Pathophysiology of the periparturient egg rise in sheep: the role of prolactin

The involvement of prolactin in the periparturient rise in the faecal nematode egg count in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to adult immune ewes from three weeks before parturition to three weeks afterwards. Ten ewes were injected twice daily with 2-bromo-alpha-ergocryptine (bromocriptine), an antagonist of prolactin secretion, for two weeks starting two days after lambing while 10 ewes remained untreated. Bromocriptine treatment was initiated approximately two weeks pre partum in three other ewes. Plasma pepsinogen concentrations rose significantly by one week after the start of O circumcincta larval challenge in all the ewes but faecal egg counts remained negative until approximately one week post partum. Plasma prolactin concentration was reduced to a very low level in all bromocriptine treated ewes but this did not alter the dynamics of the periparturient rise in faecal egg counts. Neither cell-mediated nor humoral immunity of the ewes, as assessed by their sensitivity to BCG inoculation and by antibody titre raised against horse red blood cells, respectively, were impaired during the rise in faecal egg count, nor were these parameters altered by manipulation of plasma prolactin concentration. Lamb growth rate was not retarded by low plasma prolactin concentration in the bromocriptine treated ewes. These results are not consistent with the generally held hypothesis that elevated plasma prolactin concentration is directly associated with the periparturient rise.     

Pathophysiology of the periparturient egg rise in sheep: a possible role for IgA.

The relationship between anti-parasite IgA antibody levels in plasma and the periparturient egg rise in sheep was investigated. Ostertagia circumcincta larvae (5000 third stage larvae three times weekly) were administered to three groups of seven adult immune ewes from 12 weeks before until three weeks after lambing (group 1) or from six (group 2) or 14 (group 3) weeks before until three weeks before lambing. Seven additional ewes were not challenged (group 4 controls). Ewes in groups 1, 2 and 4 received anthelmintics 14 weeks before lambing. Challenge of the pregnant ewes with O circumcincta larvae resulted in substantial increases in faecal egg counts only during the periparturient period regardless of the larval dosing regimen. Furthermore, the periparturient rise in faecal egg counts was closely associated with a significant increase in anti-parasite IgA antibody levels in plasma. This rise in IgA antibody levels occurred at a time when IgA is transported from the gut to milk during early lactation. It is postulated that this may lead to a temporary reduction in abomasal antibody levels of ewes and hence permit the establishment of larvae and, or, the emergence and development of inhibited larvae and thereby lead to the periparturient rise in faecal egg count.     

Comparison of ivermectin, oxfendazole and levamisole for use as anthelmintics during the periparturient period in sheep

Ewes synchronised with progestin impregnated sponges to reduce the spread of lambing were treated during the periparturient period with anthelmintic. The suppression of nematode egg output in faeces was measured in ewes given ivermectin either by subcutaneous injection or orally, or oxfendazole or levamisole orally. Ivermectin and oxfendazole reduced the output of eggs in the faeces of the ewes significantly (P less than 0.05) and the period of suppressed egg output was extended when ivermectin was given by subcutaneous injection. Plasma pepsinogen activity was estimated as a measure of abomasal damage. Pepsinogen values were significantly (P less than 0.001) lower in those animals treated with ivermectin by subcutaneous injection than in control animals. Levamisole showed a poorer response in terms of the output of eggs in faeces than either ivermectin or oxfendazole.     

The sequential analysis of local inflammatory cells during abomasal nematode infection in periparturient sheep

