Analysis of fecal microbiome and metabolome changes in goats with pregnant toxemia.

BACKGROUND: Pregnancy toxemia is a common disease, which occurs in older does that are pregnant with multiple lambs in the third trimester. Most of the sick goats die within a few days, which can seriously impact the economic benefits of goat breeding enterprises. The disease is believed to be caused by malnutrition, stress, and other factors, that lead to the disorder of lipid metabolism, resulting in increased ketone content, ketosis, ketonuria, and neurological symptoms. However, the changes in gut microbes and their metabolism in this disease are still unclear. The objective of this experiment was to evaluate the effect of toxemia of pregnancy on the fecal microbiome and metabolomics of does. RESULTS: Eight pregnant does suspected of having toxemia of pregnancy (PT group) and eight healthy does during the same pregnancy (NC group) were selected. Clinical symptoms and pathological changes at necropsy were observed, and liver tissue samples were collected for pathological sections. Jugular venous blood was collected before morning feeding to detect biochemical indexes. Autopsy revealed that the liver of the pregnancy toxemia goat was enlarged and earthy yellow, and the biochemical results showed that the serum levels of aspartate aminotransferase (AST) and ß-hydroxybutyric acid (B-HB) in the PT group were significantly increased, while calcium (Ca) levels were significantly reduced. Sections showed extensive vacuoles in liver tissue sections. The microbiome analysis found that the richness and diversity of the PT microbiota were significantly reduced. Metabolomic analysis showed that 125 differential metabolites were screened in positive ion mode and enriched in 12 metabolic pathways. In negative ion mode, 100 differential metabolites were screened and enriched in 7 metabolic pathways. CONCLUSIONS: Evidence has shown that the occurrence of pregnancy toxemia is related to gut microbiota, and further studies are needed to investigate its pathogenesis and provide research basis for future preventive measures of this disease.

Comparison of blood ΒHBA measurement devices for diagnosis of subclinical pregnancy toxaemia in sheep: A field study.

Pregnancy toxaemia is a serious disease that occurs during the last trimester of pregnancy in sheep. Yet, in most cases, the disease may have a subclinical course. This study was aimed at comparing blood ßHBA measurement devices for diagnosis of subclinical pregnancy toxaemia in late pregnant sheep. In the study, a total of 50 blood samples were collected from Romanov (n = 30) and cross-bred Hamdani (n = 20) sheep. Blood ßHBA levels were measured using TaiDoc TD-4235 and CentriVet ßHBA hand-held meter. Randox ßHBA (Ranbut) assay was used as a reference laboratory method to compare hand-held meters. ßHBA value of 0.8 mmol/L was set as the cut-off value for diagnosis of subclinical pregnancy toxaemia. Statistical analyses were carried out using Minitab 21 and Jamovi software. In the study, the correlation of Randox-TaiDoc TD-4235 and Randox-CentriVet was .822 (p < .001) and .728 (p < .001), respectively. Based on the Ranbut assay, nine ewes out of 50 were diagnosed with subclinical pregnancy toxaemia. Specificity (detection of healthy ewes) and sensitivity (detection of ewes with subclinical pregnancy toxaemia) for TaiDoc TD-4235 and CentriVet hand-held meters were 100%, 77.8%, and 100%, 66.7%, respectively. In the receiver operating characteristic (ROC) analysis, areas under the ROC curve (AUC) were 0.976 and 0.920 for TaiDoc and CentriVet, respectively. Bland-Altman analysis revealed a bias of 0.092 mmol/L for TaiDoc and a bias of 0.132 mmol/L for CentriVet. TaiDoc hand-held meter shows a better correlation with the Randox Ranbut assay and greater sensitivity compared to the CentriVet hand-held meter. In conclusion, both TaiDoc and CentriVet hand-held meters can be securely used in the diagnosis of subclinical pregnancy toxaemia in sheep. For these reasons, subclinical pregnancy toxaemia and these devices will be evaluated within the scope of herd management programme in the sheep industry. It should also be taken into account that these conditions will affect the future fertility of the mother and offspring.

Assisted reproductive technologies induce temporally specific placental defects and the preeclampsia risk marker sFLT1 in mouse.

