Intrauterine Growth Restriction Piglets Research Articles

Leucine alters blood parameters and regulates hepatic protein synthesis via mammalian/mechanistic target of rapamycin activation in intrauterine growth-restricted piglets.

Neonatal piglets often suffer low birth weights and poor growth performance accompanied by the disruption of protein metabolism, when intrauterine growth restriction (IUGR) takes place during pregnancy, leading to a higher mortality and bigger economic loss than expected. Leucine has been proposed to function as a nutritional signal-regulating protein synthesis in numerous studies. The aim of this study was to determine the effect of dietary leucine supplementation on the blood parameters and hepatic protein metabolism in IUGR piglets. Weaned piglets were assigned to one of four treatments in a 2 × 2 factorial arrangement: 1) piglets fed a basal diet with normal birth weight, 2) piglets fed a basal diet plus 0.35% l-leucine with normal birth weight, 3) IUGR piglets fed a basal diet with low birth weight, and 4) IUGR piglets fed a basal diet plus 0.35% l-leucine with low birth weight. The results showed that IUGR decreased serum aspartate aminotransferase and alkaline phosphatase activities and increased serum cortisol and prostaglandin E2 levels at 35 d of age (P < 0.05), suggesting the occurrence of liver dysfunction and stress response. Leucine supplementation increased serum alkaline phosphatase activity and decreased serum cortisol levels at 35 d of age (P < 0.05). IUGR decreased the lysozyme activity and complement 3 level in serum (P < 0.05), which were prevented by dietary leucine supplementation. IUGR piglets showed increased hepatic DNA contents while showing a reduced RNA/DNA ratio (P < 0.05). Piglets supplied with leucine had decreased RNA/DNA ratio in the liver (P < 0.05). Leucine supplementation stimulated hepatic protein anabolism through upregulating protein synthesis-related genes expression and activating the phosphorylation of mammalian/mechanistic target of rapamycin (mTOR) (P < 0.05). Moreover, IUGR inhibited the mRNA expression of hepatic protein degradation-related genes, indicating a compensatory mechanism for the metabolic response. Dietary leucine supplementation attenuated the suppression of the protein catabolism induced by IUGR in the liver. These results demonstrate that dietary leucine supplementation could alter the blood parameters and alleviated the disrupted protein metabolism induced by IUGR via enhanced mTOR phosphorylation to promote protein synthesis in weaned piglets.

Associations between testicular development and fetal size in the pig

BackgroundImpaired reproductive performance is the largest contributing factor for the removal of boars from commercial systems. Intrauterine growth restricted piglets represent 25% of the total number of piglets born and have impaired reproductive performance. This study aimed to improve the understanding of temporal changes in testicular gene expression during testes development in fetuses of different size. The lightest and closest to mean litter weight (CTMLW) male Large White × Landrace littermates were collected at gestational days (GD) 45, 60 and 90 (n = 5–6 litters/GD).ResultsTestes weight and testes weight as a percentage of fetal weight were not associated with fetal size at GD60 or 90. Fetal plasma testosterone was not associated with fetal size at GD90. There was no association between fetal size and seminiferous tubule area and number, number of germ or Sertoli cells per tubule. The lightest fetuses tended to have wider seminiferous tubules compared to the CTMLW fetuses at GD90 (P = 0.077). The testicular expression of KI67 (P ≤ 0.01) and BAX:BCL2 ratio (P = 0.058) mRNAs decreased as gestation progressed. Greater SPP1 mRNA expression was observed at GD60 when compared with GD45 and 90 (P ≤ 0.05). Lower expression of DMRT1 and SPP1 (P < 0.01) mRNAs was observed in testes associated with the lightest fetuses compared to the CTMLW fetuses at GD90.ConclusionsThese findings provide novel insights into the expression profiles of genes associated with testicular development and function. Further, these data suggest that programming of reproductive potential in IUGR boars occurs late in gestation, providing a platform for further mechanistic investigation.

