) and development of second-generation
ZP vaccines. Reproduction Supplement 60: 9-18. ISSN: 1477-0415.
NAL Call Number: QP251.J75 Suppl.
Abstract: It has long been established that there are
major variations in both the immunogenicity and antigenicity of native zona pellucida (ZP) proteins. These differences appear to be
more pronounced with respect to genetically engineered ZP proteins, which do
not have native post-translational modifications (for example glycosylation and sulphation). As
the number of animal species that are now included in population management programmes using native porcine zona
pellucida (PZP) proteins expands, it is increasingly
important to carry out studies to evaluate the immune response variations among
different species as well as the individual variation within a species. In an
attempt to compare these complex immune responses, we have evaluated antibodies
from numerous species immunized with native, genetically engineered ZP and
synthetic ZP peptides. Such an immunocontraceptive
method could have great potential. These studies are critical not only for the
development of predictable immune responses that result in permanent
sterilization versus reversible contraceptive effects, but also for predicting
which vaccinogens (native ZP protein versus
genetically engineered ZP proteins) might have detrimental effects on animal
and human populations.
Descriptors: vaccinogens,
immunologic contraception, egg proteins, zona pellucida, dogs, membrane glycoproteins,
contraceptive vaccines, population control
Fayrer-Hosken, R.A., H.D. Dookwah,
and C.I. Brandon (2000). Immunocontrol in dogs. Animal Reproduction Science 60-61:
365-373. ISSN: 0378-4320.
NAL Call Number: QP251.A5
Abstract: Population control in dogs and cats is an
important goal for many groups. Control measures over the
years has included surgery, hormonal therapy and more recently
immunological control. The current presentation discusses dog population
control with an emphasis on immunologic control. Specifically, vaccination with
purified zona pellucida
(ZP) glycoproteins leads initially to immunocontraception and then to the profound and
irreversible changes of immunosterilization. The
preliminary studies are extremely encouraging on developing a vaccine for
lasting canine population control.
Descriptors: dogs, egg proteins, membrane glycoproteins, population control, methods of
sterilization, vaccination
Ferro, V.A., M.A.H. Khan, V.S. Latimer, D. Brown,
H.F. Urbanski, and W.H. Stimson
(2001). Immunoneutralisation of GnRH-I, without cross-reactivity to GnRH-Ii,
in the development of a highly specific anti-fertility vaccine for clinical and
veterinary use. Journal of Reproductive Immunology 51(2):
109-129. ISSN: 0165-0378.
NAL Call Number: QR180.J64
Descriptors: anti-fertility vaccine, neutralisation,
GnRH, active immunization, rats, luteinizing
hormone, immunocastration, toxicity
Fraser, H.M., A. Gunn, R. Borthwick,
and A.F. Fraser (1975). Letter:
Sterilising by immunisation.
The Veterinary Record 96(14): 323.
ISSN: 0042-4900.
NAL Call Number: 41.8 V641
Descriptors: dogs, female, gonadorelin,
immunization, male, methods of sterilization
Fromme, B., P. Eftekhari,
M. Van Regenmortel, J. Hoebeke,
A. Katz, and R. Millar (2003). A
novel retro-inverso gonadotropin-releasing
hormone (GnRH) immunogen
elicits antibodies that neutralize the activity of native GnRH.
Endocrinology 144(7): 3262-3269.
ISSN: 0013-7227.
NAL Call Number: 448.8 EN2
Descriptors: dependent cancers, vaccines, fertility,
receptor, peptides, cells
Gonzalez, A., A.F. Allen, K. Post, R.J. Mapletoft, and B.D. Murphy (1989). Immunological approaches to contraception in dogs.
Journal of Reproduction and Fertility Supplement 39: 189-198. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: The demand for safe, effective and
cost-efficient means of pet population control has generated interest in the
development of alternatives to surgical gonadectomy.
The purpose of this review is to discuss the potential of immunological
approaches to fertility control and to outline recent developments that may aid
their design. Among the most promising candidates for immunoneutralization
is gonadotrophin releasing hormone (GnRH). We have developed a reliable and reproducible GnRH-protein conjugate antigen and demonstrated that immunologically induced infertility is possible in dogs.
