Male fetuses negatively affect the vitality of the litter and the dam's metabolic and physiological state in multifetal pregnant ewe.

In sheep, ~30% of fetuses do not survive till parturition, and 17.7% of the multifetal pregnancies experience partial litter loss (PLL). In humans, multifetal pregnancies are associated with a higher risk of perinatal mortality. Therefore, the objectives were to examine the association between partial litter loss, fetal sex, dam's metabolic and physiological state, and pregnancy outcome in multifetal pregnant ewes. The study includes two parts. The first was a retrospective study, in which we analyzed data of 675 lambings and examined the PLL incidence according to male ratio (MR) for all litter sizes (range 2-6). Lambings were categorized as having a low male ratio (LMR; 50% males). In the second part, we monitored 24 ewes from 80 to 138 days in pregnancy every 10 days, and then daily until lambing, by ultrasound scanning for maternal heart rate (HR), and Doppler ultrasound for litter vitality. Blood samples were taken from dams on the days of scanning. Male ratio strongly affected PLL, where the general survival rate (for all lambings) was reduced from 90% in LMR lambings to 85% in HMR lambings. The odds ratio for PLL in HMR vs. LMR litters was 1.82. Birth body weight and the survival rate of female was higher in LMR than HMR lambings, with no differences for male lambs in both parameters. In the second part, dams' HR during the last trimester was 9.4% higher in LMR than in HMR pregnancies, with no differences in fetuses' HR. The plasma glucose and insulin concentrations were not significantly different between groups, but plasma β-hydroxybutyrate and nonesterified fatty acid concentrations were, respectively, 31% and 20% lower in HMR vs. LMR ewes. In conclusion, male fetuses negatively affect pregnancy outcomes and influence dams' metabolic and physiological state in sheep

Intravenous Infusions of Glycerol Versus Propylene Glycol for the Regulation of Negative Energy Balance in Sheep: A Randomized Trial

Negative energy balance (NEB) is a state of insufficient dietary-energy consumption, characterized by the breakdown of adipose fat to meet the physiological energy expenditure. Extensive NEB, as common in high-yielding transitioning ruminants, drives significant metabolic disturbance and pathologies such as pregnancy toxemia and ketosis. Strategies to minimize the severity of NEB include the use of energy-dense feed supplements, like glycerol and propylene glycol (PG), or IV glucose infusion during severe hypoglycemia. PG and glycerol have been studied mainly by oral or ruminal administration, which exposes them to substantial metabolism in the digestive system. To investigate their direct benefits to mitigating NEB, we intravenously infused them into sheep induced into NEB by feed restriction. Sixteen 5-month-old ewe lambs at NEB were IV-treated with 170 mL isotonic saline containing 15% glycerol or 15% PG. Both PG and glycerol effectively reduced hyperketonemia by 57% and 61%, and inhibited adipose lipolysis by 73.6% and 73.3%, respectively. Surprisingly, only glycerol was glucogenic (p < 0.0001) and insulinotropic (p < 0.0075), while PG was primarily utilized for production of lactate (p < 0.0001). Tissue-damage biomarkers indicated hemolytic activity for PG. This study revealed glycerol as a superior IV treatment for effective relief of NEB. Since it carries no risk of glucose overloading, glycerol IV infusion may also have clinical advantages over glucose for treatment of pregnancy toxemia and ketosis

Unveiling genomic regions that underlie differences between Afec-Assaf sheep and its parental Awassi breed