Brain lipidomics and neurodevelopmental outcomes in intrauterine growth restricted piglets fed dairy or vegetable fat diets

Breast milk has neurodevelopmental advantages compared to infant formula, especially in low-birth-weight infants, which may in part relate to the fat source. This study compared neurodevelopmental outcomes in three-day-old normal birth weight (NBW) and intrauterine growth restricted (IUGR) piglets fed a formula diet with either vegetable oil (VEG) or bovine milk fat sources (MILK) for three weeks in a 2 × 2 factorial design. Behavioural tests, lipidomics, MRI and RNA sequencing analyses of plasma and brain tissue were conducted. The absolute levels of 82% and 11% of lipid molecules were different between dietary groups in plasma and hippocampus, respectively. Of the lipid molecules with differential abundance in the hippocampus, the majority were upregulated in MILK versus VEG, and they mainly belonged to the group of glycerophospholipids. Lower absolute brain weights, absolute grey and white matter volumes and behaviour and motor function scores, and higher relative total brain weights were present in IUGR compared to NBW with minor influence of diet. Cognitive function and cerebellar gene expression profiles were similar for dietary and weight groups, and overall only minor interactive effects between diet and birth weight were observed. Overall, we show that the dietary fat source influences the plasma and to a lesser degree the hippocampal lipidome and is unable to improve on IUGR-induced brain structural and functional impairments.

L-Arginine Supplementation for Nulliparous Sows during the Last Third of Gestation.

Simple SummaryNutrition of gestating sows plays an important role in the uteroplacental efficiency, muscle development, birth weight and viability of the piglets. This is especially important for nulliparous sows, since the reproductive performance of nulliparous sows is lower compared to multiparous ones. Previous studies have shown that arginine enhances angiogenesis and placental growth, being beneficial to fetus growth. Because during its formation process skeletal muscle tissue compete for nutrients with other organs also in formation during the intrauterine development, the increase of nutrient flow by enhancing angiogenesis may benefit the skeletal muscle formation during the fetal stage. In this sense, arginine supplementation for sows seems to be a promising nutritional strategy to maximize myogenesis and muscle development of piglets. In the present study, piglets born from sows fed diet with 1.0% L-arginine (ARG) had greater mRNA expression of the gene encoding myoblast determination protein (MYOD) and myogenin (MYOG) compared to the piglets born from sows at the control group. The mRNA expression of IGF-2 gene tended to be greater in piglets born from ARG sows compared to those born from control sows. Despite differences in gene expression, no differences in the histomorphometric variables of skeletal muscle were observed between piglets from arginine-supplemented and control sows. In conclusion, supplementation of 1.0% L-arginine for nulliparous sows from 85 to 114 days of gestation increased mRNA expression of the myogenic regulatory factors MYOD and MYOG and IGF-2 in skeletal muscle of piglets.We evaluated the effects of L-arginine supplementation during the last third of gestation on molecular mechanisms related to skeletal muscle development of piglets and litter traits at birth. Twenty-three nulliparous sows averaging 205.37 ± 11.50 kg of body weight were randomly assigned to the following experimental treatments: control (CON), where pregnant sows were fed diets to meet their nutritional requirements; arginine (ARG), where sows where fed CON + 1.0% L-arginine. Skeletal muscle from piglets born from sows from ARG group had greater mRNA expression of MYOD (p = 0.043) and MYOG (p ≤ 0.01), and tended to present greater mRNA expression (p = 0.06) of IGF-2 gene compared to those born from CON sows. However, there were no differences (p > 0.05) in the histomorphometric variables of fetuses’ skeletal muscle. The total weight of born piglets, total weight of born alive piglets, piglet weight at birth, coefficient of variation of birth weight, and the incidence of intrauterine growth restriction (IUGR) piglets did not differ between groups. No stillborn piglets (p < 0.01) were verified in the ARG sows compared to CON group. The blood levels of estradiol (p = 0.035) and urea (p = 0.03) were higher in ARG sows compared to those from the CON group. In summary, our data show that arginine supplementation of nulliparous sows at late gestation enhance mRNA expression of key myogenic regulatory factors, which likely contribute to improve animal growth rates in later stages of development.