Although widely used, assisted reproductive technologies (ARTs) are associated with adverse perinatal outcomes. To elucidate their underlying causes, we have conducted a longitudinal analysis of placental development and fetal growth using a mouse model to investigate the effects of individual ART procedures: hormone stimulation, in vitro fertilization (IVF), embryo culture and embryo transfer. We demonstrate that transfer of blastocysts naturally conceived without hormone stimulation and developed in vivo prior to transfer can impair early placentation and fetal growth, but this effect normalizes by term. In contrast, embryos cultured in vitro before transfer do not exhibit this compensation but rather display placental overgrowth, reduced fetal weight, reduced placental DNA methylation and increased levels of sFLT1, an anti-angiogenic protein implicated in causing the maternal symptoms of preeclampsia in humans. Increases in sFLT1 observed in this study suggest that IVF procedures could increase the risk for preeclampsia. Moreover, our results indicate that embryo culture is the major factor contributing to most placental abnormalities and should therefore be targeted for optimization.

Serum concentrations of folic acid and cobalamin and energy metabolism of ewes as a function of the energy density of the diet, peripartum period, and pregnancy toxemia.

The aim of this study was to determine the serum levels of folic acid, cobalamin, and indicators of energy metabolism during the peripartum period of ewes submitted to different diets and with or without pregnancy toxemia. Forty Santa Inês ewes were divided into three groups, a group of 20 animals fed only roughage-diet with low energy density (G1), a group of 10 ewes submitted to diet containing roughage and concentrate-diet with high energy density (G2), and a group of 10 ewes with diagnosis of pregnancy toxemia (PT) (G3). In the ewes of groups G1 and G2, blood samples were collected -30, -15, -7 days pre-partum, on the day of partum, and 7, 15, and 30 days postpartum; blood samples from G3 animals were collected during the veterinary clinic care. Significant variations were observed in the plasma concentration of glucose and serum folic acid, cobalamin, fructosamine, NEFA, and ß-hydroxybutyrate in the groups fed diets with different energy levels, with and without PT (P < 0.05). A positive correlation of folic acid and cobalamin was observed with plasma glucose and serum NEFA concentrations, in addition to negative correlation of glucose with NEFA and ß-hydroxybutyrate and positive correlation between the latter biomarkers of energy metabolism. The ewes diagnosed with PT showed higher levels of folic acid, NEFA, and ß-hydroxybutyrate (P < 0.05). Ewes fed diet containing roughage and concentrate present higher serum levels of folic acid, cobalamin, and glucose, in the pre-partum period and in the lactation period. The results obtained contribute to better understanding of the application of blood concentration tests for folic acid and cobalamin in the energy metabolism and in PT in ewes.

Evaluation of metabolic and oxidative profile in ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of disease.

This study was conducted on ewes with pregnancy toxemia (PT) with an attempt to evaluate metabolic and oxidative profile in subclinical and clinical ovine pregnancy toxemia and to determine their association with diagnosis and prognosis of the disease. A total of 20 ewes having beta-hydroxy butyric acid (ß-HBA) > 2.5 mmol/L and proven clinical sings of PT, categorized as clinical PT (CPT); 12 ewes having ß-HBA 0.8-2.5 mmol/L and no clinical signs of PT, categorized at subclinical PT (SPT); and 10 ewes having ß-HBA ≤ 0.8 mmol/L, categorized as healthy control (CON) were enrolled. Among 20 CPT ewes, 11 had negative outcomes (non-survivors), six ewes had positive outcomes (survivors), and three were lost during follow-up. A significant increase in non-esterified fatty acid, ß-HBA, triglycerides, gamma-glutamyl transferase, lactate dehydrogenase, and malondialdehyde levels and a significant decrease in fructosamine were observed in CPT and SPT compared to CON. A significant increase in cholesterol, aspartate amino transferase, and creatinine kinase and a significant decrease in albumin, potassium, calcium, superoxide dismutase, and catalase were observed in CPT only. Glucose was significantly decreased in SPT only. The highest area under the curve (AUC) was observed for fructosamine (89.7% and 87.5% for CPT and SPT, respectively) with the optimum cutoff point calculated on the basis of maximum sensitivity (SE) and specificity (SP) being 0.607 mmol/L (SE: 89.3% and SP: 72.2%) and 1.005 mmol/L (SE: 90.0% and SP: 75.3%) for CPT and SPT, respectively. At the cutoff limit of 0.607 mmol/L and 1.005 mmol/L, the odds ratio was 10.8 and 8.0 for CPT and SPT, respectively. A significant decrease in fructosamine and potassium and a significant increase in creatinine, lactate dehydrogenase, and malondialdehyde were observed in non-survivors compared to survivors. It was thus concluded that fructosamine was the best diagnostic indicator of both CPT and SPT followed by non-esterified fatty acid. Fructosamine, creatinine, potassium, lactate dehydrogenase, and malondialdehyde were the best prognostic indicators of PT.

