ABSTRACT
Equine uterine development, including endometrial histogenesis, begins prenatally and is completed postnatally. Little is known about this process in the horse. Uterine tissue was acquired from 38 foals, ranging in developmental age from gestational day (GD) 300 to postnatal day (PND) 180, for assessment of endometrial histogenesis. Patterns of endometrial cell proliferation were evaluated by multispectral imaging of uterine tissue sections stained immunofluorescently for Ki-67. Labeling index (LI, % labeled cells) for Ki-67 was calculated for each endometrial cell compartment (luminal epithelium, glandular epithelium, stroma). Histologically, nascent endometrial glands were present in all pre- and postnatal uterine tissues. Overall, Ki-67 LI increased (P < 0.0001) from the pre-to postnatal periods, and was higher (P < 0.0001) in epithelium as compared to stroma. Postnatally, endometrial Ki-67 LI increased (P < 0.0001) from week 1 to week 24. Our findings confirm that, in contrast to neonatal patterns of uterine development described for domestic ungulates, equine endometrial histogenesis begins prenatally, marked by the appearance of uterine glands as early as GD 300. Epithelial proliferation associated with maturation of the equine endometrium is pronounced by postnatal week 24.
Subject(s)
Endometrium , Uterus , Animals , Animals, Newborn , Epithelium , Female , Fetus , HorsesABSTRACT
BACKGROUND: Population control of domestic, wild, invasive, and captive animal species is a global issue of importance to public health, animal welfare and the economy. There is pressing need for effective, safe, and inexpensive contraceptive technologies to address this problem. Contraceptive vaccines, designed to stimulate the immune system in order to block critical reproductive events and suppress fertility, may provide a solution. Filamentous bacteriophages can be used as platforms for development of such vaccines. OBJECTIVE: In this review authors highlight structural and immunogenic properties of filamentous phages, and discuss applications of phage-peptide vaccines for advancement of immunocontraception technology in animals. RESULTS: Phages can be engineered to display fusion (non-phage) peptides as coat proteins. Such modifications can be accomplished via genetic manipulation of phage DNA, or by chemical conjugation of synthetic peptides to phage surface proteins. Phage fusions with antigenic determinants induce humoral as well as cell-mediated immune responses in animals, making them attractive as vaccines. Additional advantages of the phage platform include environmental stability, low cost, and safety for immunized animals and those administering the vaccines. CONCLUSION: Filamentous phages are viable platforms for vaccine development that can be engineered with molecular and organismal specificity. Phage-based vaccines can be produced in abundance at low cost, are environmentally stable, and are immunogenic when administered via multiple routes. These features are essential for a contraceptive vaccine to be operationally practical in animal applications. Adaptability of the phage platform also makes it attractive for design of human immunocontraceptive agents.
Subject(s)
Contraception, Immunologic , Inovirus/metabolism , Vaccines, Contraceptive/immunology , Animals , Genetic Vectors/genetics , Genetic Vectors/metabolism , Inovirus/chemistry , Inovirus/immunology , Peptide Library , Vaccines, Subunit/immunology , Vaccines, Virus-Like Particle/immunologyABSTRACT
The increasing incidence of reproductive anomalies, described as testicular dysgenesis syndrome, is thought to be related to the exposure of the population to chemicals in the environment. Bisphenol A (BPA) and di(2-ethylhexyl)phthalate (DEHP), which have hormonal and antihormonal activity, have attracted public attention due to their presence in consumer products. The present study investigated the effects of BPA and DEHP on reproductive development. Timed-pregnant female rats were exposed to BPA and DEHP by gavage from gestational days 12 to 21. Results showed that prenatal exposures to test chemicals exerted variable effects on steroidogenic factor 1 and GATA binding protein 4 protein expression and increased (P < .05) sex-determining region Y-box 9 and antimüllerian hormone protein in the infantile rat testis compared with levels in the control unexposed animals. Pituitary LHß and FSHß subunit protein expression was increased (P < .05) in BPA- and DEHP-exposed prepubertal male rats but were decreased (P < .05) in adult animals relative to control. Exposure to both BPA and DEHP in utero inhibited (P < .05) global DNA hydroxymethylation in the adult testis in association with altered DNA methyltransferase protein expression. Together the present data suggest that altered developmental programming in the testes associated with chemical exposures are related to the disruption of sexual differentiation events and DNA methylation patterns. The chemical-induced effects impact the development of steroidogenic capacity in the adult testis.