Descriptors: immunologic adjuvants,
antibody formation, contraception, dogs, pituitary hormone releasing hormones, zona pellucida
Gorman, S.P., J.K. Levy, A.L. Hampton, W.R. Collante, A.L. Harris, and R.G. Brown (2002). Evaluation of a porcine zona pellucida vaccine for the immunocontraception of domestic kittens (Felis catus).
Theriogenology
58(1): 135-149. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Abstract: With a seasonally polyestrus
breeding structure, the unwanted domestic cat population has proven difficult
to control. Various lethal methods have been used in an attempt to lower this population
of cats. Recently, humane attempts to control "pest species," such as
the feral cat, have focused on immunocontraception. SpayVac is a vaccine that uses antibodies raised against
porcine (ZP) antigens to prevent fertilization of the ovum. SpayVac,
delivered in a single dose, has been evaluated in fallow deer and several
species of seals with greater than or equal to 90% reduction in fertility and
no adverse reactions. This study evaluated the effectiveness of SpayVac in reducing fertility in domestic kittens. Thirty
female kittens were treated with SpayVac containing
either Freund's complete adjuvant (FCA) or alum, or with a control vehicle.
Kittens were monitored for side effects, estrus cycling at maturity, and
fecundity. Anti-porcine ZP antibodies were quantified by ELISA. Immunohistochemical assays measured the species specificity
of the antibodies produced and IgG binding in vivo.
Despite high anti-porcine ZP antibody titers, neither formulation of SpayVac prevented estrus cycling at maturity or reduced
fecundity. Immunohistochemical assays indicated that
antibodies produced by cats treated with SpayVac
recognized porcine ZP, but not feline ZP.
Descriptors: cats, contraception, antibody formation,
pigs, zona pellucida,
vaccine development, vaccination, adjuvants, elisa, immunohistochemistry,
ovaries
Gupta, S.K., N. Srivastava,
C.K. Govind, N. Sivapurapu,
and G.K. Gahlay (2000). Comparative molecular biology and immunobiology of zona pellucida glycoproteins:
fundamentals and applied aspects for contraception. Proceedings of the
Descriptors: acrosome reaction,
fertilization, immunocontraceptive vaccine, sperm-oocyte binding
Ivanova, M., M. Petrov,
D. Klissourska, and M. Mollova
(1995). Contraceptive
potential of porcine zona pellucida
in cats. Theriogenology 43(5):
969-981. ISSN: 0093-691X.
NAL Call Number: QP251.A1T5
Abstract: The contraceptive potential of solubilized porcine zona pellucida (spZP) was studied in 2
groups of cats after active immunization using slightly different protocols.
Cats from Group 1 (n = 3) were immunized with a total of 300 8g spZP divided in 4 sc multisite
injections (each of 37.5 8g) given at 10 day intervals followed by a booster
150 days after the initial immunization. Cats from Group 2 (n = 5) were
immunized with a total of 400 8g spZP divided in 4 im injections (each of 50 8g) given at 2 wk intervals
followed by a booster 92 days after initial immunization. Immunogen
was emulsified in Complete Freund Adjuvant for the first dose and in Incomplete
Freund Adjuvant for the following 3 doses. The respective controls were
immunized in the same manner using only adjuvant and PBS.
Descriptors: cats, contraceptives, zona
pellucida, pigs, immunization, antibody formation,
binding proteins, immunofluorescence, oocytes, spermatozoa
Jewgenow, K., M. Rohleder,
and
Abstract: Despite many efforts, the control of
reproduction in feral cat populations is still a problem in urban regions
around the world. Immunocontraception is a promising
approach; thus the present study examined the suitability of the widely used
pig zona pellucida proteins
(pZP) for contraception in feral domestic cats.
Purified zona pellucida
proteins obtained from pig and cat ovaries were used to produce highly specific
antisera in rabbits. Antibodies against pZP raised in rabbits or lions
were not effective inhibitors of either in vitro sperm binding (cat spermatozoa
to cat oocytes) or in vitro fertilization in cats,
whereas antibodies against feline zona pellucida proteins (fZP) raised
in rabbits showed a dose-dependent inhibition of in vitro fertilization. Immunoelectrophoresis, ELISA and immunohistology
of ovaries confirmed these results, showing crossreactivity
of anti-fZP sera to fZP and
to a lesser extent to pZP, but no interaction of
anti-pZP sera with fZP. It
is concluded that cat and pig zonae pellucidae express a very small number of shared antigenic
determinants, making the use of pZP vaccine in cats
questionable. A contraceptive vaccine based on feline zona
pellucida determinants will be a better choice for
the control of reproduction in feral cats if immunogenity
can be achieved.
