Immunized Ewes Research Articles

Immunization against androstenedione to improve the reproductive efficiency in Nilagiri and Sandyno ewes

Healthy Nilagiri (90) and Sandyno (90) ewes were selected and allotted to 3 treatment groups of 15 ewes each, viz. AF (Androstenedione immunogen full dose), AH (Androstenedione immunogen half dose) and CC (Control ewes). The experiment was carried out in main and off breeding seasons. The ewes from AF and AH groups were injected with 2 ml (full dose) and 1 ml (half dose) of androstenedione immunogen at 8 and 4 weeks respectively before the start of breeding season. Immunization of ewes against androstenedione had no significant effect on tupping and lambing percentage. The litter size at birth was significantly increased in AF (1.47±0.07) and in AH (1.40±0.07) groups. The litter size was highest in AF Sandyno ewes (1.60±0.09) and in AH Nilagiri ewes (1.43±0.11). The litter size for immunized group ewes was higher during main breeding season (1.40±0.04) than off breeding season (1.23±0.06). Nilagiri (1.31±0.05) and Sandyno (1.33±0.05) ewes had similar litter size at birth. The litter weight at birth and weaning were significantly higher in AF (3.95±0.13 and 13.89±0.61 kg) groups followed by AH (3.80±0.13 and 13.19±0.61 kg) and CC (3.18±0.13 and 10.89±0.66 kg) groups. The weaning percentage/ survivability were similar for all the treatment groups.

Vaccination with Neospora caninum-cyclophilin and -profilin confers partial protection against experimental neosporosis-induced abortion in sheep

The purpose of this study was to evaluate the protective efficacy of a vaccine consisting of recombinant Neospora caninum-cyclophilin (NcCyP) and -profilin (NcPro) in sheep. At 42 d and 21 d prior to mating, adult Dorset ewes were immunized with the rNcCyP-rNcPro vaccine (Group 1) or co-purifying non-recombinant (NR) control vaccine (Group 2). At 90 days post-mating, all immunized ewes and were challenged by intravenous injection with 106Nesopora caninum Illinois tachyzoites (NcTZ). Significant protection (P < 0.05) was observed in Group 1 with 9 out of 13 ewes giving birth to live-born lambs (69.2%), whereas all Group 2 ewes aborted (6/6). Neospora caninum was detected by PCR in both fetal and placental tissues from all Group 2 aborting ewes and in the placental tissues of Group 1 aborting ewes. In contrast, tissues and placentas of Group 1 live-born lambs were Neospora DNA-negative. Immunoreactive Neospora antigens were demonstrated in placentas associated with abortions, but not in tissues of aborted fetuses or those of the live-born lambs and their associated placentas. Anti-NcCyP and anti-NcPro titers were high in sera from Group 1 ewes and were further boosted by challenge infection, resulting in long-lasting (≥14.5 mos.) elevated titers. Lambs born to Group 1 ewes also had high NcCyP and NcPro titers in pre-colostrum sera. Immunofluorescence staining (IFA) of NcTZ with Group 1 post-immunization sera revealed both surface and internal TZ staining, a pattern consistent with that observed with rabbit sera to rNcCyP or rNcPro. Infection of NR-vaccinated ewes produced high but transient anti-NcCyP and anti-NcPro Ab titers. The results indicate that the NcCyP-NcPro vaccine elicited strong anti-N. caninum responses and conferred significant protection against abortion and transplacental transmission of N. caninum TZ in sheep.

Prevalence of Eimeria Species in Sheep with A Special Reference to Vaccinated Pregnant Ewes for Maternal Immunity for the First Time