Subject(s)
Benzhydryl Compounds/pharmacology , Diethylhexyl Phthalate/pharmacology , Environmental Pollutants/pharmacology , Estrogens, Non-Steroidal/pharmacology , Phenols/pharmacology , Plasticizers/pharmacology , Sex Differentiation/drug effects , Testis/drug effects , Animals , Anti-Mullerian Hormone/metabolism , DNA Methylation/drug effects , DNA Modification Methylases/drug effects , DNA Modification Methylases/metabolism , Endocrine Disruptors/pharmacology , Female , Follicle Stimulating Hormone, beta Subunit/drug effects , Follicle Stimulating Hormone, beta Subunit/metabolism , GATA4 Transcription Factor/drug effects , GATA4 Transcription Factor/metabolism , Gonadal Dysgenesis , Luteinizing Hormone, beta Subunit/drug effects , Luteinizing Hormone, beta Subunit/metabolism , Male , Pituitary Gland/drug effects , Pituitary Gland/metabolism , Pregnancy , Prenatal Exposure Delayed Effects , Rats , Sex-Determining Region Y Protein/drug effects , Sex-Determining Region Y Protein/metabolism , Steroidogenic Factor 1/drug effects , Steroidogenic Factor 1/metabolism , Testicular Diseases , Testis/metabolismABSTRACT
Prebreeding vaccination should provide fetal and abortive protection against bovine viral diarrhea virus (BVDV) and bovine herpesvirus 1 (BoHV-1) but not impede reproduction when administered to cattle before estrus synchronization and breeding. The objective was to assess reproductive performance when naive beef heifers were vaccinated with modified-live viral (MLV) vaccine 2 days after unsynchronized estrus, and then revaccinated with MLV vaccine at 10 or 31 days before synchronized natural breeding. Sixty beef heifers naive to BVDV and BoHV-1 were randomly assigned to one of four treatment groups. Groups A and B (n = 20 per group) were vaccinated with MLV vaccine containing BVDV and BoHV-1 at 2 days after initial detected estrus, and then revaccinated 30 days later, which corresponded to 10 days (group A) or 31 days (group B) before synchronized natural breeding. Groups C and D (n = 10 per group) served as controls and were vaccinated with an inactivated vaccine that did not contain BVDV or BoHV-1 at the same time points as groups A and B, respectively. Estrous behavior was assessed using radio frequency technology. Estrus synchronization was performed, with initiation occurring at revaccination (groups A and C) or 21 days after revaccination (groups B and D). After synchronization, heifers were submitted to a bull breeding pasture for 45 days. At the end of the breeding period, heifers were assessed for pregnancy using ultrasonography. Progesterone concentrations were evaluated at estrus and 10 days after unsynchronized and synchronized estrus, at initial pregnancy check, and at the end of the study. All pregnant heifers in groups A and B and five pregnant heifers in group C were euthanized between 44 and 62 days of gestation and ovarian and conceptus tissues were assayed for BVDV and BoHV-1. Vaccination with MLV vaccine did not result in significant negative reproductive impact based on the duration of interestrus intervals, proportion of heifers exhibiting estrus within 5 days after synchronization, serum progesterone concentrations, pregnancy rates, and pregnancies in the first 5 days of the breeding season. Bovine viral diarrhea virus and BoHV-1 were not detected in luteal tissue, ovarian tissue, or fetal tissues. Use of MLV vaccine did not impede reproduction, when revaccination was performed at 10 or 31 days before synchronized natural breeding.