The distinctive short-term response of late-pregnant prolific ewes to propylene glycol or glycerol drenching.

Pregnancy toxemia is the most frequent metabolic disorder of ewes in late pregnancy. Although propylene glycol (PG) and glycerol (GLY) are common glucogenic supplements for treating pregnancy toxemia in ewes, the relative benefit of these 2 supplements is not entirely clear. Therefore, the objectives of the present study were to determine the changes during 24 h in key blood metabolites and insulin in response to PG or GLY drenching in prolific ewes. To this end, 36 multiparous late-pregnant Afec-Assaf ewes (∼132.4 d pregnant) bearing 2 to 4 fetuses, divided into 2 blocks (18 ewes in each block), with a blood ß-hydroxybutyrate (BHB) concentration of 0.5 to 1.6 mmol/L were included. Ewes were divided into 3 groups (12 ewes each; 6 ewes in each experimental day), according to their BHB levels, expected litter size, body weight, and body condition score, and were drenched with the following: (1) control group (CTL), 55 mL of water; (2) PG, 106 mL of PG (100% PG, 448 calories); or (3) GLY, 108 mL of Koforin 80 (80% GL; 448 calories). Blood samples were taken before drenching and every hour after drenching for 24 h. Plasma concentration of glucose, BHB, nonesterified fatty acids, lactate, glycerol, and insulin were determined. Because there were no effects of treatments after 12 h in the first block, the data were analyzed for 12 h after drenching rather than 24 h. The plasma glucose concentration during the first 5 h after drenching was the highest in the GLY, BHB concentration was the lowest in the PG, and the nonesterified fatty acid levels were lower in the PG compared with the CTL ewes during the first 5 h after drenching. However, glucose concentration was higher in the PG ewes at 9, 11, and 12 h after drenching than in CTL or GLY ewes. The mean lactate concentration in plasma for 12 h was 2.5- and 1.9-fold higher in the PG compared with the CTL and GLY ewes, respectively, and except at 11 h after drenching, it was significantly higher at each time point. The insulin concentration was higher in the GLY than in both other groups at 2 to 5 h after drenching. These results suggest that during the first few hours after drenching the effect of PG was more effective in reducing the BHB concentration, whereas the GLY effect was more effective in enhancing glucose concentration. The increased concentration in lactate following PG treatment suggests that the PG contribution to gluconeogenesis is mediated through its metabolism to lactate. In contrast, the lack of an effect on lactate, and the faster increase in blood glucose in response to GLY suggest that GLY has a more advanced entry point to gluconeogenesis, which influences the immediate response in enhancing the glucose blood concentration.

Evaluation of a fibrate, specific stimulant of PPARα, as a therapeutic alternative to the treatment of clinical ovine pregnancy toxaemia.

Ovine pregnancy toxaemia is a metabolic disorder affecting sheep in their last 6 weeks of pregnancy as a result of their inability to maintain adequate energy homoeostasis. Different alternative treatments are available with variable results. The aim of this research was to evaluate a peroxisome proliferator-activated receptor alpha (PPARα) stimulant as an alternative to treat clinical pregnancy toxaemia. Thirty-three adult sheep, with known gestation date and carrying a single foetus, were fasted from day 130 of gestation until animals showed clinical disease. From that moment onwards, sheep were treated during 6 days with three different therapeutic alternatives: 10 mg/kg of 2-methyl-2-phenoxy-propionic acid; 10 mg/kg of 2-methyl-2-phenoxy-propionic acid + 100 mL of propylene glycol oral; or 100 mL of propylene glycol oral. Glycaemia and serum ß-hydroxybutyrate (BHOB) were determined daily. Liver biopsies were taken at day 130 of gestation, at the beginning and end of treatments and at 5 days postpartum, evaluating the extent and degree of the steatosis lesion. Even though in sheep treated with 2-methyl-2-phenoxy-propionic acid, serum concentrations of glucose and BHOB recovered more slowly, we conclude that 2-methyl-2-phenoxy-propionic acid alone or combined with propylene glycol can be used as an alternative to effectively treat fatty liver, and therefore pregnancy toxaemia.