A technique to take sequential tissue biopsy samples in multiparous, periparturient ewes from the abomasal mucosa is described, developed in parallel in Scotland and New Zealand. Samples were extracted via abomasal cannulae inserted into the wall of the abomasum and exteriorised through dorso-ventral laparotomy. Animals recovered quickly post-surgery, and tolerated the cannula and sampling without any adverse signs of pain or discomfort. The technique was deployed in two pilot studies to investigate the sequential mucosal inflammatory cell responses in well-defined parasitological models, during the periparturient relaxation of immunity in ewes infected with gastrointestinal nematodes and subjected to different feeding treatments. One experiment (Moredun Research Institute, Scotland) involved the infection of twin-bearing ewes with Teladorsagia circumcincta L3 either before, or after lambing. By feeding ewes with different levels of protein supplementation, preliminary data on the impact of nutrition on the eosinophil, mucosal mast cell and globule leucocyte responses during this period were investigated. A similar study was also performed at Lincoln University, New Zealand, to investigate these cell responses in sheep fed relatively high or low protein diets during pregnancy, and infected with a combined immunisation regime of T. circumcincta and Trichostrongylus colubriformis L3. These studies confirmed the phenomenon termed the periparturient relaxation in immunity (PPRI) where a transitory increase in faecal egg counts is observed during late pregnancy and lactation, and this effect was exacerbated during protein undernutrition. Although the number of animals was low in each experiment and the cell responses variable, the results together suggest a reduction in the number of mucosal mast cells and globule leucocyte during the PPRI when protein supply was restricted. The present paper thus describes a successful technique to monitor ovine mucosal cell populations during local immune responses in normal and pregnant sheep. It is envisaged that this technique will be a powerful adjunct to investigations into mucosal immune mechanisms and disease pathogenesis, and will be employed to confirm the influence of dietary protein on the local inflammatory cell responses during the PPRI.     

Effect of nutritional status and fat reserves on the periparturient immune response to Haemonchus contortus infection in sheep

A study was made of the effect of body fat stored by ewes in early pregnancy on the subsequent immune response to gastrointestinal parasites around parturition. Pregnant ewes were given access to a lucerne pelleted diet either ad libitum (H) or at approximately 0.70 of their maintenance requirements (L) from the 42nd day of pregnancy in order to achieve a clearly differentiated level of body reserves by the 90th day of pregnancy. Then, all animals were put on the same plane of nutrition till 3 weeks after parturition. All ewes in both groups received 7,000 infective larvae of Haemonchus contortus per week for 7 weeks prior to lambing. The dietary treatments led to large differences between both groups of ewes in back-fat thickness that had a high correlation with mean plasma concentrations of leptin. In spite of the fact that animals were on the same plane of nutrition at infection time, host resistance, as measured by faecal egg counts, was significantly affected by the nutritional treatment established during early pregnancy. This effect produced noticeable differences in worm size and in worm burden at lambing. The response was accompanied by a marked increase in circulating eosinophils in better-fed ewes than in those maintained on a restricted diet in early pregnancy. Serum pepsinogen concentration, however, was inversely affected by the nutritional treatment till lambing, showing a maximum difference as early as 2 weeks after infection. The results support the view that higher levels of nutrition during early pregnancy enhance the expression of immunity against gastrointestinal parasites around parturition. Furthermore, the differences in the immune response appeared associated with serum leptin levels suggesting that leptin may be a key link between nutritional status and the protective immune reactivity against GI nematode infection.     

Comparison of the anthelmintic efficacy of oxfendazole or ivermectin administered orally and ivermectin administered subcutaneously to sheep during the periparturient period

The suppression of nematode egg output in faeces was measured in ewes treated just before lambing with either oxfendazole or ivermectin by oral drench or with ivermectin by subcutaneous injection. Ivermectin and oxfendazole given orally were similarly effective, whereas ivermectin given by subcutaneous injection extended the period of suppressed egg output by about one week. The more persistent anthelmintic effect of ivermectin given subcutaneously was probably due to its extended half-life in the plasma of treated sheep. Plasma pepsinogen activity was less in the sheep given anthelmintic than in the untreated controls. Ivermectin caused a significantly greater reduction in pepsinogen activity than oxfendazole and was more effective when given subcutaneously than when given orally.     

Use of a long acting injectable formulation of moxidectin to control the periparturient rise in faecal Teladorsagia circumcincta egg output of ewes