Descriptors: cats, contraception, egg proteins, cross
reactions, enzyme linked immunosorbent assay methods,
fertilization in vitro, immunohistochemistry, lions,
rabbits, sperm-ovum interactions, immunology
Jewgenow, K. and M. Rudolph (2001). Timing and location of zona pellucida synthesis during oogenesis in domestic cats--an ultrastructural
immunohistological investigation. Journal
of Reproduction and Fertility 57(Suppl.):
23-29. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: The application of zona
pellucida proteins for contraception of wildlife and
feral animals, including stray cats, has been promoted since it was
demonstrated to be effective for free-roaming feral mares. Active immunization
with zona pellucida
proteins leads to either reversible or irreversible infertility. Therefore,
knowledge of the timing and location of zona pellucida synthesis during oogenesis
in cats is a key aspect of designing an immunocontraceptive
for felids. Domestic cat ovaries obtained after ovariohysterectomy
were used to produce a specific rabbit antibody against feline zonae pellucidae. Ultrathin sections (70 nm) of cat ovaries were treated with
the anti-zona antibody followed by incubation with
gold-labelled anti-rabbit IgG
for ultrastructural investigation. The gold label was
related to the ultrastructure of oocytes
and granulosa cells. Cat follicles at different
stages of development were examined. The antibody reacted very specifically
with zona pellucida
proteins in fully grown oocytes with a compact zona pellucida. In secondary
follicles, gold labels were found on the zona pellucida and inside granulosa
cells in the vicinity of oocytes. Primary follicles
were labelled inside their cubic granulosa
cells and on fragments of zona pellucida
in the cleft between granulosa cells and the oocyte. Some primordial follicles were characterized by labelling of the granulosa cells.
In conclusion, these results indicate that cat zona pellucida is produced exclusively by granulosa
cells and not by oocytes. Synthesis of zona pellucida takes place at
every stage of follicular development.
Descriptors: antibodies, cats, egg proteins, granulosa cells, immunoglobulin g, immunohistochemistry,
electron microscopy, oogenesis, rabbits, zona pellucida
Ladd, A., G. Prabhu, Y.Y. Tsong, T. Probst, W. Chung, and
R.B. Thau (1988). Active immunization against gonadotropin-releasing
hormone combined with androgen supplementation is a promising antifertility vaccine for males. American Journal of
Reproductive Immunology and Microbiology 17(4): 121-127. ISSN: 8755-8920.
NAL Call Number: QR180.A53
Abstract: Male rats and rabbits were immunized against gonadotropin-releasing hormone (GnRH)
conjugated to tetanus toxoid (GnRH10-TT) using only
materials approved for humans. Testosterone (T)-releasing implants or the
long-lasting T ester testosterone-17-trans-4-n-butyl-cyclohexane carboxylate (TE) was used as supplemental androgen for maintaining
libido. Immunization against GnRH10-TT effectively suppressed fertility
(spermatogenesis) in rats and rabbits. Neither T nor TE administration restored
fertility. Both androgens were effective in maintaining normal libido in rats.
TE, which is not hydrolyzed in rabbits, was less effective in maintaining
normal ejaculatory behavior in this species. Active immunization against GnRH could be a convenient and cost-effective method of
fertility control in males.
Descriptors: androgens, antibody formation, epididymis, fertility, follicle stimulating hormone, gonadorelin, luteinizing hormone,
male, organ weight, prostate, rabbits, rats, seminal vesicles
Ladd, A., Y.Y. Tsong, A.M. Walfield, and R. Thau (1994). Development of an antifertility vaccine for pets based on active immunization
against luteinizing hormone-releasing hormone.
Biology of Reproduction 51(6): 1076-1083. ISSN: 0006-3363.