Glucose intolerance in dairy goats with pregnancy toxemia: Lack of correlation between blood pH and beta hydroxybutyric acid values.

This study assessed the response to a glucose tolerance test in dairy goats with pregnancy toxemia (PT), in healthy, pregnant, non-lactating dairy goats in the last month of gestation (HP), and in healthy, lactating, non-pregnant, dairy goats in mid-lactation (HL). A 500 mL volume of a 5% glucose solution was administered by the IV route. Blood glucose concentrations returned to pre-infusion levels by 90 min in all 8 HL goats, and by 180 min in all 8 HP goats. In contrast, concentrations of blood glucose were still significantly above pre-infusion levels at 180 min post-infusion in all 8 PT goats. Thus, marked glucose intolerance was demonstrated in the PT goats, and mild intolerance was noted in the HP goats. In 25 goats diagnosed with PT and having blood beta hydroxybutyric acid (BHBA) values ≥ 2.9 mmol/L, the correlation coefficient for BHBA with blood pH was non-significant.

Intolérance au glucose chez les chèvres laitières atteintes de toxémie gestationnelle : absence de corrélation entre les valeurs du pH sanguin et de l'acide bêta-hydroxybutyrique. Cette étude a évalué la réponse à un test de tolérance au glucose chez des chèvres laitières atteintes de toxémie gestationnelle (TG), chez des chèvres laitières gravides en santé qui n'étaient pas en lactation durant le dernier mois de la gestation (HP) et chez des chèvres laitières non gravides en santé en pleine lactation (HL). Un volume de 500 mL d'une solution de glucose à 5 % a été administrée par voie IV. Les concentrations de glucose sanguin sont retournées à la normale dans un délai de 90 minutes chez les huit chèvres HL et dans un délai de 180 minutes chez les huit chèvres HP. Par contraste, les concentrations de glucose sanguin étaient toujours significativement supérieures aux niveaux de pré-infusion 180 minutes après l'infusion chez les huit chèvres TG. Par conséquent, une intolérance au glucose marquée a été démontrée chez les chèvres TG et une intolérance légère a été observée chez les chèvres HP. Chez les 25 chèvres diagnostiquées avec la TG qui présentaient des valeurs sanguines d'acide bêta-hydroxybotyrique (BHBA) de ≥ 2,9 mmol/L, le coefficient de corrélation pour les BHBA avec le pH sanguin n'était pas significatif.(Traduit par Isabelle Vallières).

Ketonemia in dairy goats: effect of dry period length and effect on lying behavior.

In dairy animals, a successful transition from one lactation to the next includes minimizing negative energy balance. Cows experiencing excessive negative energy balance typically develop metabolic complications following parturition (e.g., ketosis); does are also susceptible before kidding (e.g., pregnancy toxemia). It is not known to what extent the provision and the length of the dry period affect these conditions in does. Furthermore, whereas clinical symptoms of these conditions include lethargy, behavioral changes resulting from ketosis and pregnancy toxemia have not been quantified in small ruminants. The aims of this study were to (1) describe the relationship between the dry period and negative energy balance, and (2) determine if lying behavior changes are indicative of the metabolic status of dairy goats. A total of 420 does on 10 commercial dairy goat farms in southern Ontario, Canada, were enrolled in the study (mean ± SD: 42±18 does/farm). Each doe was affixed with a data logger to measure lying behavior from 12 d before to 12 d after kidding. Blood samples were collected at least once before and at least once following kidding to determine blood ß-hydroxybutyrate (BHBA) concentration as an indicator of negative energy balance. Does were categorized as healthy (HLTH; both pre- and postkidding samples BHBA <0.9 mmol/L), PREGTOX (prekidding BHBA ≥1.7 mmol/L), or KET (postkidding BHBA ≥1.7 mmol/L). Behaviors were analyzed according to 5 periods: P-2 (d -12 to d -2 relative to kidding), P-1 (d -1 relative to kidding), P0 (d 0, kidding day), P1 (d 1 relative to kidding), and P2 (d 2 to 12 relative to kidding). Dry period length and milk production after kidding were recorded when available. Farms ranged from 0 to 15% and 0 to 50% in prekidding and postkidding ketonemia, respectively. The HLTH does had shorter dry periods compared with PREGTOX and KET does (43 vs. 55 d, SE of the differences of means=4 d). One farm kept some does milking, while drying off others; on this farm more PREGTOX and KET does (11/28) were found in the dry group versus the continuously milked group (1/16). Overall, does that had ketonemia before kidding (PREGTOX) spent more time lying down compared with healthy does (16.1 vs. 12.7 h/d, SE of the differences of means=0.9). Both PREGTOX and HLTH does had increased lying bouts in P-2 compared with the day before (P-1) kidding [(mean (95% CI): 16.8 (15.8-17.8) vs. 20.5 (19.4-21.8) bout/d]. Compared with HLTH does, animals that were ketonemic following kidding (KET) had higher mean lying times throughout the study (14.5 vs. 13.5 h/d, SE=0.4). Previous work has shown a relationship between shorter and skipped dry periods and improved energy balance in dairy cows; the current study is the first to indicate a similar relationship in dairy goats. Furthermore, goats that developed ketonemia, particularly before kidding, displayed decreased activity, including longer lying times and fewer lying bouts in the days around kidding.