International audienceAbstractBackgroundSheep production in Israel has improved by crossing the fat-tailed local Awassi breed with the East Friesian and later, with the Booroola Merino breed, which led to the formation of the highly prolific Afec-Assaf strain. This strain differs from its parental Awassi breed in morphological traits such as tail and horn size, coat pigmentation and wool characteristics, as well as in production, reproductive and health traits. To identify major genes associated with the formation of the Afec-Assaf strain, we genotyped 41 Awassi and 141 Afec-Assaf sheep using the Illumina Ovine SNP50 BeadChip array, and analyzed the results with PLINK and EMMAX software. The detected variable genomic regions that differed between Awassi and Afec-Assaf sheep (variable genomic regions; VGR) were compared to selection signatures that were reported in 48 published genome-wide association studies in sheep. Because the Afec-Assaf strain, but not the Awassi breed, carries the Booroola mutation, association analysis of BMPR1B used as the test gene was performed to evaluate the ability of this study to identify a VGR that includes such a major gene.ResultsOf the 20 detected VGR, 12 were novel to this study. A ~7-Mb VGR was identified on Ovies aries chromosome OAR6 where the Booroola mutation is located. Similar to other studies, the most significant VGR was detected on OAR10, in a region that contains candidate genes affecting horn type (RXFP2), climate adaptation (ALOX5AP), fiber diameter (KATNAl1), coat pigmentation (FRY) and genes associated with fat distribution. The VGR on OAR2 included BNC2, which is also involved in controlling coat pigmentation in sheep. Six other VGR contained genes that were shown to be involved in coat pigmentation by analyzing their mammalian orthologues. Genes associated with fat distribution in humans, including GRB14 and COBLL1, were located in additional VGR. Sequencing DNA from Awassi and Afec-Assaf individuals revealed non-synonymous mutations in some of these candidate genes.ConclusionsOur results highlight VGR that differentiate the Awassi breed from the Afec-Assaf strain, some of which may include genes that confer an advantage to Afec-Assaf and Assaf over Awassi sheep with respect to intensive sheep production under Mediterranean conditions

Metabolic Effects of Vitamin B1 Therapy under Overnutrition and Undernutrition Conditions in Sheep

As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL−1 for CG, T5, and T10, respectively: p < 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p < 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism

Hyperglycemia-stimulating diet induces liver steatosis in sheep

Abstract Hepatic steatosis is strongly associated with chronic liver disease and systemic metabolic disorder. Adipose lipolysis is a recognized principal source of intrahepatic fat in various metabolic disorders, including non-alcoholic fatty liver disease. We hypothesized that, in the premorbid state, hepatic de novo lipogenesis (DNL) driven by excess carbohydrates abundance might play a more significant role. We employed a novel nutritional model in sheep of two distinct carbohydrates abundances. During 4 months of the dietary treatment, lambs were monitored for metabolic and terminal liver parameters. Lambs grown on the high-calorie (HC) diet were consistently more hyperglycemic and hyperinsulinemic than lambs grown on the lower-calorie (LC) diet (P < 0.0001). As a result, the HC lambs developed systemic- (HOMA-IR of 7.3 vs. 3.1; P < 0.0001), and adipose- (ADIPO-IR of 342.7 vs. 74.4; P < 0.0001) insulin resistance, significant adiposity (P < 0.0001), and higher plasma triglycerides (P < 0.05). Circulating leukocytes in the HC lambs had higher mRNA expression levels of the proinflammatory markers CCL2 (P < 0.01) and TNF-alpha (P < 0.04), and IL1B trended higher (P < 0.1). Remarkably, lambs on the HC diet developed substantial liver steatosis (mean fat content of 8.1 vs. 5.3% in the LC group; P < 0.0001) with a higher histological steatosis score (2.1 vs. 0.4; P < 0.0002). Hepatic steatosis was most-strongly associated with blood glucose and insulin levels but negatively correlated with circulating fatty acids—indicating a more significant contribution from hepatic DNL than from adipose lipolysis. Sheep may prove an attractive large-animal model of fatty liver and metabolic comorbidities resulting from excess carbohydrate-based energy early in life

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Additional file 7. Candidate gene sequences. This file contains sequences of candidate genes in a FASTA-like format. Each sequence header consists of the gene symbol followed by its reference GenBank accession number and the breed name. Polymorphic nucleotide positions are indicated in blue and red font colors

MOESM2 of Unveiling genomic regions that underlie differences between Afec-Assaf sheep and its parental Awassi breed

Additional file 2: Table S2. Genomic relationship within and between local Awassi flocks

MOESM8 of Unveiling genomic regions that underlie differences between Afec-Assaf sheep and its parental Awassi breed

Additional file 8: Figure S2. Variability in fat-tail phenotypes in Assaf sheep. Awassi-like fat tail (A). Fat tails with different amounts of fat deposition and different lengths (B to H)