NAL Call Number: QL876.B5
Abstract: Male dogs and cats were immunized against
LHRH in order to evaluate the feasibility of an immunological approach to pet
contraception. In the first study, dogs were immunized with 100, 500, or 2500
micrograms of LHRH conjugated to tetanus toxoid. A
significant decline in serum testosterone (T) levels was observed in all
immunized dogs, reaching castration levels in some animals by Week 4 and
remaining suppressed in all the immunized dogs through the course of the study.
Testicular histology suggested arrest of spermatogenesis (infertility). The
effects of "immunological castration" were reversible (study 2): steroidogenesis suppressed by "immunological
castration" was restored as antibody titers declined. Effective antibodies
were rapidly reinduced in dogs by a single injection
of LHRH1-TT. In contrast, the level of antibodies induced in male cats (study
3) was not sufficient for "immunological castration." The conclusion
was that active immunization against LHRH could provide a cost-effective, nonsurgical, reversible means to control the fertility of
companion animals.
Descriptors: pets, antifertility
vaccine, immunologic contraception, gonadorelin,
immunization against LHRH, reversible contraception
NAL Call Number: 410 J825
Abstract: In a study designed to evaluate the
contraceptive potential of anti-egg zona pellucida immunization, bitches were injected with isolated
and solubilized zonae pellucidae of either the pig or the dog in saline and
Freund's adjuvant or with saline and adjuvant alone (controls). They were
boosted monthly, and serum samples were collected before the first injection
and 10 days after each injection. The titers of anti-zona
pellucida antibodies in each serum sample were
measured by treating fresh canine oocytes with the
serum, then evaluating antibody binding as indicated by indirect immunofluorescence, precipitation of the zona surface, and penetrability of the zonae
by spermatozoa in vitro. The bitches were bred when they came into estrus. All
three bitches immunized with porcine zonae developed
high titers (1:10,000 or more by indirect immunofluorescence)
of antibodies that cross-reacted with canine zonae to
cause precipitation of the zona surface both in vivo
and in vitro and that completely inhibited penetration of the zonae by spermatozoa in vitro. The two bitches immunized
with canine zonae developed only low titers, and
their sera had little or no effect on treated zonae.
The two control bitches did not develop anti-zona
antibody. None of the bitches immunized against porcine zonae
became pregnant when bred, but one bitch immunized against canine zonae and one control did become pregnant. The bitches
immunized with porcine zonae had somewhat abnormal
cycles for unknown reasons. Thus, we could not establish with certainty whether
the infertility resulted from specific interference with fertilization, as in
vitro, or from alterations in ovarian function, or both.
Descriptors: antibodies, cattle, comparative study, dogs,
estrus, female, fertility, immunization, oocytes,
ovum, zona pellucida
NAL Call Number: QL876.B5
Abstract: To determine the changes in patterns of 17
beta-estradiol and progesterone levels underlying
abnormal cycles in bitches immunized with solubilized
crude porcine zonae pellucidae
(cPZP), to attempt to circumvent these problems by
immunizing with a purified zona fraction (pPZP), and to test the effectiveness of different adjuvants, bitches were immunized with cPZP
or pPZP 2-6 times with no adjuvant, Freund's
adjuvant, alum adjuvant, or the adjuvant CP-20,961. The bitch immunized without
adjuvant had a low titer with a normal cycle and fertility. Immunization with cPZP and adjuvant produced moderate to high titers of antizona antibodies and infertility. Bitches with high
titers experienced abnormal estrous cycles. Estradiol
rose during proestrus, but instead of falling sharply
in early estrus as in controls, it remained elevated. Progesterone did not
rise. The moderate-titered bitches had normal cycles
and steroid patterns. Bitches immunized with pPZP had
moderate titers. Cycles were normal after 3 injections, but after 6 injections
one bitch had an abnormal cycle. One pPZP-immunized
bitch remained fertile but the others were infertile. Alum was the mildest
adjuvant, causing no injection site lesions, but the highest titers occurred
with Freund's and CP-20,961 adjuvants. All three adjuvants induced titers sufficient to inhibit fertility.
Infertility in bitches immunized with PZP may be due to prevention of zona penetration, because their antisera
inhibited zona penetration of oocytes
by spermatozoa in vitro. However, alterations in ovarian function preventing
ovulation and luteinization could be involved in
high-titered bitches.