Sheep coccidiosis is an infection of economic and medical importance and have been observed in almost all alive sheep rearing in the world. Examination of 928 sheep fecal samples from different localities in Kaloubia Governorate for detection of Eimeria infection revealed a prevalence rate of 72.5% (n= 673/928). The identified Eimeria species oocysts were Eimeria candelas (78.3%), E. granulosa (63%), E. ovinoidalis (41%), E. parva (31.5%), E. pallida (22.1%), E. intricata (6.8%), E. faurei (6.2%) and E. ahasta (4.9%). The prevalence rate was high in females (76.3%) as compared to males (68.3%). The incidence of infection peaked in winter (83.1%) followed by spring (80.8%), while the lowest rate was in summer (61.0%). High prevalence rate was recorded in ages > 6 months (90.8%), followed by 6-12months (73.6%), while the lowest rate was in sheep over 1 year of age (55.6%). Single infection was recorded in 26.6% of infected sheep. Double infection rate was in 29.7% while mixed infection rate was in 43.7%. With regard to breeds, Rahmany and Osemy breed showed the highest infection rate (80.9% and 73.9%; respectively). On the other hand, Baladi breed showed the lowest infection rate (58.3%). Immunized dam with UV attenuated Eimeria oocysts and their progeny showed a significant increase in both IgG and IgM as compared to non-immunized control group. Biochemical analysis Immunized dams and their progeny showed high level of albumin, Beta and Gamma concentration levels as compared to control dams and their progeny. Conclusion, it could be concluded that Egyptian sheep was infected by 8 species of Eimeria with predominant of Eimeria crandalis and Eimeria granulosa. New born lambs from immunized ewes have high serum immunoglobulin especially IgG compared to those from non-immunized ewes. Recommendation, Immunization of pregnant ewes by two doses UV irradiated Eimeria oocysts one month before parturition to give protection to their progeny.

Efeito da imunização ativa com líquido folicular bovino na prolificidade de ovelhas da raça Ideal e mestiças Suffolk x Ideal

The experiment was carried out in “Posto Experimental de Ovinos e Caprinos do Instituto de Zootecnia de Itapetininga (SP)” to study the effect of active immunization with bovine follicular fluid (bFF) on Ideal and Sufflolk x Ideal ewes prolificity rate reared in subtropical climatic conditions.The experiment was entirely randomized, beirg 2 treatments: controle (n=30) and immunized (n=30) ewes and 2 breeds Ideal and Sufflolk x Ideal. From 30 treated ewes with bFF 29 (96,7%) presented immunological response. Otherwise, immunization have no effect (P&gt;.05) on fertility rate or oestral behavior. Average prolificity rate of immunized ewes (1,3) was higher (p.05) on prolificity rate, but occurried immunization effect (P

The Influence of Active Immunization Against Adrenocorticotropin Hormone on Galactopoiesis in Merino Ewes

Background: Chronic active adrenocorticotropin hormone (ACTH) immunization of ewes (with a previous history of immunization) resulted in elevated titres of antibody against ACTH, which induced a reduction in circulating levels of cortisol. Objectives: The aim of the present study was to investigate: a) the influence of active immunization against ACTH on milk production of the ewe as assessed by milk intake of the lamb measured with two different methods, b) whether the stimulation of levels of β -end and α-MSH in the circulation can result in a similar increase in the expression of these peptides in the milk of the lactating ewe, thereby producing a milk with high analgesic properties. Materials and Methods: Ten primiparous Merino ewes (4-5 years old) during their first 5 weeks of lactation were used in the experiment. Milk intake of each lamb can be used to give the ewe’s milk yield per unit time, and this can be used for secretion of peptides over time. This was determined by two different techniques: the deuterium oxide method and the weigh-suck-weigh method. β -end, α-MSH and cortisol were measured in blood samples and β-end, α-MSH in milk samples using RIAs (Radio Immune Assay). Results: Plasma β-end and α-MSH in ACTH-immune animals increased to 3 and 38-fold respectively, although the level of α-MSH is most likely exaggerated by the presence of α-MSH antibodies in the ACTH immune plasma, as α-MSH comprises the N-terminal 13 amino acids of ACTH. Antibodies also were detected in the plasma of lambs of immune ewes after birth, at levels, which were comparable to those measured in the ewes during the period of colostrum production and thereafter decreased to much lower levels by the end of the experiment. Plasma β-end and α-MSH in the lambs of immune ewes were significantly higher than those measured in the lambs of control ewes. Conclusions: The immunization procedure had no effect on feed intake, live weight gain and milk production of ewes nor was the growth rate or milk intake of the lambs altered. The expression of β-end and α-MSH in milk was also unaffected by the high concentrations of these hormones in the circulation of immune ewes.