Inclusion of Soluble Fiber During Gestation Regulates Gut Microbiota, Improves Bile Acid Homeostasis, and Enhances the Reproductive Performance of Sows

Interaction between the dietary fiber and the gut microbes can regulate host bile acid metabolism. This study sought to explore the effects of guar gum combined with pregelatinized waxy maize starch (GCW) in a gestation diet on reproductive performance, gut microbiota composition, and bile acid homeostasis of sows. A total of 61 large white sows were randomly grouped into the control (n = 33) and 2% GCW (n = 28) groups during gestation. GCW diet increased birth-weight of piglets, and decreased the percentage of intrauterine growth restriction (IUGR) piglets. In addition, dietary GCW reduced gut microbial diversity and modulated gut microbial composition in sows on day 109 of gestation. The relative abundance of bile salt hydrolase (BSH) gene-encoding bacteria, Lactobacillus and Bacteroides decreased after GCW administration, whereas no significant difference was observed in the fecal level of total glycine-conjugated and taurine-conjugated bile acids between the two groups. Dietary GCW increased the relative abundance of Ruminococcaceae (one of few taxa comprising 7α-dehydroxylating bacteria), which was associated with elevated fecal deoxycholic acid (DCA) in the GCW group. GCW administration lowered the concentrations of plasma total bile acid (TBA) and 7α-hydroxy-4-cholesten-3-one (C4) (reflecting lower hepatic bile acid synthesis) at day 90 and day 109 of gestation compared with the control diet. Furthermore, the levels of plasma glycoursodeoxycholic acid (GUDCA), tauroursodeoxycholic acid (TUDCA) and glycohyocholic acid (GHCA) were lower in the GCW group compared with the control group. Spearman correlation analysis showed alterations in the composition of the gut microbiota by GCW treatment was associated with improved bile acid homeostasis and reproductive performance of sows. In conclusion, GCW-induced improves bile acid homeostasis during gestation which may enhance reproductive performance of sows.

511 Late-Breaking: Dietary Glycine Supplementation During Growing and Finishing Phases Increases Body Weight and Improves Meat Quality of Intrauterine Growth Restricted Pigs

Abstract Glycine is required for maximum growth and development for growing pigs. Traditional swine diets are deficient in glycine. This is concerning for intrauterine growth restricted (IUGR) pigs (20–25% of all pigs born) as they are born with low bodyweights and underdeveloped skeletomuscular systems. Therefore, IUGR piglets are culled at birth, as they are unlikely to survive and unable to reach market weight at the same rate as normal birthweight (NBW) littermates. Additionally, IUGR pigs are not fed to market weight due to undesirable carcass attributes at slaughter such as increased subcutaneous fat deposition and decreased overall desirable protein yield. This study was designed to test the hypothesis that providing dietary glycine supplementation in traditional corn- and-soybean meal-based diets would improve the growth rate of IUGR pigs between weaning (age 21d) and market weight (age 188d). Fourteen IUGR pigs (birthweight = 0.98±0.03 kg, mean ± SEM) and 20 NBW pigs (birthweight = 1.44±0.02 kg, mean ± SEM) were obtained at weaning and used for this study. Pigs from each birthweight group were randomly assigned to 1% glycine + 0.19% corn starch treatment group or 1.19% alanine group (isonitrogenous control). Data were analyzed by using 2-way ANOVA and Duncan multiple comparison test. At 188 d of age, glycine supplemented IUGR pigs were 4.4 kg heavier (P &amp;lt; 0.05) than control IUGR pigs, and had similar (P &amp;gt;0.05) body weights to those NBW counterparts. Feed intake did not differ among the treatment groups (P &amp;gt;0.05). Additionally, glycine supplementation improved markers of meat quality in IUGR pig carcasses compared to control IUGR carcasses, including decreased backfat thickness, increased loineye area, and increased overall muscle score (P &amp;lt; 0.05). Overall, results of this study show that dietary glycine supplementation to IUGR pigs post-weaning has positive effects on lean tissue gain and meat quality. (Supported by USDA-NIFA)

Identifying Risk Factors for Low Piglet Birth Weight, High Within-Litter Variation and Occurrence of Intrauterine Growth-Restricted Piglets in Hyperprolific Sows

