Irritable bowel syndrome in celiac disease - relationships to celiac disease antibodies and levels of pro-inflammatory cytokines.

BACKGROUND: Evidence indicates that low-grade inflammation can alter gastrointestinal motor and sensory function and might contribute to the genesis of symptoms in IBS. OBJECTIVE: To examine relationships between IBS, disease antibodies and cytokine titers in celiac patients and a control group. MATERIALS AND METHODS: IBS, CD activity and serum levels of IL-6, IL-8 and IL12/23p40 were determined in celiac patients and controls. RESULTS: 123 celiac patients were included, 89% were female. 59% demonstrated disease activity and 32% met IBS criteria. Prevalence of IBS was not different between patients who adhered or did not adhere to GFD as well as between patients with or without positive antibodies. Celiac patients had increased levels of IL-6, IL-8 and IL12/23p40 as compared to controls. Higher levels of cytokines were found in celiac patients with IBS than in those without IBS. No difference in levels of cytokines was found between patients with and without CD positive antibodies. A significant negative correlation between the mental component of QoL and IL-6 and IL12/23p40 levels was found, but not with IL-8. CONCLUSION: Higher levels of inflammatory cytokines were found in CD patients with IBS than in either those without IBS or controls, indicating that IBS symptoms are associated with an increase in the inflammatory response and a decrease in quality of life of CD patients. These differences in cytokine levels were not related to CD antibodies status suggesting that IBS, in CD, is related to a different inflammatory process than that which is relevant to CD.

Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Placental Gene Expression and Fetal Antioxidant Status, DNA-Methylation and Phenotype.

The use of polyphenols is a promising strategy for preventing or alleviating intrauterine growth restriction (IUGR) because polyphenol supplementation increases plasma antioxidant capacity and improves oxidative stress at the feto-placental unit; which are recognized as main issues in IUGR. However, there is a scarcity of experimental data on both realistic benefits and potential hazards of polyphenol supplementation during gestation. Hence, we aimed to use a swine model of IUGR pregnancy to determine possible effects of maternal supplementation with polyphenols (hydroxytyrosol) on placental expression of genes involved in antioxidant homeostasis, vascularization and fetal growth and thus on antioxidant status, DNA-methylation and phenotypic traits (morphology and homeostasis) of the fetus. Hydroxytyrosol improves placental gene expression and fetal antioxidant status and glucose metabolism in a sex-dependent manner, in which males were favored in spite of developmental failures. Concomitantly, hydroxytyrosol prevented hypomethylation of DNA associated with oxidative stress. Finally, no major deleterious effects of hydroxytyrosol supplementation on constriction of the ductus arteriosus, a possible secondary effect of polyphenols during pregnancy, were found.

Characterization of Ageing- and Diet-Related Swine Models of Sarcopenia and Sarcopenic Obesity.

Sarcopenia and sarcopenic obesity are currently considered major global threats for health and well-being. However, there is a lack of adequate preclinical models for their study. The present trial evaluated the suitability of aged swine by determining changes in adiposity, fatty acids composition, antioxidant status and lipid peroxidation, development of metabolic disturbances and structural changes in tissues and organs. Iberian sows with clinical evidence of aging-related sarcopenia were fed a standard diet fulfilling their maintenance requirements or an obesogenic diet for 100 days. Aging and sarcopenia were related to increased lipid accumulation and cellular dysfunction at both adipose tissue and non-adipose ectopic tissues (liver and pancreas). Obesity concomitant to sarcopenia aggravates the condition by increasing visceral adiposity and causing dyslipidemia, insulin resistance and lipotoxicity in non-adipose tissues. These results support that the Iberian swine model represents certain features of sarcopenia and sarcopenic obesity in humans, paving the way for future research on physiopathology of these conditions and possible therapeutic targets.

The effects of sildenafil citrate on feto-placental development and haemodynamics in a rabbit model of intrauterine growth restriction.