Use of exposure history to identify patterns of immunity to pneumonia in bighorn sheep (Ovis canadensis).

Individual host immune responses to infectious agents drive epidemic behavior and are therefore central to understanding and controlling infectious diseases. However, important features of individual immune responses, such as the strength and longevity of immunity, can be challenging to characterize, particularly if they cannot be replicated or controlled in captive environments. Our research on bighorn sheep pneumonia elucidates how individual bighorn sheep respond to infection with pneumonia pathogens by examining the relationship between exposure history and survival in situ. Pneumonia is a poorly understood disease that has impeded the recovery of bighorn sheep (Ovis canadensis) following their widespread extirpation in the 1900s. We analyzed the effects of pneumonia-exposure history on survival of 388 radio-collared adults and 753 ewe-lamb pairs. Results from Cox proportional hazards models suggested that surviving ewes develop protective immunity after exposure, but previous exposure in ewes does not protect their lambs during pneumonia outbreaks. Paradoxically, multiple exposures of ewes to pneumonia were associated with diminished survival of their offspring during pneumonia outbreaks. Although there was support for waning and boosting immunity in ewes, models with consistent immunizing exposure were similarly supported. Translocated animals that had not previously been exposed were more likely to die of pneumonia than residents. These results suggest that pneumonia in bighorn sheep can lead to aging populations of immune adults with limited recruitment. Recovery is unlikely to be enhanced by translocating naïve healthy animals into or near populations infected with pneumonia pathogens.

Inhibin immunization in Norduz sheep

Abstract. The objective of this study was to investigate the possibility of increasing ovulation rate in Norduz sheep by immunization against inhibin-based peptide immunogens. A total of 18 primiparious Norduz ewes were used for this experiment. Eight ewes have received two times inhibin α-subunit 1-32 porcine vaccine with 3 weeks interval. The rest was kept as control. Antibody binding test by standard ELISA method did not provide reliable information. However, ultrasonographic inspection showed that significantly high number of follicle with 5 mm and larger diameter (P&lt;0.01) has developed in immunized ewes. Moreover, 3 of immunized ewes have lambed twin. However, twin birth was not observed in control group.

Evaluation of a British computer model to simulate gastrointestinal nematodes in sheep on Canadian farms

With increasing levels of anthelmintic resistance worldwide and a growing demand to produce more organic products, utilisation of control strategies for gastrointestinal nematodes (GIN) that minimize the use of anthelmintics becomes even more important. This study evaluated the farm-level performance of an existing predictive sheep parasite model from the United Kingdom (UK), using Canadian data. The UK model simulates the epidemiology of three major GIN species of interest ( Teladorsagia spp., Haemonchus spp. and Trichostrongylus spp.) and provides a prediction about seasonal parasite levels of lambs and ewes. Model inputs were generated by using data from the first 2 years of a 3-year study (2006–2008) which examined the epidemiology of GIN parasitism in Ontario sheep flocks. Required input data included ewe parasite egg output, pasture-related information and management dynamics. Farm visits in 2006 and 2007 provided relevant data that were collected monthly during the grazing season, on six and seven occasions respectively. These data were collected from 10 ewes and 10 lambs on each farm. For 23 Ontario farms with available data, only 11 farms in 2006 and 14 in 2007 had suitable data to run in the model because the Canadian study was not specifically designed with this simulation model in mind. Observed values for faecal egg counts (FEC) were compared to the model FEC outputs and assessed using linear regression analysis. There was adequate fit between observed and simulated data for 8 of the 11 farms modelled using data generated in 2006 ( F = 7.55–42.66, df = 10–11, R 2 = 0.43–0.81, p = 0.021 to <0.001) and with 8 of the farms modelled using data generated in 2007 ( F = 5.56–35.82, df = 9–11, R 2 = 0.36–0.82, p = 0.040 to <0.001). We suggest that the poor fit between observed and simulated data for some data sets may be attributable to low-level infection on farms making regression difficult due to insensitivity of the egg count method at low values, or a pattern for immunity in ewes that contradicted the model assumptions. Required model modifications focused on accommodating the differences between UK and Canadian management styles; specifically the practice of bringing lambs indoors for weaning which was sometimes used on Canadian farms.