Ultrasonographic findings in the ovine udder during lactogenesis in healthy ewes or ewes with pregnancy toxaemia.

Objective of the study was to record, by means of ultrasonographic examination, changes occurring during lactogenesis in the udder of healthy ewes and of ewes with pregnancy toxaemia. The work was carried out in 28 ewes, 16 with pregnancy toxaemia (group A) and 12 healthy controls (group B). B-mode and Doppler ultrasonographic examination of the udder of ewes was performed. During the last month of pregnancy, grey-scale intensity values of mammary parenchyma in group A were significantly greater than in group B (P = 0.007), as was also the progressive increase in grey-scale intensity values in both groups (P < 0.001). Blood mammary input was significantly greater in ewes of group B than in ewes of group A (P < 0.05), as was also the progressive increase in blood input in both groups (P < 0.001). Further, differences between the two groups were identified in pulsatility index (P = 0.007) and in mean blood velocity (P = 0.036), but only during the last fortnight of pregnancy. After lambing, grey-scale values decreased sharply compared to those in pregnancy (P < 0.01), whilst blood input, pulsatility index and mean blood velocity continued the same trend as at the last stage of pregnancy, with differences between the two groups still prevalent (P < 0.05). There was a reverse correlation between grey-scale intensity values and milk quantities (P < 0.035) and a correlation between blood input and milk quantities (P < 0.07). The progressive increase in the diameter of the external pudendal artery was significant (P < 0.001), but no significant differences were evident between the two groups (P > 0.35). Differences between group A and group B in all other haemodynamic parameters studied were not significant, neither throughout the last month of pregnancy (P > 0.25), nor during the first week of lactation (P > 0.06). However, their progressive changes during the last month of pregnancy were significant (P < 0.02).

Changes in free amino acid profile in goats with pregnancy toxemia.

Pregnancy toxemia is a metabolic disorder that afflicts goats when the heightened energy requirements preceding parturition are not sufficiently satisfied. At present, the potential association between pregnancy toxemia and the free amino acid composition in hair goats remains uncharted territory. The purpose of this study is to investigate the free amino acid profile in goats during the pivotal three weeks preceding delivery, distinguishing among those with subclinical pregnancy toxemia (SPT), clinical pregnancy toxemia (CPT), and those in the control group (CG). Additionally, the study aims to investigate any potential relationship between the amino acid profile and beta hydroxy butyric acid (BHBA) levels. The researchers analyzed a total of 50 goats, comprising 20 goats with SPT, 20 with CPT, and 10 in the CG. The serum free amino acid profile was determined using a gas chromatography flame ionization detector (GC-FID) device. BHBA concentration in goats with CPT and SPT was significantly higher than KG (p < 0.001). Furthermore, in goats with CPT, the glucose concentration was significantly lower than in CG (p < 0.012). In goats with CPT and SPT, the concentration of valine, one of the gluconeogenic amino acids, was significantly higher than in control group (p < 0.001), while histidine concentration was significantly lower (p < 0.020) than in control group. Specifically in goats with CPT, the concentrations of alanine (p < 0.002), serine (p < 0.001), and threonine (p < 0.043) were significantly lower than in control group. Moreover, the concentration of phenylalanine, which is both a glycogenic and ketogenic amino acid, was significantly lower (p < 0.028) in goats with SPT compared to the control group. The Fisher ratio (p < 0.010) and Glycine/Alanine ratio (p < 0.001) were significantly higher in pregnancy toxemia goats with than in control group goats, indicating a poor nutritional and energy status of the goats during the prepartum period. In summation, the findings of this study underscore that amino acids exhibiting marked concentration variations hold considerable promise in the diagnosis, prognosis, and therapeutic management of pregnancy toxemia.