Descriptors: immunologic adjuvants,
antibodies, contraception, diamines, dogs, estradiol, blood, estrus, fertility, Freund's adjuvant,
immunization, ovum, progesterone, zona pellucida
NAL Call Number: QR180.A53
Abstract: The ovarian histopathology of bitches
immunized with crude (cPZP) or partially purified (pPZP) porcine zona pellucida proteins was examined in order to determine the
cause of abnormal estrous cycles. The majority of immunized bitches had ovarian
cytes. Those immunized with cPZP
had follicular cysts lined with a thin layer of granulosa
cells, while in those immunized with pPZP, the cysts
were lined by a basement membrane with a clump of luteinized
cells. In two bitches immunized with cPZP, oocytes were present only in primordial follicles. Similar
abnormalities were not found in a bitch immunized with human serum albumin or
in 12 untreated bitches. Oocytes flushed from the
oviducts of mated, immunized bitches were degenerating, which may have been a
primary cause of infertility in such bitches. Ovaries studied
2-6 weeks after immunization showed no loss of gap junctional
communication between oocytes and granulosa
cells, nor was any inflammatory reaction seen. IgG
was bound to the zona as revealed by fluoresceinated protein A staining of frozen sections of
those ovaries. Abnormal estrous cycles in PZP-immunized bitches appear to
result from follicular dysgenesis or cyst formation, but
the etiology of these conditions is unresolved.
Descriptors: immunologic contraception, dogs, estrus,
fertilization, immunization, ovary, ovulation, swine, uterus, zona pellucida
Mircu, C., H. Cernescu,
G.H. Ghize, G.H. Bonca, V. Ardelean, and V. Igna (2001). The influence of immunization
with porcine zona pellucida
upon bitch ovaries. Acta Veterinaria 51(4): 235-244. ISSN: 0567-8315.
NAL Call Number: 41.8 V6447
Descriptors: immunocontraception,
veterinary medicine, dogs, zona pellucida,
meiotic competence, ovarian structure
Pineda, M.H. and L.C. Faulkner (1974). Immunologic control of
reproduction in dogs. Canine Practice 1(2): 11. ISSN: 0094-4904.
NAL Call Number: SF991.A1C3
Descriptors: laboratory animals, antibodies, chorionic gonadotropin,
immunologic contraception, endocrine system, gonadotropins,
luteinizing hormone
Saxena,
B.B., A. Clavio, M. Singh, P. Rathnam,
E.Y. Bukharovich, T.J. Reimers
Jr, A. Saxena, and S.
Perkins (2003). Effect of immunization with bovine luteinizing hormone receptor on ovarian function in cats.
American Journal of Veterinary Research 64(3): 292-298. ISSN: 0002-9645.
NAL Call Number: 41.8 Am3A
Abstract: OBJECTIVE: To determine the effect of
immunization with bovine luteinizing hormone receptor
(LH-R) on ovarian function of cats. ANIMALS: 9 adult female domestic cats.
PROCEDURE: 7 cats were immunized with 0.5 mg of LH-R encapsulated in a silastic subdermal implant (3 x
10 mm); 2 served as control cats. Receptors had 80% specific binding to
125I-human chorionic gonadotropin
with a binding capacity of 2,682 pM/mg. Cats received
booster injections of LH-R. Cats were induced to ovulate with luteinizing hormone (LH) releasing hormone on day 345.
Samples of venous blood and vaginal cells were collected through day 395.
Observation of estrus behavior continued until day 516. Serum concentrations of
estradiol, progesterone, thyroid gland hormones, LH,
and LH-R antibody were determined. RESULTS: LH-R antibody was detected in the
sera of immunized cats within 21 days after implantation. Detection of LH-R
antibody was associated with suppression of serum progesterone to < or = 0.5
ng/mL during the study period, compared with
concentrations of 5 to 10 ng/mL in control cats.
Immunized cats did not display signs of estrus. Release of LH after
administration of LH-releasing hormone indicated an intact
hypothalamic-pituitary axis but poor corpus luteum
function. Serum estradiol concentrations remained between 30 to 40 pg/mL in
immunized and control cats. With the decrease antibody titers, hormone
concentrations returned to a pattern consistent with that during fertility.