Pulsed GnRH secretion and the FSH secretory peaks that initiate ovarian antral follicular wave emergence in anestrous ewes

In ewes, immunization against GnRH blocks LH pulses but mean serum FSH concentrations are only partly reduced; the fate of the FSH peaks that precede ovarian follicular waves has not been studied. In this study, we used immunization against GnRH to examine the need for pulsed GnRH secretion in the genesis of FSH peaks in the anestrous ewe. Six anestrous ewes were given a GnRH immunogen on Day 0 and a booster injection on Day 28. Control ewes ( n = 6) received adjuvant only. Transrectal ultrasonography was performed daily for 2 days prior to and 10 days following both the primary (Days −2 to 10) and booster (Days 26–38) injections and for a 13-day period beginning 26 days after booster injection (Days 54–66). Blood samples were collected daily. Intensive bleeding (every 12 min for 7 h) was performed on Days 9, 37, and 65 of the experimental period to characterize the pulsatile pattern of LH secretion. GnRH antibody titers were increased and LH pulses were abolished immediately after booster immunization ( P < 0.05). The number of FSH peaks, FSH peak concentration and amplitude and basal FSH concentrations were only decreased in immunized ewes in the period of observations starting 26 days after booster immunization ( P < 0.05); however, some peaks were still seen. The number of follicular waves was decreased in the period around booster immunization and no follicular waves were seen during the period starting 26 days after booster immunization in immunized ewes ( P < 0.05). In summary, in anestrous ewes, when pulsed LH secretion was abolished by immunization against GnRH, the peaks in serum concentrations of FSH that trigger ovarian follicular waves continued for a period of time. We concluded that although blocking the effects of GnRH gradually causes a diminution of FSH secretion, there is no acute requirement for GnRH in the regulation of FSH peaks. The existence of FSH peaks in the absence of follicular waves, and pulsed LH secretion, suggests that some endogenous rhythm may drive the occurrence of FSH peaks, independent of both changes in negative feedback by secretory products from ovarian antral follicles and GnRH.

Immunisation of ewes against oestradiol-17&amp;#223 in an attempt to increase the yield of viable embryos with superovulation

Immunisation of ewes against oestradiol-17&amp;#223 in an attempt to increase the yield of viable embryos with superovulation

Autoimmunization of ewes against pregnancy-associated glycoproteins does not interfere with the establishment and maintenance of pregnancy

Pregnancy-associated glycoproteins (PAGs) are a large grouping of placental proteins that belong to the aspartic peptidase gene family. Although useful to detect pregnancy in ruminant species, the function of these molecules is unclear. Several PAGs expressed by trophoblast binucleate cells can enter the maternal circulation, suggesting that they could have a systemic role in altering maternal physiology. The objective of this work was to examine whether these circulating placental antigens were important in pregnancy by actively immunizing ewes against them. PAGs were purified by pepstatin-affinity chromatography and conjugated to the immunogenic protein, keyhole limpet hemocyanin (KLH). Ewes were immunized with PAG–KLH conjugate (n = 22) or with KLH alone (n = 9), and bred to intact rams. Blood samples, collected on Day 0 (day of estrus), Day 10, Days 15 to 25 and weekly throughout pregnancy, were analyzed for PAG by an ELISA. On Day 30, pregnancy was confirmed by ultrasound. Ewes immunized against PAG–KLH produced a range of reactive anti-PAG titers, whereas all immunized ewes had high anti-KLH immunoreactivity. PAGs became detectable in the anti-KLH (control) ewes at Day 21.6 ± 2.2 of pregnancy. Those ewes immunized against PAGs (n = 7), that had very low immunoreactivity toward PAGs, had measurable PAG by Day 22.9 ± 1.3, and their PAG serum profiles throughout pregnancy did not differ from the controls. Those exhibiting moderate to high anti-PAG immunoreactivity (n = 15), had significantly lower PAG concentrations than controls, with antigen not becoming detectable until Day 48.1 ± 15.6. The decrease in circulating PAG in the immunized animals did not correlate with changes in pregnancy rates, lamb number or lamb birth weight. These results suggest that while PAGs may play a role in maintaining pregnancy, their major contribution is likely to be at the fetal–maternal interface. Their actions at extra-placental sites are presumably of more secondary importance.