A field study was conducted in a sheep flock in the south east of Scotland with a history of ivermectin resistance in Teladorsagia circumcincta. The objective of the study was to compare the effects of single anthelmintic treatments in ewes before turn-out onto pasture that was contaminated with a moderate level of overwintered, ivermectin resistant, T. circumcincta infective larvae. The ewes were treated according to label directions with either a long acting injectable formulation of moxidectin (1mg/kg; affording up to 14weeks persistent action against macrocyclic lactone (ML)-susceptible T. circumcincta) or an oral formulation of moxidectin (0.2mg/kg; affording up to 5weeks persistent action against ML-susceptible T. circumcincta). The lambs were enrolled in the normal management of the farm, and received a total of three oral ivermectin treatments during the 16week study. The efficacy of both treatment strategies in controlling the periparturient rise in faecal nematode worm egg counts and subsequent pasture contamination was assessed from the faecal worm egg counts of the ewes and their lambs between lambing and weaning. Ewes that were treated with the oral formulation of moxidectin shed approximately 3.5 times more T. circumcincta eggs between lambing and weaning than ewes that were treated with the long acting formulation of moxidectin. This difference was reflected in the faecal worm egg counts of the lambs that were grazed alongside the different treatment groups of ewes. The results of the current study demonstrate persistent efficacy of the long acting formulation of moxidectin against an ivermectin resistant T. circumcincta population. The decreased pasture contamination after treatment could lead to improved lamb growth and a need for fewer anthelmintic treatments, thus potentially reducing one possible selection pressure for anthelmintic resistance. However, treatment with the long acting formulation of moxidectin would give rise to fewer susceptible nematodes being present in refugia, which could increase another possible selection pressure for anthelmintic resistance, depending on the subsequent grazing management of that pasture. The rationale for use of a persistent anthelmintic drug to control the periparturient rise in faecal ML-resistant T. circumcincta egg output of the ewes is discussed and potential differences in selection for macrocyclic lactone anthelmintic resistance using the different formulations of moxidectin are acknowledged.     

Periparturient rise in faecal helminth egg counts of Udah sheep in the Zaria area of Nigeria

The trichostrongylid egg output in the faeces of seven lambing and seven barren Udah ewes was compared during the beginning of the rainy season in 1974. Both groups showed an increase in egg counts which reached a considerably higher level in the lambing ewes. The highest level, a mean count of 2 650 eggs/g, was reached 2 weeks after lambing.It is suggested that the increase was due to helminths, mainly Haemonchus sp., which had been inhibited during the dry season and resumed their development at the beginning of the rainy season.The rapid decline in egg counts recorded 5–6 weeks after lambing was considered to be due to self cure associated with high rainfall.     

The peri-parturient rise in sheep. Faecal worm egg counts in normal and late lambing ewes

The trichostrongylid and strongylid egg output in a group of ewes lambing in March, the middle of the usual lambing time in the Netherlands, was compared with counts in groups of older ewes and yearling ewes lambing in May-June and with counts in a group of barren ewes. The groups lambing in March showed only a rise related to parturition date as normally seen in the Netherlands. A few of the late lambing ewes showed a slight rise in spring, but all of them showed a peri-parturient rise related to parturition date. In the late lambing ewes and in the barren ewes egg counts due to reinfection were seen in summer. It is concluded that under the present circumstances a true spring rise, the calendar phenomenon, occurs very irregularly, while a peri-parturient rise related to the parturition date is a common phenomenon. The occurence of high egg counts in summer, excluding consideration on the barren ewes, in the late lambing ewes only, suggests that changing the traditional husbandry system may influence the epidemiological pattern of the trichostrongylid infections.     

Alterations in bovine lymphocyte function during the periparturient period

Lymphocytes from 8 Holstein heifers were evaluated during the periparturient period for mitogen-induced lymphocyte blastogenic responses. Phytohemagglutinin P- and concanavalin A-induced lymphocyte blastogenesis increased 2 and 3 weeks before parturition, respectively. However, by the first week after parturition, lymphocyte blastogenesis was markedly impaired.     

Alterations in bovine neutrophil function during the periparturient period

Neutrophils from 8 Holstein heifers were evaluated for function during the periparturient period. Random migration, ingestion of bacteria, superoxide anion production, native (nonenhanced) chemiluminescence, iodination, and antibody-dependent, cell-mediated cytotoxicity by neutrophils were determined. Foremilk samples were evaluated for bacteria. Significant (P less than 0.05) increases in random migration of neutrophils, iodination, and chemiluminescence were evident 2 weeks before parturition and then decreased dramatically by the first week after parturition. These impairments of neutrophil function after parturition may be manifested as a severe cumulative deficit in the native defenses afforded by the neutrophil.     