The present study evaluated the effectiveness of sildenafil citrate (SC) to improve placental and fetal growth in a diet-induced rabbit model of intrauterine growth restriction (IUGR). Pregnant rabbits were fed either ad libitum (Group C) or restricted to 50% of dietary requirements (Group R) or restricted and treated with SC (Group SC). The treatment with SC improved placental development by increasing vascularity and vessel hypertrophy in the decidua. The assessment of feto-placental haemodynamics showed higher resistance and pulsatility indices at the middle cerebral artery (MCA) in fetuses treated with SC when compared with Group R, which had increased systolic peak and time-averaged mean velocities at the MCA. Furthermore, fetuses in the SC group had significantly higher biparietal and thoracic diameters and longer crown-rump lengths than fetuses in Group R. Hence, the SC group had a reduced IUGR rate and a higher kit size at birth compared with Group R. In conclusion, SC may provide potential benefits in pregnancies with placental insufficiency and IUGR, partially counteracting the negative effects of food restriction on placental development and fetal growth. However, the present study also found evidence of a possible blood overflow in the brain that warrants further investigation.

Identification of factors affecting colostrum quality of dairy Lacaune ewes assessed with the Brix refractometer.

In this Research Communication we assessed factors affecting colostrum quality of dairy Lacaune ewes using the Brix-refractometer. Colostrum from 536 lambings from one commercial intensive dairy Lacaune farm were analysed for the following factors with potential influence in colostrum quality: (1) ewe parity (n = 84-132), (2) length of previous dry period (PDP) (n = 23-214), (3) age at first lambing (AFL) of primiparous ewes (n = 9-88), (4) lambing season (n = 192 or 344), and (5) year (2011-2013, n = 142-203). Parity significantly affected colostrum quality, with primiparous ewes showing the highest Brix refractometer values (22·6 ± 5·6%, P < 0·0001), though values were similar among multiparous ewes. PDP length also significantly affected colostrum quality: ewes with the shortest PDP showed the worst quality (16·8 ± 4·2%, P < 0·0001), with quality gradually rising with PDP length. Colostrum quality was significantly higher in 2011 (21·0 ± 5·2%) than in 2012 or 2013 (P < 0·0001); this likely reflects the several-fold greater proportion of animals with long PDP in 2011. In contrast, neither AFL nor lambing season significantly affected colostrum quality. These results suggest that parity and PDP length can substantially affect ovine colostrum quality of dairy ewes under intensive management conditions and they further show the usefulness of the Brix refractometer for providing a rough estimation of colostrum quality on-farm. However, further studies are needed to determine a validated cut-off Brix value for identifying good-quality colostra in ovine species.

Ontogeny of Sex-Related Differences in Foetal Developmental Features, Lipid Availability and Fatty Acid Composition.

Sex-related differences in lipid availability and fatty acid composition during swine foetal development were investigated. Plasma cholesterol and triglyceride concentrations in the mother were strongly related to the adequacy or inadequacy of foetal development and concomitant activation of protective growth in some organs (brain, heart, liver and spleen). Cholesterol and triglyceride availability was similar in male and female offspring, but female foetuses showed evidence of higher placental transfer of essential fatty acids and synthesis of non-essential fatty acids in muscle and liver. These sex-related differences affected primarily the neutral lipid fraction (triglycerides), which may lead to sex-related postnatal differences in energy partitioning. These results illustrate the strong influence of the maternal lipid profile on foetal development and homeorhesis, and they confirm and extend previous reports that female offspring show better adaptive responses to maternal malnutrition than male offspring. These findings may help guide dietary interventions to ensure adequate fatty acid availability for postnatal development.

Postnatal pituitary and follicular activation: a revisited hypothesis in a sheep model.

The importance of postnatal pituitary activation as regards female reproductive development is not yet understood. By taking advantage of the experimental model developed in a previous study, i.e. ewe lambs expressing markedly different ovarian phenotypes at 50 days of age, we designed this study to determine whether differences found in ovarian status during the early prepubertal period are due to different patterns of postnatal pituitary activation, and to assess whether these differences have long lasting effects on subsequent reproductive performance. Results showed that ewe lambs with high antral follicle count (AFC) at 50 days of age had significantly lower plasma FSH concentrations and higher anti-Mullerian hormone (AMH) concentrations during the first 9 weeks of age compared with low AFC ewe lambs (P<0.0001). With a longitudinal experiment we showed that a high AFC in the early prepubertal period is associated with consistently higher AMH concentrations and numbers of antral follicles up to the postpubertal period, and with higher pregnancy rates in the first breeding season. In addition, the effect of age in decreasing AMH concentrations was more marked in the low AFC group. Results of the present study demonstrate that ewe lambs undergo different patterns of postnatal pituitary activation. A high AFC at 50 days of age indicates an advanced phase of ovarian maturation, which was accompanied by constantly higher AMH concentrations up to the postpubertal period, a greater ovarian response to FSH stimulation and by higher pregnancy rates at first mating, as compared with the low AFC group.