GnRH or eCG treatment fails to restore reproductive function in GnRH immunized ewes

This study was designed to evaluate the potential of using eCG or GnRH in restoring reproductive functions in GnRH immunized ewes. Thirty-three multiparous Kıvırcık ewes were randomly assigned into either control group ( n = 11) or immunization group ( n = 22). Ewes were immunized against GnRH by injecting with a cocktail of ovalbumin-LHRH-7 (ovalbumin-GnRH-7) and thioredoxin-LHRH-7 (thioredoxin-GnRH-7) fusion proteins generated by recombinant DNA technology in April. 500 IU eCG or 0.008 mg GnRH analogue was used to induce ovulations. Serum GnRH antibodies were present in animals of the immunized group beginning the second week after the first immunization and maintained throughout the study (14 months). Immunization caused anestrus in immunized ewes. eCG or GnRH analogue administration given after 14 days progestagen (20 mg fluorogestone acetate, FGA) treatment during breeding season (mid July) did not induce ovulation in these ewes. Two more attempts with single or multiple eCG injections failed to induce ovulation in this group as well. It appears that the gonadotropin stimulation was not of adequate time since neither eCG nor GnRH administration was able to restore reproductive function in immunized animals. The immunization effect lasted more than a year. These results suggest that GnRH immunization exerts its effect via the hypothalamo-pituitary axis and that more than such stimulation is required to overcome the reproductive suppression.

A potential krimpsiekte vaccine

Krimpsiekte, a chronic form of cardiac glycoside poisoning, is an important plant-induced intoxication of small stock in South Africa. It is caused by cumulative, neurotoxic bufadienolides, such as cotyledoside. A cotyledoside-bovine serum albumin conjugate was synthesized to immunize animals. The efficacy of the cotyledoside-conjugate in inducing an immunological response was ascertained in rabbits (n = 4) and sheep (n = 4) by determining cotyledoside antibody titres with an ELISA using cotyledoside-hen ovalbumin as antigen. The formation of anticotyledoside antibodies was induced in both rabbits and sheep following immunization with the cotyledoside-protein conjugate. Protection provided by the vaccine was demonstrated by challenging sheep (n = 4) with repeated, daily doses of cotyledoside (0.015 mg/kg) administered intravenously, commencing 45 days after the initial vaccination. One control animal died on Day 3 of the challenge period and the other was severely affected after administration of the third cotyledoside dose. The immunized ewes (n = 2) remained clinically unaffected and the challenge was suspended following six daily injections. Vaccination as a means of preventing krimpsiekte seems to be quite feasible and deserves further investigation.

The Effects of Immunizing Sheep with Different BMP15 or GDF9 Peptide Sequences on Ovarian Follicular Activity and Ovulation Rate1

The aims of these studies were to determine the abilities of antisera against different regions of ovine bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF9) to inhibit ovarian follicular activity, estrus (mating), and ovulation in sheep. The 9-15-mer peptides were conjugated to keyhole limpet hemocyanin (KLH) and used to generate antibodies against the flexible N-terminal regions of the mature protein as well as against regions in which dimerization of the protein or interaction with a type 1 BMP or a type 2 TGFB or BMP receptor was predicted to occur. Ewes (n = 10 per treatment group) were vaccinated with KLH or the KLH-BMP15 (n = 9 different peptides) or KLH-GDF9 (n = 10) peptides in Freund adjuvant at five consecutive monthly intervals. Overall, antisera generated against peptides that corresponded to amino acid residues 1-15 of the N-terminus of the BMP15 or GDF9 mature protein or GDF9 amino acid residues 21-34 were the most potent at inhibiting ovulation following primary and single booster vaccination. Several other BMP15 (8/9) or GDF9 (6/10) treatment groups, but not KLH alone, also produced significant reductions in the numbers of animals that ovulated, although 2, 3 or 4 booster vaccinations were required. Anovulation was commonly associated with the inhibition of normal ovarian follicular development and anestrus. The in vitro neutralization studies with IgG from the BMP15 or GDF9 immunized ewes showed that the mean inhibition of BMP15 plus GDF9 stimulation of (3)H-thymidine uptake by rat granulosa cells was approximately 70% for animals without corpora lutea (CL), whereas for animals with one to three CL or more than three CL, the inhibition was 24%-33% or 27%-42%, respectively. In summary, these data suggest that reagents that block the biological actions of BMP15 or GDF9 at their N-termini have potential as contraceptives or sterilizing agents.