CONCLUSIONS AND CLINICAL RELEVANCE: Active immunization with LH-R suppressed
corpus luteum function in cats. The effect was
reversible. An LH-R-based antifertility vaccine may
have clinical application in other vertebrates.
Descriptors: cats, drug implants, estradiol,
immunization, LH-R, physiology of ovulation, females
Saxena,
B.B., A. Clavio, M. Singh, P. Rathnam,
Y. Bukharovich, T. Reimers
Jr., A. Saxena, and S. Perkins (2002). Modulation
of ovarian function in female dogs immunized with bovine luteinizing
hormone receptor. Reproduction in Domestic Animals 37(1): 9-17. ISSN: 0936-6768.
NAL Call Number: SF105.A1Z3
Abstract: Adult female dogs were immunized with 0.5 mg
bovine luteinizing hormone receptor (LH-R)
encapsulated in a silastic subdermal
implant and subsequently with four intramuscular booster injections of 0.1 mg
LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks
post-implant. The appearance of LH-R antibody was associated with a decline in
the serum progesterone concentrations to a range of 0-0.5 ng/ml
until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation
and corpus luteum function in immunized dogs. The
immunized dogs did not show signs of 'standing heat' and failed to ovulate when
induced by LH-RH challenge. Serum oestradiol levels,
however, remained in the range of 30-40 pg/ml in both the immunized and the
control dogs. With the decline in the antibody titres,
the hormonal profile and vaginal cytology returned to a fertile state and the
dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs
immunized with LH-R did not show any serious metabolic, local or systemic
adverse effects. The hypothalamic--pituitary gonadal
axis remained intact as indicated by little difference in pituitary LH levels
between control and immunized animals, and by the release of LH by LH-RH
challenge. These studies demonstrate that active immunization of female dogs
with LH-R could immunomodulate ovarian function to
cause a reversible state of infertility. It may be postulated that, due to
extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other
vertebrates.
Descriptors: immunologic adjuvants,
antibodies, corpus luteum, dogs, drug implants, estradiol, gonadorelin,
immunization, luteinizing hormone, ovary,
progesterone, LH receptors
Shigeta, M., A. Hasegawa, Y. Hamada, and
K. Koyama (2000). Analysis of B cell epitopes of a
glycoprotein porcine zona pellucida
(pZP1). Journal of Reproductive Immunology 47(2):
159-168. ISSN: 0165-0378.
NAL Call Number: QR180.J64
Abstract: The zona pellucida (ZP) of mammalian oocytes
forms an extracellular matrix composed of three major
glycoproteins and plays an important role in sperm-zona interactions. As ZP had a strong organ-specific but
species-cross-reactive antigenicity and passive or
active immunization with ZP antigens could impair fertilization, the
possibility of developing a immunocontraceptive
vaccine has been extensively studied. Studies on active immunization with
porcine ZP (pZP) that contain B cell epitopes and T cell epitopes
demonstrated that a temporary infertility could be induced along with the
elevation of antibody titers, but it was always associated with ovarian
failure. This could be due to the oophoritis by
activation of pathogenic T cell immunity. It is the general consideration that
any adverse effects by vaccination should be avoided for an immunocontraception.
From this point of view, the analysis of B cell epitopes
of pZP protein would be helpful for construction of a
safe immunocontraceptive vaccine with zona antigens. We determined the amino acid sequence of the
B epitope in the pZP1 protein by using a monoclonal
antibody (MAb-5H4) that possesses a fertilization blocking ability. In
addition, antiserum raised to the epitope sequence
was revealed to block in vitro fertilization of homologous animal species.
Descriptors: amino acid sequence, monoclonal antibodies, B
lymphocytes, molecular cloning, immunologic contraception, zona
pellucida, membrane glycoproteins
Shivers,
NAL Call Number: SF601.A5
Descriptors: immune regulation of fertility, immunocontraception, dogs, prevention of pregnancy, porcine
zona pellucida
Skinner, S., S. Prasad, T. Ndolo,
and B. Dunbar (1996). Zona pellucida
antigens: targets for contraceptive vaccines. American Journal of
Reproductive Immunology 35(3): 163-174.