Supramolecularly Regulated Ligands for Asymmetric Hydroformylations and Hydrogenations.

Herein we report the use of polyether binders as regulation agents (RAs) to enhance the enantioselectivity of rhodium-catalyzed transformations. For reactions of diverse substrates mediated by rhodium complexes of the α,ω-bisphosphite-polyether ligands 1-5,a-d, the enantiomeric excess (ee) of hydroformylations was increased by up to 82 % (substrate: vinyl benzoate, 96 % ee), and the ee value of hydrogenations was increased by up to 5 % (substrate: N-(1-(naphthalene-1-yl)vinyl)acetamide, 78 % ee). The ligand design enabled the regulation of enantioselectivity by generation of an array of catalysts that simultaneously preserve the advantages of a privileged structure in asymmetric catalysis and offer geometrically close catalytic sites. The highest enantioselectivities in the hydroformylation of vinyl acetate with ligand 4 b were achieved by using the Rb[B(3,5-(CF3)2 C6 H3)4] (RbBArF) as the RA. The enantioselective hydrogenation of the substrates 10 required the rhodium catalysts derived from bisphosphites 3 a or 4 a, either alone or in combination with different RAs (sodium, cesium, or (R,R)-bis(1-phenylethyl)ammonium salts). This design approach was supported by results from computational studies.

Asymmetric Hydroformylation of Heterocyclic Olefins Mediated by Supramolecularly Regulated Rhodium-Bisphosphite Complexes.

Rhodium complexes derived from conformationally transformable α,ω-bisphosphite ligands combined with a suitable alkali metal BArF salt as a regulation agent (RA) provide high regio- and enantioselectivities in the asymmetric hydroformylation (AHF) of three heterocyclic olefins. The outcome of the AHF could be exquisitely regulated by choosing the appropriate RA with an increase in the ee, the reversal of the regioselectivity, or the complete suppression of one byproduct.

Melatonin deprival modifies follicular and corpus luteal growth dynamics in a sheep model.

This study assessed the effect of melatonin deprival on ovarian status and function in sheep. Experimental procedures were carried out within two consecutive breeding seasons. Animals were divided into two groups: pinealectomised (n=6) and sham-operated (n=6). The completeness of the pineal gland removal was confirmed by the plasma concentration of melatonin. Ovarian status was monitored by ovarian ultrasonography for 1 year to study reproductive seasonality. Follicular and corpus luteal growth dynamics were assessed during an induced oestrous cycle. As the effects of melatonin on the ovary may also be mediated by its antioxidant properties, plasma Trolox equivalent antioxidant capacity (TEAC) was determined monthly for 1 year. Pinealectomy significantly extended the breeding season (310±24.7 vs 217.5±24.7 days in controls; P<0.05). Both pinealectomised and sham-operated ewes showed a well-defined wave-like pattern of follicle dynamics; however, melatonin deficiency caused fewer waves during the oestrous cycle (4.3±0.2 vs 5.2±0.2; P<0.05), because waves were 1 day longer when compared with the controls (7.2±0.3 vs 6.1±0.3; P<0.05). The mean area of the corpora lutea (105.4±5.9 vs 65.4±5.9 mm(2); P<0.05) and plasma progesterone levels (7.1±0.7 vs 4.9±0.6 ng/ml; P<0.05) were significantly higher in sham-operated ewes compared with pinealectomised ewes. In addition, TEAC values were significantly lower in pinealectomised ewes compared with control ones. These data suggest that melatonin, besides exerting its well-known role in the synchronisation of seasonal reproductive fluctuations, influences the growth pattern of the follicles and the steroidogenic capacity of the corpus luteum.

Predictive value of antral follicle count and anti-Müllerian hormone for follicle and oocyte developmental competence during the early prepubertal period in a sheep model.

Circulating anti-Müllerian hormone (AMH) and antral follicle count (AFC) are addressed as suitable markers of oocyte quantity and quality during adulthood. To investigate whether AFC and circulating AMH could predict follicle development and oocyte quality during the prepubertal period we used 40-day-old ewe lambs with high, intermediate and low AFC (≥30, 16-29 and≤15 follicles respectively). The analysis of the response to the exogenous FSH ovarian reserve test showed a positive correlation between AFC, AMH plasma levels, total follicle number and the number of large follicles (≥3mm) grown after exogenous FSH administration. The incorporation of abattoir-derived oocytes collected from ovaries with different AFC in an in vitro embryo production system showed that a high AFC can predict oocyte quality in prepubertal ovaries, reflecting an ovarian status suitable for follicular development. The histological quantification of the ovarian reserve evidenced that AFC was not predictive of differences in either the number of healthy follicles or the size of the primordial follicle pool in prepubertal ovaries. Further studies are needed to investigate the implication on the reproductive performance of the significant inter-individual differences found in the present study in AFC and circulating AMH in the early prepubertal period.