Meat and Livestock Association Plenary Lecture 2005. Oocyte signalling molecules and their effects on reproduction in ruminants

Sheep (Ovis aries) are a highly diverse species, with more than 900 different breeds that vary significantly in their physiological characteristics, including ovulation rate and fecundity. From examination of inherited patterns of ovulation rate, several breeds have been identified with point mutations in two growth factor genes that are expressed in oocytes. Currently, five different point mutations have been identified in the BMP15 (GDF9b) gene and one in GDF9. Animals heterozygous for the GDF9 and/or the BMP15 mutations have higher ovulation rates than their wild-type counterparts. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile owing to arrested follicular development. In bovine and ovine ovaries, GDF9 was expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 was expressed exclusively in oocytes from the primary stage: no data for the ontogeny of BMP15 expression are currently available for cattle. In vitro, ovine growth differentiation factor 9 (oGDF9) has no effect on (3)H-thymidine incorporation by either bovine or ovine granulosa cells, whereas ovine bone morphogenetic protein 15 (oBMP15) has modest (1.2- to 1.6-fold; P < 0.05) stimulatory effects. Ovine GDF9 or oBMP15 alone inhibited progesterone production by bovine granulosa cells, whereas in ovine cells only oGDF9 was inhibitory. The effects of oGDF9 and oBMP15 together were often cooperative and not always the same as those observed for each factor alone. Active immunisation of ewes with BMP15 and/or GDF9 peptides affected ovarian follicular development and ovulation rate. Depending on the GDF9 and/or BMP15 vaccine formulation, ovulation rate was either increased or suppressed. A primary and single booster immunisation of ewes with a BMP15 peptide in a water-based adjuvant has led to 19-40% increases in lambs born per ewe lambing. Collectively, the evidence suggests that oocyte signalling molecules have profound effects on reproduction in mammals, including rodents, humans and ruminants. Moreover, in vivo manipulation of these oocyte signalling molecules provides new opportunities for the management of the fertility of ruminants.

Immunization protocols against C ryptosporidium parvum in ovines: protection in suckling lambs

Ovine colostrum and milk from immunized ewes were tested for their ability to prevent cryptosporidiosis in the lambs experimentally infected with 10 6 oocysts of Cryptosporidium parvum at 36–48 h of age (day 0 post-infection). All lambs became infected and developed clinical cryptosporidiosis. However, lambs fed by immunized dams have shown shedding involved, significantly, fewer oocysts and lasted for a shorter period than in control lambs. In addition, diarrhoea was less severe. The best results emerged in lambs of ewes immunized by intramuscular injection of an emulsion of 2 ml of Freund's complete adjuvant and 2 ml of C. parvum antigen in sterile phosphate buffered saline solution, administrated four weeks before parturition, together with an intramammary infusion of 25 μg of antigen in 2 ml of sterile PBS emulsified in 2 ml of Freund's incomplete adjuvant, which showed the highest anti- C. parvum titres in lacteal secretions. In their case, the onset of output of oocysts was delayed by two days, the patent period was shortened by three days, their diarrhoea continued for only three days, and the quantity of oocysts shed decreased by 77%. The outcome was that at the end of the study they had a live weight gain of 2 kg more than the lambs in the control group. These results indicate that lactogenic immunoprophylaxis should help mitigate the financial losses caused by cryptosporidiosis in small ruminants, as well as reducing the risk of infection of humans through the decreased contamination of the environment with oocysts.