ISSN: 8755-8920.
NAL Call Number: QR180.A53
Descriptors: zona pellucida antigens, contraceptive vaccines, mammals,
ovaries, follicular development
Srivastava, N., R. Santhanam, P. Sheela,
S. Mukund, S.S. Thakral,
B.S. Malik, and S.K. Gupta (2002). Evaluation
of the immunocontraceptive potential of Escherichia coli-expressed recombinant
dog ZP2 and ZP3 in a homologous animal model. Reproduction
123(6): 847-887. ISSN: 1470-1626.
NAL Call Number: QP251.J75
Abstract: Dog zona pellucida glycoprotein 2 (dZP2), excluding the N-terminal
signal sequence and the C-terminal transmembrane-like
domain, was cloned and expressed as a polyhistidine
fusion protein in Escherichia coli to
evaluate the immunocontraceptive efficacy of ZP glycoproteins. The recombinant dZP2 (rec-dZP2) revealed a
70 kDa band corresponding to the full length
transcript, as well as several low molecular mass fragments in western blot
analysis. In addition to rec-dZP2, E.
coli expressed recombinant dog ZP glycoprotein 3 (rec-dZP3), which has also
been evaluated for its efficacy to block fertility in a homologous system.
Three groups of female dogs (n = 4 per group) were immunized with rec-dZP2
conjugated to diphtheria toxoid (rec-dZP2-DT),
rec-dZP3 conjugated to DT (rec-dZP3-DT) and DT alone. Immunization of female
dogs with rec-dZP2-DT and rec-dZP3-DT led to generation of antibodies against
the respective ZP proteins as well as to DT. Subsequent to mating, the four
female dogs immunized with rec-dZP2-DT all conceived, which is indicative of
failure of the anti-rec-dZP2 antibodies to block fertility. In the group of
dogs immunized with rec-dZP3-DT, three of four animals did not conceive when
mated with males of proven fertility. The block in fertility was associated
with anti-dZP3 antibody titres. Ovarian
histopathology revealed that the block in fertility in the group immunized with
rec-dZP3-DT is probably manifested by inhibition in the development of
follicles and is due to atretic changes in the zona pellucida. These results,
although preliminary, indicate that immunization with dZP3 may be a feasible
proposition to control dog populations provided that adequate antibody titres are achieved.
Descriptors: immunologic contraception, dog population
control, zona pellucida,
dZP2, Escherichia coli, membrane glycoproteins
Talwar, G.P. and R.K. Naz
(1981). Immunological
control of male fertility. Archives of Andrology
7(2): 177-185. ISSN: 0148-5016.
NAL Call Number: QP253.A54
Abstract: A notable feature of the male gametes is the
presence in them of proteins that are "foreign" to the immune system
of both male and the female. It is there that are considered responsible for
the elicitation of auto- and iso-antibodies in
certain natural infertility cases. By virtue of their dual application in both
sexes the sperm antigens have interesting potential for exploration as possible
agents for control of fertility.
Descriptors: fertility control, immunologic contraception,
BCG vaccine, dogs, male, oligospermia, drug effects
on sperm motility, sperm antigens
Thompson, D.L.Jr. (2000). Immunization
against GnRH in male species (comparative aspects).
Animal Reproduction Science 60/61: 459-469. ISSN: 0378-4320.
NAL Call Number: QP251.A5
Descriptors: GnRH, immunization,
livestock, animal behavior, fertility, neutralization, odors, testes, male
animals, reproduction, aggressive behavior, immunocastration
Verdier, Y., N. Rouet,
G. Farr, and F. Bou (2001). Identification of antigenic fox spermatozoa
surface proteins for use in a contraceptive vaccine. Journal of Andrology (Supplement): 158. ISSN: 0196-3635.
Descriptors: immunocontraception,
contraception method, immunologic method, contraceptive vaccine development,
fertility control
Verhage,
H.G., A.T. Fazleabas, P.A. Mavrogianis,
M.B. O'Day-Bowman, A. Schmidt, E.B. Arias, and R.C.
Jaffe (1997). Characteristics of an oviductal
glycoprotein and its potential role in fertility control. Journal of
Reproduction and Fertility Supplement 51: 217-226. ISSN: 0449-3087.