Fertility in a high-altitude environment is compromised by luteal dysfunction: the relative roles of hypoxia and oxidative stress.

BACKGROUND: At high altitudes, hypoxia, oxidative stress or both compromise sheep fertility. In the present work, we tested the relative effect of short- or long-term exposure to high altitude hypobaric hypoxia and oxidative stress on corpora luteal structure and function. METHODS: The growth dynamics of the corpora lutea during the estrous cycle were studied daily by ultrasonography in cycling sheep that were either native or naïve to high-altitude conditions and that were supplemented or not supplemented with antioxidant vitamins. Arterial and venous blood samples were simultaneously drawn for determination of gases and oxidative stress biomarkers and progesterone measurement. On day five after ovulation in the next cycle, the ovaries were removed for immunodetection of luteal HIF-1alpha and VEGF and IGF-I and to detect IGF-II gene expression. RESULTS: The results showed that both short- and long-term exposure to high-altitude conditions decreased luteal growth and IGF-I and IGF-II gene expression but increased HIF-1 alpha and VEGF immunoexpression. The level of plasma progesterone was also increased at a high altitude, although an association with increased corpus luteum vascularization was only found in sheep native to a high-altitude location. Administration of antioxidant vitamins resulted in a limited effect, which was restricted to decreased expression of oxidative stress biomarkers and luteal HIF-1alpha and VEGF immunoexpression. CONCLUSIONS: Exposure of the sheep to high-altitude hypobaric hypoxia for short or long time periods affects the development and function of the corpus luteum. Moreover, the observed association of oxidative stress with hypoxia and the absence of any significant effect of antioxidant vitamins on most anatomical and functional corpus luteum traits suggests that the effects of high altitude on this ovarian structure are mainly mediated by hypoxia. Thus, these findings may help explain the decrease in sheep fertility at a high altitude.

Phenotypic characterization by high-resolution three-dimensional magnetic resonance imaging evidences differential effects of embryo genotype on intrauterine growth retardation in NOS3-deficient mice.

The Nos3-knockout mouse, deficient for endothelial constitutive nitric oxide synthase (NOS3), is affected by a reduction in the number and weight of the embryos and constitutes a good model for some features of preeclampsia and intrauterine growth retardation (IUGR). Deficiencies in conceptus growth and survival may result from factors inherent in the embryo itself or from deficiencies in uterine function. In the current study, we aimed to determine the effects of embryonic genotype independently of maternal genotype, which can affect uterine environment. Therefore, by using magnetic resonance imaging (MRI), we characterized the phenotypes of NOS3-defective (Nos3(-/-); n = 6), normal wild-type (Nos3(+/+); n = 5), and heterozygous (Nos3(+/-); n = 16) mouse fetuses. All of them were littermates obtained by breeding heterozygous mice (Nos3(+/-)); therefore, the maternal genotype was the same for all the fetuses. At Day 13.5 (i.e., Theiler stage TS 21-22), females were anesthetized and scanned with three-dimensional MRI. Analysis of the different measurements of the embryos and the gestational annexes showed no significant differences between Nos3(+/+) and Nos3(+/-); however, there was a trend toward larger sizes in Nos3(+/+), and values in Nos3(-/-) were significantly smaller than in Nos3(+/+) and Nos3(+/-). The reduction in the crown-rump length of Nos3(-/-) reached 12% when compared to Nos3(+/+) (P < 0.05); the effect was higher for head measurements (16% for occipito-snout length and biparietal diameter, P < 0.05 for both) and trunk diameter (17%, P < 0.05). Overall, the maximum area of fetuses in longitudinal planes decreased 27% (P < 0.05) when comparing Nos3(-/-) to wild-type Nos3(+/+). Finally, Nos3(-/-) showed a reduction of 29% in the maximum thickness of the placenta, which may be related to the appearance of IUGR due to compromised nutritional delivery to the fetus.