Simple SummaryPiglet mortality is an ongoing concern for pig production worldwide. Piglets that have a low piglet birth weight (PBW), suffer from intrauterine growth restriction (IUGR) or are born from litters with a high within-litter variation in PBW (CVPBW) have an increased risk of dying before weaning. IUGR piglets, CVPBW and a low PBW might be connected by the same risk factors, and in order to optimize fetal development in the litter, these risk factors should be identified. Free-access stall feeding, floor feeding and electronic sow feeding systems are commonly used feeding systems for gestating sows in Denmark. These systems differ in several points, including in sow competition at feeding. The nutritional status of the sow is important for fetal development, and so the feeding method during gestation is also expected to affect such development. Of the risk factors identified in this study, increasing litter size was considered the most critical. Only small differences were found between the feeding systems and these differed amongst groups. The results should inspire further investigation of those risk factors to clarify causes of the observed effects and what drives individual herd differences.This study aimed to identify risk factors affecting PBW, high CVPBW and the occurrence of IUGR piglets in 12 commercial Danish herds with hyperprolific sows using free-access stalls, floor or electronic sow feeding systems in the gestation unit. The following factors were investigated: the duration of previous lactation, the length of the interval from weaning to insemination, the length of gestation, litter size, parity, sow backfat thickness in late gestation and the type of feeding system in the gestation unit. The study included newborn piglets from 452 litters with the following production indicator averages: 21.3 piglets/L, 1235 g PBW, 22.9% CVPBW and 10.9% and 11.8% within-litter occurrence of severe and mild IUGR piglets, respectively. Increasing length of weaning-to-insemination interval decreased PBW by 25.8 g/day. For 2nd to 9th parity sows, each additional piglet in the litter increased CVPBW by 0.38%, the occurrence of severe IUGR piglets by 0.68% and mild IUGR piglets by 0.50%. Sows of 5th parity and older had a 1.39% higher CVPBW and 49.1 g lighter piglets compared with sows of 2nd to 4th parity. PBW was lower in one ESF herd, suggesting complex interactions that need to be further elucidated. The main critical risk factor observed was litter size.

Effects of Bacillus subtilis on jejunal integrity, redox status, and microbial composition of intrauterine growth restriction suckling piglets

The present study used intrauterine growth restriction (IUGR) piglets as an animal model to determine the effect of Bacillus subtilis on intestinal integrity, antioxidant capacity, and microbiota in the jejunum of suckling piglets. In total, 8 normal birth weight (NBW) newborn piglets (1.62 ± 0.10 kg) and 16 newborn IUGR piglets (0.90 ± 0.08 kg) were selected and assigned to three groups. Piglets were orally gavaged with 10-mL sterile saline (NBW and IUGR groups), and IUGR piglets were orally gavaged with 10-mL/d bacterial fluid (B. subtilis diluted in sterile saline, gavage in the dose of 2 × 109 colony-forming units per kg of body weight; IBS group; n = 8). IUGR induced jejunal barrier dysfunction and redox status imbalance of piglets, and changed the abundances of bacteria in the jejunum. Treatment with B. subtilis increased (P < 0.05) the ratio of villus height to crypt depth (VH/CD) in the jejunum, decreased (P < 0.05) the plasma diamine oxidase (DAO) activity, and enhanced (P < 0.05) the gene expressions of zonula occludens-1 (ZO-1), occludin, and claudin-1 in the jejunum of IUGR piglets. Treatment with B. subtilis decreased (P < 0.05) the concentration of protein carbonyl (PC) and increased (P < 0.05) the activities of catalase (CAT) and total superoxide dismutase (T-SOD) in the jejunum of IUGR piglets. Treatment with B. subtilis also increased (P < 0.05) gene expressions of superoxide dismutase 1 (SOD1), CAT, and nuclear factor erythroid 2-related factor (Nrf2), as well as the protein expressions of heme oxygenase-1 (HO-1), SOD1, and Nrf2 in the jejunum of IUGR piglets. Treatment with B. subtilis also improved the abundances and the community structure of bacteria in the jejunum of IUGR piglets. These results suggested that IUGR damaged the jejunal barrier function and antioxidant capacity of suckling piglets, and altered the abundances of bacteria in the jejunum. Treatment with B. subtilis improved the intestinal integrity and antioxidant capacity while also improved the abundances and structure of bacteria in the jejunum of suckling piglets.