NAL Call Number: 442.8 J8222 Suppl.
Abstract: At the time of ovulation the lining epithelium
of the mammalian oviduct consists of columnar ciliated and secretory
cells. These mature cells are dependent on ovarian steroids in carnivores. Oestradiol induces differentiation of these cells and
maintains their mature functional state, and progesterone induces
dedifferentiation. The secretory cells synthesize and
secrete an oestrogen-dependent high molecular weight
glycoprotein. The cDNAs encoding oviductal
glycoproteins from several species have been
sequenced and show high similarity. The human cDNA
hybridized with a single message on northern blots of total oviduct RNA
obtained from oestradiol-treated cats (about 2.3 kb)
and dogs (about 2.1 kb). This glycoprotein is the major nonserum
protein present in the oviductal lumen at the time of
ovulation, fertilization and early embryonic development. The glycoproteins associate with the zona
pellucida of oviductal eggs
in all species studied to date. Recent studies suggest that the bovine
glycoprotein facilitates sperm capacitation and
significantly increases the ability of bovine spermatozoa to fertilize bovine oocytes in vitro, that the hamster glycoprotein increases
the sperm penetration rate of the zona pellucida by three times and that the human glycoprotein
increases sperm binding to the zona pellucida by three times. All of the evidence for a
biological function for this glycoprotein is derived from studies performed in
several different species at reproductive stages before fertilization. The
biological actions of this glycoprotein suggest a potential role for the
glycoprotein in fertility control. Specifically, purified or recombinant
glycoprotein may improve success in IVF procedures by enhancing binding of
spermatozoa to the zona pellucida
and improving fertilization rates. The glycoprotein may also be a potential immunocontraceptive target since antibodies generated
against the oviductal glycoprotein may prevent
fertilization by preventing binding of spermatozoa to the zona
pellucida.
Descriptors: fertility, glycoproteins,
animals, species specificity, sperm-ovum interaction, zona
pellucida, immunocontraception
Wango, E.O. and S. Gombe
(1995). The
effect of immunising dogs against an androgen binding
cauda epididymal antigen (caba). Discovery and Innovation 7(3):
265-281. ISSN: 1015-079X.
Descriptors: ammonium sulfate precipitation, antibody,
fertility control, immunocontraceptive vaccine,
protein, testosterone, domestic and wild animals, epididymal
proteins
Zhu, X. and R.K. Naz
(1999). Comparison of ZP3
protein sequences among vertebrate species: to obtain a consensus sequence for immunocontraception. Frontiers in Bioscience: A
Journal and Virtual Library 4: D212-D215.
ISSN: 1093-4715.
Abstract: The deduced ZP3 amino acid (aa) sequences of 13 vertebrate species namely mouse,
hamster, rabbit, pig, porcine, cow, dog, cat, human, bonnet, marmoset, carp,
and frog were compared using the PILEUP and PRETTY alignment programs (GCG,
Wisconsin, USA). The published aa
sequences obtained from 13 vertebrate species indicated the overall
evolutionarily conservation in the N-terminus, central region, and C-terminus
of the ZP3 polypeptide. More variations of ZP3 polypeptide sequences were seen
in the alignments of carp and frog from the 11 mammalian species making the
leader sequence more prominent. The canonical furin proteolytic processing signal at the C-terminus was found
in all the ZP3 polypeptide sequences except of carp and frog. In the central
region, the ZP3 deduced aa
sequences of all the 13 vertebrate species aligned well, and six relatively
conserved sequences were found. There are 11 conserved cysteine
residues in the central region across all species including carp and frog,
indicating that these residues have longer evolutionary history. The ZP3 aa sequence similarities were
examined using the GAP program (GCG). The highest aa similarities are observed between the members of
the same order within the class mammalia, and also
(95.4%) between pig (ungulata) and rabbit (lagomorpha). The deduced ZP3 aa sequences per se may not be enough to build a phylogenetic tree.
Descriptors: amino acid sequence, Callithrix,
cats, cattle, consensus sequence, dogs, egg proteins, fishes, hamsters, human, Macaca radiata,
membrane glycoproteins, mice, rabbits, cell surface
receptors, swine, Xenopus, zona
pellucida