Developmental competence of antral follicles and their oocytes after gonadotrophin treatment of sows with gene polymorphisms for leptin and melanocortin receptors (Iberian pig).

PURPOSE: To evaluate possible differences in follicle and oocyte developmental competence after gonadotrophin treatment in sows of obese and lean genotypes. METHODS: Follicle dynamics, ovulation rate and oocyte developmental competence to embryo were compared between females, of obese (n = 7) and lean genotypes (n = 10), treated with 1,250 I.U. of eCG and 500 I.U. of hCG. RESULTS: The obese genotype showed lower numbers of follicles growing to preovulatory stages (12.4 ± 1.8 vs 18.6 ± 1.0, P < 0.05), of corpora lutea (16.0 ± 0.9 vs 23.5 ± 0.9, P < 0.05), and of recovered oocytes/embryos (8.0 ± 1.3 vs 12.9 ± 0.9, P < 0.05). Thereafter, embryo viability rates also decreased when compared to lean genotypes (62.5 vs 77.6%, P < 0.05). DISCUSSION: To our knowledge, this is the first study analyzing the effect of obese genotypes on the ovarian response to exogenous gonadotrophins in a non-rodent animal model, the pig. A lower efficiency of gonadotrophin treatments for stimulation of follicle development and induction of ovulation was observed.

Effects of L-Glutamine Supplementation during the Gestation of Gilts and Sows on the Offspring Development in a Traditional Swine Breed.

The use of amino acids during pregnancy, such as glutamine (Gln), seems to be a promising strategy in selected swine breeds to improve the offspring prenatal development. The main goal of the current study was to assess the development of the offspring from parity 1-3 sows of a traditional breed, which were supplemented with 1% glutamine after Day 35 of gestation, under farm conditions. A total of 486 (288 treated) piglets from 78 (46 treated) Iberian sows were used. At birth and slaughterhouse, fatty acid composition, metabolism, and mTOR pathway gene expression were analyzed. At birth, treated newborns showed greater amounts of specific amino acids in plasma, such as glutamine, asparagine, or alanine, and Σn-3 fatty acids in cellular membranes than control newborns. The expression of genes belonging to mTOR Complex 1 was also higher in treated piglets with normal birth-weight. However, these findings did not improve productive traits at birth or following periods in litters from supplemented gilts (parity 1) or sows (parities 2-3). Thus, further research is needed to properly understand the effects of prenatal glutamine supplementation, particularly in traditional swine breeds.

Differential Effects of Litter Size and Within-Litter Birthweight on Postnatal Traits of Fatty Pigs.

Fatty pigs are characterized by a thrifty genotype, adapted to harsh environments based on changes in metabolism and energy saving. Thus, we hypothesized that feto-maternal energy partitioning in large litters might have postnatal effects that might be independent of intrauterine growth restriction (IUGR) processes. Hence, the current work reported the influence of two effects on postnatal performance and carcass and meat quality of purebred Iberian pigs: (a) the effects of the number of piglets in the litter (high vs. low litter size), and (b) the effects of birthweight (low (LBW) vs. normal (NBW)) in large litters. The results confirmed that NBW piglets born in large litters had differences in developmental patterns of weight, back-fat deposition, and fatty acid (FA) composition when compared to NBW piglets from small litters. These results were different from those found in LBW piglets when compared to their NBW counterparts, which showed an initial asymmetrical growth and altered muscle FA composition at slaughtering. The assessment of FA composition indicated better metabolic status in NBW piglets from large litters than in LBW piglets. These data support the concept that the prenatal environment, even when the individual may cope with it, inescapably affects postnatal life.

A Cross-Sectional Study of Obesity Effects on the Metabolomic Profile of a Leptin-Resistant Swine Model.

Identifying metabolite signatures associated with obesity and related diseases might represent a valuable preventive and therapeutic tool to predict subjects at risk, establish an accurate prognosis, and monitor treatment success. The current cross-sectional study is aimed to evaluate the metabolite profile of diet-induced obesity in a porcine model of leptin resistance. Six Iberian female pigs prone to develop obesity (OB) were ad libitum fed a fat-enriched diet (HFD) for 82 days. Five lean Iberian sows (CON) in a maintenance diet served as controls. At the end of the dietary treatments, all animals were sacrificed, and plasma, liver, and muscle samples were immediately collected for nuclear magnetic resonance analysis. In plasma, signals corresponding to betaine, glycerophosphocholine/phosphocholine, glycine, and glutamate were decreased; and the valine signal was increased in OB sows compared to controls. Similarly, the betaine signal was decreased in the liver. No differences were detected in muscle. The observed metabolite changes suggest alterations in branched chain amino-acid metabolism and the methionine-homocysteine cycle, which have been previously associated with obesity-related diseases and type 2 diabetes in human observational studies. The current study supports the utilization of the leptin resistant Iberian pig for further interventional research in the field.