Subject(s)
Bovine Virus Diarrhea-Mucosal Disease/prevention & control , Cattle/physiology , Estrus Synchronization , Herpesviridae Infections/veterinary , Pregnancy Rate , Viral Vaccines/immunology , Animals , Cattle/blood , Diarrhea Viruses, Bovine Viral , Dinoprost/administration & dosage , Dinoprost/pharmacology , Estradiol/blood , Female , Gonadotropin-Releasing Hormone/administration & dosage , Gonadotropin-Releasing Hormone/pharmacology , Herpesviridae Infections/prevention & control , Herpesvirus 1, Bovine , Pregnancy , Progesterone/administration & dosage , Progesterone/blood , Progesterone/pharmacologyABSTRACT
Rat astrocyte function is changed by diabetes mellitus relative to the nondiabetic state and we believe that altered function contributes to the central nervous system symptoms manifested by individuals with diabetes. We report here a comparison of astrocyte glutamate uptake and GFAP expression in streptozotocin-induced type 1 diabetic rats and insulin-treated diabetic rats at 4 and 8 weeks following diabetes onset. In glial plasmalemmal vesicle (GPV) preparations from treated rats, insulin prevented the increase observed in untreated, diabetic rats of both sodium-dependent and sodium-independent glutamate uptake. We determined by immunoblotting and immunohistochemistry that insulin treatment prevented the decrease of GFAP expression detected in the cerebral cortex, hippocampus, and cerebellum of untreated, diabetic rats. These observations indicate that insulin effects on astrocyte function are significant in managing diabetes-induced central nervous system pathology.
Subject(s)
Astrocytes/drug effects , Diabetes Mellitus, Experimental/drug therapy , Glial Fibrillary Acidic Protein/metabolism , Glutamic Acid/metabolism , Hypoglycemic Agents/pharmacology , Insulin/pharmacology , Animals , Astrocytes/metabolism , Blotting, Western , Cerebellum/drug effects , Cerebellum/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Diabetes Mellitus, Experimental/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Immunohistochemistry , Male , Rats , Rats, Wistar , Sodium/metabolism , Time FactorsABSTRACT
Mares (n = 37) were treated from 4h after breeding through 2 days post-ovulation with oxytocin or cloprostenol. Oxytocin (20 units i.m.) was administered every 6 h and cloprostenol (250 mcg i.m.) daily. Luteal function was impaired for several days following treatment, however, lower progesterone levels among cloprostenol treated mares in this study did not result in decreased pregnancies. Pregnancy outcome at 15 days post-ovulation was not different between the oxytocin (13/18) and cloprostenol (13/19) treatment groups, respectively (P = 0.80). The results of this study indicate cloprostenol can be used to treat post-breeding mares through the second day following ovulation without decreasing pregnancy outcome.
Subject(s)
Cloprostenol/administration & dosage , Corpus Luteum/drug effects , Horses/physiology , Ovulation , Oxytocin/administration & dosage , Pregnancy Outcome , Animals , Breeding , Corpus Luteum/physiology , Female , Kinetics , Pregnancy , Progesterone/bloodABSTRACT
Mares (n = 30) were treated in the post-ovulatory period with saline, oxytocin, or cloprostenol (Clo). Dose, administration frequency and treatment day (Day 0, 1 or 2 post-ovulation) were evaluated. Interovulatory interval of control cycles was 22.7 (+/-0.36) days with a range of 20.6 (+/-1.44) to 23.8 (+/-1.39) days among all treatment groups. Mares treated with two micro-doses of cloprostenol on Day 2 post-ovulation had the shortest interovulatory interval. This group also had the lowest mean circulating progesterone concentrations on Days 3-7 and 13, and was the slowest group to reach concentrations of 5 ng/ml. Repeated administration of cloprostenol over 24 h in the early post-ovulatory period may more effectively impair luteal function than single doses. This could negatively affect pregnancy outcome but may be effective for lysing the early post-ovulatory luteal structure when mares are not bred.