Prenatal Skeletal Muscle Transcriptome Analysis Reveals Novel MicroRNA-mRNA Networks Associated with Intrauterine Growth Restriction in Pigs

Intrauterine growth restriction (IUGR) occurs in 15–20% of pig neonates and poses huge economic losses to the pig industry. IUGR piglets have reduced skeletal muscle growth, which may persist after birth. Prenatal muscle growth is regulated by complex molecular pathways that are not well understood. MicroRNAs (miRNAs) have emerged as the main regulators of vital pathways and biological processes in the body. This study was designed to identify miRNA–mRNA networks regulating prenatal skeletal muscle development in pigs. We performed an integrative miRNA–mRNA transcriptomic analysis in longissimus dorsi muscle from IUGR fetuses and appropriate for gestational age (AGA) fetuses at 63 days post conception. Our data showed that 47 miRNAs and 3257 mRNAs were significantly upregulated, and six miRNAs and 477 mRNAs were significantly downregulated in IUGR compared to AGA fetuses. Moreover, 47 upregulated miRNAs were negatively correlated and can potentially target 326 downregulated genes, whereas six downregulated miRNAs were negatively correlated and can potentially target 1291 upregulated genes. These miRNA–mRNA networks showed enrichment in biological processes and pathways critical for fetal growth, development, and metabolism. The miRNA–mRNA networks identified in this study can potentially serve as indicators of prenatal fetal growth and development as well as postnatal carcass quality.

The Effect of Different Feeding Systems on Salivary Cortisol Levels during Gestation in Sows on Herd Level.

Simple SummaryPhysiological stress increases the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the secretion of cortisol, which might cross the placenta and affect foetal development. Stress in sows can be affected by management factors such as enrichment, different feed systems of the housing accommodation, and is reflected in the salivary cortisol concentration. It is unclear how stressed the sow must be before there is an impact on foetal growth, but higher levels of cortisol might affect the maturity of piglets at birth as well as their birth weight. Therefore, it could be beneficial to accommodate gestating sows in the least stressful manner, not only for piglet performance but also for sow welfare. Cortisol concentration in sows seems to be influenced by a combination of parity and feed systems, but its connection to those factors, as well as to foetal development, warrants further investigation.The aim of this study was to investigate herd cortisol levels as an indicator of stress during gestation in three different feeding systems. Twelve commercial Danish herds with 800 to 3050 sows were included, with either free-access feeding stall (Stall), floor feeding (Floor), or electronic sow feeding (ESF; n = 4 herds per system). Saliva samples were collected from 30 sows/herd in the gestation unit for cortisol analysis with an average of 67.2 gestation days for ESF, 72.4 days for Floor, and 68.6 days for Stall. Data on piglet birth weight (PBW) and the percentage of intrauterine growth restricted (IUGR) piglets from 452 litters (9652 piglets, 8677 liveborn) from all 12 herds were obtained on the saliva collection days. The cortisol levels in saliva increased throughout gestation (p < 0.01), and lower concentrations were observed among sows belonging to Stall (4.80 nmol/L), compared to Floor (7.03 nmol/L) and ESF (7.87 nmol/L), and that difference was significant as an independent effect in the case of ESF (p < 0.01). There was no difference between Floor and ESF or Stall and Floor (p > 0.05). An interaction was observed between parity and feeding system, with parities 4–5 in ESF herds having lower levels than other parities within the ESF system (p = 0.02).

Differences in Intestinal Barrier Development between Intrauterine Growth Restricted and Normal Birth Weight Piglets.

Simple SummaryAnimals with intrauterine growth restriction (IUGR) are defined as neonates born at term but with low birth weight and a characteristic shape of the head. A number of structural and functional modifications in the IUGR intestine affecting its digestive and absorptive function and impairing intestinal barrier function have been reported in the past. Far less is known about the immune system in the gut of IUGR pigs. Therefore, the aim of the present study was to evaluate the structures of the immune system of the gut mucosa in IUGR neonates. We found that the immune deficiency in the gut mucosa that results from restricted intrauterine development occurs at postnatal day (PD) 7, but it disappears thereafter within a week. However, all examined IUGR piglets had an increased number of intraepithelial leukocytes in the gut mucosa on PD 14. We have shown that the immune system of the gut of IUGR piglets is able to quickly compensate for the immunological deficiency postnatally and hardly shows any morphological disabilities in later life.Intrauterine growth restricted (IUGR) piglets are born at term but have low birth mass and a characteristic shape of the head. Impaired general condition, especially in intestinal function, leads to an increase in the occurrence of diarrhoea and high mortality in the first days of life. So far, the mechanical and immunological gut barrier functions in IUGR are poorly understood. The aim of this study was to microscopically evaluate the early postnatal changes in the gut mucosa occurring in IUGR piglets. Whole-tissue small intestine samples were collected from littermate pairs (IUGR and normal) on postnatal day (PD) 7, 14 and 180 and analysed by light microscopy. We found that in the IUGR piglets, the percentage of intraepithelial leukocytes was reduced in the duodenum on PD 7, but it increased in the proximal and middle jejunum both on PD 7 and PD 14, which suggested the development of an inflammatory process. The number of goblet cells was also reduced on PD 14. The average size of the Peyer’s patches in the distal jejunum and ileum showed significant reduction on PD 7 as compared to normal pigs; however, on PD 14, it returned to normal. On PD 180, we did not find any differences in the measured parameters between the IUGR and the normal pigs. In conclusion, we found that in one-week-old IUGR pig neonates, the gut barrier and the immune system structures display signs of retarded development but recover within the second postnatal week of life.