Maternal Metformin Treatment Improves Developmental and Metabolic Traits of IUGR Fetuses.

Metformin is an anti-hyperglycemic drug widely used for the treatment of insulin resistance and glucose intolerance and is currently considered for preventing large-for-gestational-age (LGA) offspring in pregnant women affected by obesity or diabetes. Our hypothesis was the opposite-metformin may be used for improving the development of offspring affected by intrauterine growth restriction (IUGR) and preventing the appearance of small-for-gestational-age (SGA) neonates in non-obese and non-diabetic but malnourished pregnancies. The current study, performed in a swine preclinical model of IUGR by undernutrition, showed that fetuses in the treated group showed no significant increases in body-weight, but showed a significantly higher weight of the brain, the total thoracic and abdominal viscera, the liver, the kidneys, the spleen, and the adrenal glands. Maternal metformin treatment was also related to significant increases in the fetal plasma concentration of parameters indicative of glycemic (glucose and fructosamine) and lipid profiles (triglycerides). Overall, these results suggest a protective effect of the treatment on the developmental competence of the fetuses. These findings may be of high value for human medicine in case of maternal malnutrition, since metformin is a cheap drug easily available, but also in case of placental deficiency, since metformin seems to improve placental development and function.

Polyphenols and IUGR Pregnancies: Effects of Maternal Hydroxytyrosol Supplementation on Hepatic Fat Accretion and Energy and Fatty Acids Profile of Fetal Tissues.

Maternal supplementation with hydroxytyrosol, a polyphenol present in olive leaves and fruits, is a highly promising strategy to improve the oxidative and metabolic status of fetuses at risk of intrauterine growth restriction, which may diminish the appearance of low-birth-weight neonates. The present study aimed to determine whether hydroxytyrosol, by preventing lipid peroxidation, may influence the fat accretion and energy homeostasis in the liver, as well as the fatty acid composition in the liver and muscle. The results indicate that hydroxytyrosol treatment significantly decreased the energy content of the fetal liver, without affecting fat accretion, and caused significant changes in the availability of fatty acids. There were significant increases in the amount of total polyunsaturated fatty acids, omega-3 and omega-6, which are highly important for adequate fetal tissue development. However, there were increases in the omega-6/omega-3 ratio and the desaturation index, which make further studies necessary to determine possible effects on the pro/anti-inflammatory status of the fetuses.

Maternal Metabolic Demands Caused by Pregnancy and Lactation: Association with Productivity and Offspring Phenotype in High-Yielding Dairy Ewes.

Pregnancy and lactation, especially when concurrent, create a rather metabolically demanding situation in dairy ruminants, but little is known about their effects on offspring phenotype and milk yield. Here, we evaluated the impact of pregnancy and lactation on the metabolic traits and productive performance of Lacaune dairy sheep and their offspring. Productive performance was measured in terms of milk yield, body weight (BW), body condition score (BCS), and size. Productivity was assessed during mid-pregnancy (75 ± 5 d) and late pregnancy (142 ± 4 d) and at 52 ± 5 d in the postpartum period. During pregnancy, high-yielding ewes had higher BW, BCS, plasma glucose, cholesterol, ß-OHB, and NEFA than low-yielding ewes, but lower levels of lactate and urea. High-yielding animals had lower BCS after lambing, but their lambs showed greater growth. Productivity during lactation was affected by ewe age and parity: Mature ewes (but not maiden sheep) whose BCS increased steeply during pregnancy yielded more milk in the subsequent lactation than those whose BCS did not increase. Lamb BW and size were positively associated with milk yield in the subsequent lactation. Mature ewes had higher yields than maiden sheep, and mature ewes with multiple pregnancies produced more milk than those with singleton pregnancies. Ewes with male singleton pregnancies also showed higher yield than those with female singletons. These results demonstrate that high-yielding dairy sheep, when appropriately fed and managed, can adequately cover the metabolic demands of pregnancy and high milk production (even when concurrent) without losing productivity.