Association of vitamin D status with redox balance and insulin resistance and its predicting ability for subclinical pregnancy toxemia in pregnant sheep.

The study aimed to evaluate the role of vitamin D on redox balance, insulin resistance and its predicting value for subclinical pregnancy toxemia (SPT) in pregnant ewes. At four weeks pre-lambing, fifteen healthy pregnant ewes were divided into two groups, ewes with sufficient vitamin D (25-hydroxy-vitamin D (25VitD) (SVD, n = 9) and ewes with insufficient 25VitD (ISVD, n = 6). Blood samples were collected at 4 weeks pre-lambing using modified frequently sampled intravenous glucose tolerance test for the estimation of various metabolites. The baseline glucose, insulin, non-esterified fatty acid (NEFA), fructosamine, beta-hydroxy butyric acid (ß-BHA), calcium, phosphorus concentration and total oxidant status (TOS) did not differ significantly between the two groups, however, total antioxidant capacity (TAC) was significantly (p = 0.031) low in ISVD ewes. Area under the curve for glucose, insulin, elimination rate of glucose and peak insulin also did not differ significantly between the two groups. Correlation analysis revealed, positive association of 25VitD with fructosamine, calcium and TAC, and negative correlation with NEFA and TOS. Subsequent blood sampling at 2 weeks pre-lambing and at lambing showed significant difference in NEFA (p = 0.001), ß-HBA (p = 0.001), and fructosamine(p = 0.012) between the two groups. A significant time x group interaction was observed in NEFA (p = 0.019), ß-HBA (p = 0.031), and fructosamine (p = 0.026) concentration. The NEFA concentrations were increased and fructosamine decreased at 2 weeks pre-lambing and at lambing along with significantly increased ß-HBA at 2 weeks pre-lambing in ISVD compared to SVD. Taking 0.8 mmol/L ß-HBA as the cut off limit for SPT, ISVD ewes had higher odds of developing SPT two weeks prior to lambing (OD 16.00; p = 0.042) and at lambing (OD 10; p = 0.077). This study concludes that 25VitD significantly influence redox balance and energy profile and serves as a valuable predictor for SPT in pregnant sheep.

Post-glucose load changes of plasma key metabolite and insulin concentrations during pregnancy and lactation in ewes with different susceptibility to pregnancy toxaemia.

Insulin resistance during late gestation may act as a predisposing factor of ovine pregnancy toxaemia (OPT). To evaluate the insulin action on energy metabolism in ewes with different susceptibilities to OPT, intravenous glucose tolerance tests (1 mmol glucose/kg body weight) were performed in 5.6 ± 0.7 year old, slightly underfed German Blackheaded Mutton ewes [high-risk (HR) ewes] and 2.5 year old, overnourished Finnish Landrace ewes [low-risk (LR) ewes] during mid and late pregnancy, during early lactation and during the dry period. Plasma samples were analysed for glucose, insulin, non-esterified fatty acids (NEFA) and ß-hydroxybutyrate (ß-HB). The glucose elimination rate and the glucose-stimulated first-phase insulin secretion were significantly (p < 0.05) lower in the HR, in relation to the LR group combining the data of all gestational stages. The basal rate of lipolysis was significantly increased in the HR ewes during late pregnancy, but the NEFA clearance after the glucose load was similar in both groups during all reproductive stages. Plasma ß-HB concentrations decreased only in the LR ewes after the glucose load during late pregnancy. Results indicate an insulin resistance in the HR ewes regarding the glucose utilization and the ketone body formation during late pregnancy. The insulin resistance in the HR ewes may represent one predisposing factor responsible for the susceptibility to OPT. Further scientific work is necessary to elucidate whether this insulin resistance was due to breed, age or nutritional state.

Pregnancy Toxemia Therapeutic Options.