100 President Oral Presentation Pick: Prematurity Blunts Protein Synthesis in Skeletal Muscle of Neonatal Pigs Independently of Birth Weight

Abstract Postnatal growth failure reduces lean mass accretion and increases adiposity. Previously we showed that preterm birth impairs the feeding-induced stimulation of mechanistic target of rapamycin (mTOR), translation initiation, and protein synthesis in skeletal muscle of neonatal pigs. Considering that pig body weight can vary widely at birth, we wished to differentiate the effect of prematurity versus BW on these responses. Pigs delivered by caesarean section at preterm (103 d) or term (112 d) gestation were fed parenterally for 4 d. On day 4, all pigs were fasted for 4 h and were either fasted one additional hour or fed an elemental meal by oral gavage, yielding four treatment groups: preterm fasted, preterm fed, term fasted, and term fed. A flooding dose of L-[4-3H]Phe was injected into pigs 30 min after feeding (30 min before euthanasia). Preterm and term pigs were stratified according to birth weight such that preterm pigs with the highest birth weight were compared to term pigs with the lowest birth weight (n = 10–13 per group). Despite similar birth weight of pigs in these two subgroups, relative body weight gain of preterm pigs was 33% lower than term pigs (22.0 vs. 32.9 ± 1.6 g·kg-1·d-1, P &amp;lt; 0.001). Gastrocnemius protein synthesis increased after feeding in both preterm and term pigs, but the increase was 18% lower in preterm than in term pigs pigs (Table 1). Feeding-induced AKT phosphorylation and mTOR-dependent 4EBP1 and S6K1 phosphorylation mirrored the pattern in protein synthesis. These results suggest that prematurity (rather than low birth weight, which is frequently associated with preterm birth) perturbs mTOR activation and protein synthesis after feeding. However, it is unclear whether an inadequate response to feeding also underpins poor growth in intrauterine growth restricted piglets. Research was supported by NIH and USDA.

Catch-up growth in intrauterine growth-restricted piglets associated with the restore of pancreatic and intestinal functions via porcine glucagon-like peptide-2 microspheres

ABSTRACT Intrauterine growth restriction (IUGR) results in abnormal morphology and gastrointestinal function, such as reduced villi height and crypt depth, thinner mucosa and muscle layers, and reduced brush border enzyme activities, delayed gastric emptying, increased stress response. As a gastrointestinal growth factor, the manner by which the porcine glucagon-like peptide-2 (pGLP-2) microsphere administration restored the gastrointestinal function and growth performance of IUGR piglets was investigated. Fourteen newborn Duroc × (Yorkshire × Landrace) IUGR piglets (0.92 ± 0.113 kg) were assigned into the IUGR (negative control group) and pGLP-2 microsphere groups. The piglets in group pGLP-2 were intraperitoneally administered with 100 mg pGLP-2 microspheres on day 1 after birth. From days 15 to 26 of trial, the body weight of the pGLP-2 group was significantly higher than that of the control. IUGR piglets of group pGLP-2 showed a significantly increased pancreas weight, serum insulin content and activity of lipase and amylase. Injection of pGLP-2 microspheres restored the intestinal absorptive capacity by significantly increasing the mRNA expression of the sodium-glucose cotransporter 1 in the jejunum and the peptide transporter 1 in the jejunum. It also restored the redox balance by increasing the catalase mRNA expression and decreasing the heat shock protein 70 mRNA expression. In addition, this improvement was associated with the significant increase in gut diameter, length and weight. Therefore, it was concluded that the injection of pGLP-2 microspheres was a suitable therapeutic strategy for compensatory growth in low birth weight IUGR piglets.