020. Oocyte signalling molecules and their effects on reproduction in ruminants

Sheep (Ovis aries) are a highly diverse species with more than 900 different breeds that vary significantly in their physiological characteristics including ovulation rate and fecundity. From examination of inherited patterns of ovulation rate in sheep, several breeds have been identified with point mutations in two growth factor genes that are expressed in oocytes. Currently, five different point mutations have been identified in the BMP15 (GDF9b) gene and one in GDF9. Animals heterozygous for the GDF9 and/or the BMP15 mutations have higher ovulation rates (i.e. +0.6 to +5.0) than their wild-type contemporaries. In contrast, those homozygous for any of the aforementioned BMP15 or GDF9 mutations are sterile due to abnormal follicular development from the primary stage of growth. In bovine and ovine ovaries, GDF9 is expressed exclusively in oocytes throughout follicular growth from the primordial stage of development, whereas in sheep BMP15 is expressed exclusively in oocytes from the primary stage: no data for BMP15 are available for the cow. In vitro, ovine GDF9 (oGDF9) has no effect on 3H-thymidine incorporation by either bovine or ovine granulosa cells, whereas oBMP15 has modest (1.2 to 1.6-fold; P &lt; 0.05) stimulatory effects. GDF9 or BMP15 alone inhibited progesterone production by bovine granulosa cells, whereas with ovine cells only GDF9 was inhibitory. The effects of GDF9 and BMP15 together were often cooperative and not always the same as those observed for each factor alone. Active immunisation of ewes with BMP15 and/or GDF9 peptides affected ovarian follicular development and ovulation rate. Depending on the GDF9 and/or BMP15 vaccine formulation, ovulation rate was either increased or suppressed. For example, immunisation of ewes with a BMP15 peptide in a water based adjuvant has led to a 25% increase in lambs born per ewe lambing. Collectively the evidence suggests that oocyte signalling molecules have profound effects on reproduction in mammals including rodents, humans and ruminants. Moreover, that in vivo manipulation of these oocyte signalling molecules provides a new approach to managing the fertility of ruminants.

Physiological effects of major genes affecting ovulation rate in sheep

Genetic mutations with major effects on ovulation rate in sheep were recently identified in two genes of the transforming growth factor (TGFβ) superfamily and a TGFβ receptor, namely bone morphogenetic protein 15 (BMP15), otherwise known as the growth differentiation factor 9b (GDF9b), GDF9 and activin-like kinase 6 (ALK6) otherwise known as the BMP receptor type IB (BMPRIB). Animals homozygous for the BMP15 or GDF9 mutations are anovulatory whereas animals heterozygous for BMP15 or GDF9 or heterozygous or homozygous for ALK6 have higher than normal ovulation rates. Immunisation of ewes against BMP15 or GDF9 shows that both are essential for normal follicular development and control of ovulation rate. Common features of fertile animals with the BMP15, ALK6 (and possibly GDF9) mutations are changes in oocyte development during early preantral follicular growth, earlier maturation of granulosa cells and ovulation of mature follicles at smaller diameters. In summary, these findings have led to a new paradigm in reproductive biology, namely that the oocyte plays a key role in regulating the ovulation rate.

Physiological effects of major genes affecting ovulation rate in sheep

Genetic mutations with major effects on ovulation rate in sheep were recently identified in two genes of the transforming growth factor (TGFβ) superfamily and a TGFβ receptor, namely bone morphogenetic protein 15 (BMP15), otherwise known as the growth differentiation factor 9b (GDF9b), GDF9 and activin-like kinase 6 (ALK6) otherwise known as the BMP receptor type IB (BMPRIB). Animals homozygous for the BMP15 or GDF9 mutations are anovulatory whereas animals heterozygous for BMP15 or GDF9 or heterozygous or homozygous for ALK6 have higher than normal ovulation rates. Immunisation of ewes against BMP15 or GDF9 shows that both are essential for normal follicular development and control of ovulation rate. Common features of fertile animals with the BMP15, ALK6 (and possibly GDF9) mutations are changes in oocyte development during early preantral follicular growth, earlier maturation of granulosa cells and ovulation of mature follicles at smaller diameters. In summary, these findings have led to a new paradigm in reproductive biology, namely that the oocyte plays a key role in regulating the ovulation rate.

Immunization against LHRH in ewes for suppressing reproductive functions and possibilities of using PMSG or LHRH in restoring reproductive functions in LHRH immunized ewes

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