This review covers the treatment options for pregnancy toxemia in small ruminants. Clinical assessment and detection of underlying metabolic and electrolyte derangements direct resuscitation efforts and provide prognostic indications. Treatment programs are dependent on producer goals and case specifics. Options include oral glucogenic precursors (eg, propylene glycol, glycerol), intravenous glucose solutions, insulin, and other supportive care measures. Induction of parturition or C-section is often carried out to minimize ongoing energy deficits, with variable survival rates. Prolonging gestation to maximize fetal viability often requires intensive care in a hospital setting and carries significant risk to both dam and offspring.

Pulse wave Doppler ultrasound of umbilical cord in experimentally induced pregnancy toxemia in sheep.

Contrary to its widespread use in human cases, the use of Doppler ultrasonography is only recently becoming prevalent in farm animals. This study aimed to determine the effects of maternal metabolic and clinical changes on fetal hemodynamics during pregnancy toxemia with the doppler examination of umbilical cord. In the study twenty ewes with a single healthy fetus were included in the study. At the end of the 120th day of pregnancy, 20 single-bearing pregnant ewes were randomly categorized into two groups. Ewes in the control group were fed to meet all nutritional requirements. On the other contrary, the experimental ewes were fed to meet equivalent to 50 % of the daily needs and then fasted for 96 h. Doppler ultrasonographic examinations of umbilical cord were performed once every two days and once a day during fasting. Beta hydroxybutyric acid (BHBA) concentration was measured by taking blood from sheep on examination days. Pulse systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, pulsatility index (PI), resistance index (RI), and fetal heart rate (FHR) as well as BHBA values and how those parameters has changed over time (time by treatment effect) due to energy deprivation during pregnancy were evaluated using repeated measure analysis of variance. No clinical signs were observed in both toxemia and control groups during restricted feeding. BHBA concentration increased and there was a significant time, time by treatment and main effect of treatment effect between groups. No significant main effect of treatment and time by treatment interaction was observed in the changes of PI, RI, FHR, and systolic/diastolic velocity values over time in both groups. FHR was reduced over time, and there was a significant time effect in FHR in both groups. Although doppler indices didn't increase, both PSV and EDV values increased significantly in the pregnancy toxemia group compared with the controls (Time P = 0.03, time by treatment interaction P < 0.05) and the main effect of treatment P < 0.05). The marked increase in blood velocities (PSV and EDV) in the umbilical cord is probably due to the compensatory functioning for excessive energy deprivation of the fetus. Therefore, PSV and EDV might be a valuable indicator for evaluating the fetus's health status during the management of the PT.

Pregnancy Toxemia in Sheep and Goats.

Pregnancy toxemia is a common metabolic disease of late pregnant ewes and does, which potentially has devastating impacts on health and performance. This metabolic syndrome is not only one of over conditioned animals but is more typically associated with inadequate energy intake to support pregnancy requirements leading to body protein and fat mobilization. Blood chemistries provide insight into diagnosis and possibly may predict responsiveness to treatment and outcome. Early recognition of the disease with appropriate intervention is the best approach to minimizing the impact of this disease in the sheep flock or goat herd.

Causes of abortion in Iranian sheep flocks and associated risk factors.

Abortion is a major issue in sheep husbandry. It can result in significant economic losses and a severe public health risk. This survey assessed the infectious and non-infectious causes of abortion in Iranian sheep flocks and determined the main risk factors. In this cross-sectional survey, causes of abortion were evaluated in 757 sheep flocks, and risk factors were analysed. A checklist containing general animal information for each abortion outbreak evaluated was filled in. Data were analysed using univariate tests and multivariable binary logistic regression analysis. In this sense, parity, gestational age of the aborted fetus, vaccination protocol, mineral supplementation and history of stillbirth showed significant associations with abortion. Infectious agents such as Coxiella burnetti (22.7%), Chlamydia abortus (12.3%) and Brucella melitensis (10.4%) were the most frequently isolated in the investigated flocks, with more than 2% of abortion rates. On the other hand, non-infectious agents such as trauma, pregnancy toxaemia and vitamin E/Se deficiency were involved in those flocks with low abortion rates (less than 10%). Results revealed multiple causes of abortion outbreaks among Iranian sheep flocks, which need careful investigation to identify possible aetiology and risk factors. Further studies are necessary to evaluate if these factors are similar to other countries in the same region.

Characterization of short- and long-term morbidity and mortality of goat kids born to does with pregnancy toxemia.