The effect of weather on the occurrence and magnitude of periparturient rise in trichostronglyid nematode egg output in Dorper ewes in a semi-arid area of Kajiado District of Kenya

An investigation was carried out to assess the effects of weather on the occurrence and magnitude of the periparturient rise (PPR) in trichostrongylid nematode egg output in breeding Dorper ewes. The study was conducted over three breeding seasons on a ranch in the semi-arid area of Kajiado District in Kenya between June 1999 and December 2001. During each breeding season 20 ewes randomly selected from the breeding stock and 20 others selected from the unmated yearlings were monitored for faecal strongyle egg counts every 3 weeks. The lambing seasons were timed to coincide with the onset of the short rains (October–November 1999), the mid-short rains (November–December 2000) and the end of the dry season (September–October 2001). In each season higher egg outputs were recorded in the peri-parturient ewes compared to the unmated yearlings. The highest PPR occurred in September 2001, when lambing coincided with the end of the dry season, possibly as a result of maturation of hypobiotic larvae. The lowest PPR occurred in November 2000 when the onset of lambing coincided with the mid-short rains, possibly owing to low pasture infectivity associated with a long dry spell between January and October of the same year. The results of this study indicate that PPR occurred when lambing coincided with both the wet and the dry seasons. However, the magnitude was greatly influenced by the season when lambing occurred. It was also influenced by resumption of development of hypobiotic larvae and the nutritional status of the ewes. Not only should control of gastrointestinal nematode parasites in this area aim at preventing the occurrence of PPR by treating ewes 2–3 weeks before they are to lamb and during lactation, but the anthelmintic used must also eliminate hypobiotic larvae. In addition, the animals must be given supplementary feeding during this period.     

Serum leptin levels during the periparturient period in cows

Serum leptin concentrations were measured in antenatal and postnatal cows housed at two different locations. The mean serum leptin concentration was 9.2 +/- 0.6 ng/m l (n=22) in one group, and was slightly lower in the other (7.4 +/- 0.4 ng/ml, n=54), probably because of the different nutritional conditions between the two groups. There was no consistent variation in relation to the menstrual cycle and the periparturient period in both groups. Moreover, serum leptin concentrations during the periparturient period were independent of the number of delivery and the incidence of mastitis and milk fever. These results are quite different from those in rodents and human, suggesting the different regulatory mechanism of circulating leptin concentration in cows.     

Genetic disorders affecting reproduction and periparturient care

There are numerous genetic diseases influencing reproduction and periparturient care in dogs including such disorders as anasarca, cleft palate, swimmers, congenital heart disease, and the various conditions that cause excessive bleeding. It is probable that all breeds of dogs are at risk for these or other traits that influence whelping and neonatal care. Therefore, genetic counseling should be considered as an important aspect of prenatal and pediatric veterinary medicine.     

Genetics and physiology of leptin in periparturient dairy cows

In dairy cattle, the increase in milk yield has been accompanied by a more negative energy balance (EB) during early lactation and a decrease in fertility. As the hormone leptin is involved in regulation of nutritional status and reproductive function this hormone is an interesting protein to investigate during the periparturient period in dairy cattle. This study was performed to get insight into the function of leptin during the periparturient period and to perform an association study between polymorphisms in the bovine leptin gene and leptin receptor gene and fertility as well as production traits. Leptin concentrations in the periparturient cow undergo remarkable changes; leptin concentrations were high during late pregnancy and declined to a nadir at parturition. Genetic analysis of the leptin gene indicated that a combination of three polymorphisms located at a 135 bp region of the leptin promoter explained most of the variance in prepartum leptin concentrations. The two extreme genotype combinations could be used to investigate the function of leptin concentrations in pregnant cows. A polymorphism located on intron 2 of the leptin gene explained a significant part of the variation in milk yield. On the promoter region of the leptin gene an SNP was detected that was associated with first postpartum luteal activity (FPLA). This SNP could be a candidate marker for fertility in dairy cows. Another SNP on the leptin promoter was associated with energy balance and dry matter intake (DMI) where a higher dry matter intake occurred together with a higher energy balance. Two genotype combinations of the aforementioned three associated SNPs were defined which had a good milk yield together with a good energy balance and fertility. Calculations of an economical value per trait have to validate if one of these genotype combinations would be a possible candidate to be used in selection.