BACKGROUND: Pregnancy toxemia is a common metabolic disease of periparturient small ruminants. Information on its effects on metabolism and perinatal adaptation of newborn lambs and kids is lacking. OBJECTIVES: Evaluate differences in morbidity, mortality, and common biochemical and hematologic variables between pregnancy toxemia kids (PT) and control kids (CON). ANIMALS: Sixteen kids born to does being treated at the hospital for pregnancy toxemia (blood beta-hydroxybutyrate concentration [BHB] > 1.2 mmol/L) and 12 kids from healthy dams (dam BHB < 1.2 mmol/L) that kidded at the hospital. METHODS: In this cohort study, serial measurements of blood L-lactate, glucose, and BHB concentrations, arterial blood gases, hematocrit, total protein concentrations, nonesterified fatty acids (NEFAs) concentrations, and body weight were compared between groups over the first 72 hours of life. Long-term follow-up was performed after 3 months. RESULTS: Pregnancy toxemia kids were more likely to require tube feeding at 0 and 12 hours (relative risk 7.7 [1.13, 52.45] and 2.8 [1.39, 5.65]). Pregnancy toxemia kids were more acidemic (7.26 ± 0.069 vs 7.34 ± 0.079, P = .003) and hyperlactatemic (8.17 ± 2.57 vs 5.48 ± 2.71, P = .003) at birth than CON kids. Control kids were 1.1 [1.01, 1.77] times more likely to survive to discharge and 2.2 [1.15, 4.20] times more likely to survive to 3 months than PT kids. CONCLUSIONS AND CLINICAL IMPORTANCE: Pregnancy toxemia kids had higher short- and long-term mortality and were more likely to require perinatal intervention. Weight loss in the first few days could be a useful predictor of nonsurvival.

BHBA regulates the expressions of lipid synthesis and oxidation genes in sheep hepatocytes through the AMPK pathway.

Pregnancy toxemia (PT) is the most frequent metabolic disease of sheep during late pregnancy, which can lead to enormous economic losses in sheep farm industry. However, the underlying mechanism of PT in sheep has not been fully elucidated. High levels of ß-hydroxy butyric acid (BHBA) exist in PT sheep. The AMP-activated protein kinase (AMPK) pathway plays a major role in regulating liver function. The aim of this study was to explore the effects of gradient concentrations of BHBA on lipid metabolism of sheep hepatocytes and the underlying molecular mechanism in vitro. The results showed that 0.6, 1.2 mmol/L BHBA could activate AMPKα, promoted the expressions of peroxisome proliferator-activated receptor alpha (PPARα) and its target genes, and inhibited the expressions of sterol regulatory element binding protein-1c (SREBP-1c) as well as its downstream genes. When the concentration of BHBA was beyond 1.2 mmol/L, the expressions of the above-mentioned proteins and genes were just the opposite. However, the expressions of adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) did not change significantly. The levels of very low density lipoprotein (VLDL), triglyceride (TG) and cholesterol (T-CHOL) showed a gradually increasing trend with the increase of BHBA concentration. According to the results above, it demonstrates that high levels of BHBA can inhibit the expression of the AMPK pathway and cause lipid metabolism disorders in sheep hepatocytes, which may lead to the occurrence of PT.

Changes in cardiac biomarkers in goats naturally affected by pregnancy toxemia.

Pregnancy toxemia (PT) is considered one of the most common metabolic diseases with high impact on the production of small ruminants. The objective of this study was investigate possible myocardial damage in goats affected with PT by the determination of serum myocardial biomarkers CK-MB and cTnI. A total of 44 goats affected with PT, and 10 apparently healthy goats (control group or CG) were used in the study. In goats with PT, the serum concentrations of cTnI (0.43 ng/mL) were significantly higher than that in CG goats (0.06 ng/mL). Although CK-MB showed no significant difference, it was approximately three times higher in animals with PT. The serum concentrations of insulin were significantly lower in PT goats (5.03 ppmol/L) compared to CG goats (10.66 pmol/L). The serum concentrations of cortisol in PT goats (155.41 nmol/L) were significantly higher than that in CG goats (36.58 nmol/L). Results of this study indicate that a clinically significant myocardial damage might occur in goats affected with PT leading to significant elevations in values of cTnI and CK-MB. Therefore, these parameters could be used as a potential prognostic indicator in goats affected with this important disease.