Liver transcriptome profiling and functional analysis of intrauterine growth restriction (IUGR) piglets reveals a genetic correction and sexual-dimorphic gene expression during postnatal development

BackgroundIntrauterine growth restriction (IUGR) remains a major problem associated with swine production. Thus, understanding the physiological changes of postnatal IUGR piglets would aid in improving growth performance. Moreover, liver metabolism plays an important role in the growth and survival of neonatal piglets.ResultsBy profiling the transcriptome of liver samples on postnatal Days 1, 7, and 28, our study focused on characterizing the growth, function, and metabolism in the liver of IUGR neonatal piglets. Our study demonstrates that the livers of IUGR piglets were associated with a series of complications, including inflammatory stress and immune dysregulation; cytoskeleton and membrane structure disorganization; dysregulated transcription events; and abnormal glucocorticoid metabolism. In addition, the abnormal liver function index in the serum [alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total protein (TP)], coupled with hepatic pathological and ultrastructural morphological changes are indicative of liver damage and dysfunction in IUGR piglets. Moreover, these results reveal the sex-biased developmental dynamics between male and female IUGR piglets, and that male IUGR piglets may be more sensitive to disrupted metabolic homeostasis.ConclusionsThese observations provide a detailed reference for understanding the mechanisms and characterizations of IUGR liver functions, and suggest that the potential strategies for improving the survival and growth performance of IUGR offspring should consider the balance between postnatal catch-up growth and adverse metabolic consequences. In particular, sex-specific intervention strategies should be considered for both female and male IUGR piglets.

Associations between foetal size and ovarian development in the pig

It is estimated that intra-uterine growth restricted piglets represent 25 % of the total number of piglets born. Growth restricted female pigs have impaired reproductive performance postnatally. HHowever, when during gestation this phenotype arises is not known. With this study, the aim was to improve the understanding of foetal ovarian development in normal and small foetuses throughout gestation. Female Large White X Landrace foetuses were obtained at gestational day (GD) 45, 60 and 90 (n = 5–6 litters/GD). Histological analysis of GATA4 stained foetal ovaries at GD60 and 90 indicated there were fewer primary follicles (P ≤ 0.05) in the foetuses weighing the least compared to those with a weight similar to the mean for the litter (CTMLW) at GD90. Plasma oestradiol concentrations were less in the foetuses with lesser weights compared with greater weight foetuses at GD90 (P ≤ 0.05). The RNA was extracted from ovaries of the lesser weight and CTMLW foetuses at GD45, 60 and 90 and qPCR was performed to quantify relative abundance of 12 candidate mRNAs for which encoded proteins that modulate ovarian function and development. Gestational changes in relative abundances of CD31, PTGFR, SPP1 and VEGFA mRNA transcripts were observed. Relative abundance of KI67 (P = 0.066) and P53 (P ≤ 0.05) was less in ovaries of the lesser weight compared to CTMLW foetuses at GD60. There was a lesser relative abundance of PTGFR mRNA transcript in ovaries from the foetuses with lesser weight compared to CTMLW foetuses at GD45 and 60 (P ≤ 0.05). These findings indicate that postnatal differences in the reproductive potential of growth restricted females are programmed early in gestation. It is hoped that further investigation will improve the understanding of the relationship between prenatal reproductive development and postnatal reproductive performance.

The Stomach Capacity is Reduced in Intrauterine Growth Restricted Piglets Compared to Normal Piglets

Simple SummaryLarge litters have resulted in a higher percentage of piglets suffering from intrauterine growth restriction (IUGR). There is a higher mortality in this subset of piglets and a large number die because they do not receive enough nutrients for energy within the critical first 24 h after birth. One source of nutrients for energy could be supplementation with extra colostrum from previously milked sows. However, there is no knowledge on the stomach capacity of IUGR piglets, and therefore, of how much colostrum could potentially be supplemented. This is important information in order to recommend how much supplementary colostrum IUGR piglets need in order to survive.Selection for increased litter sizes have decreased the average birth weight of piglets and up to 30% of newborn piglets in Danish herds show signs of intrauterine growth restriction (IUGR). It has been reported that around 48% of liveborn piglets dying between birth and weaning have empty stomachs, and that IUGR piglets do not ingest the recommended amount of colostrum to survive. The aim of this study was to investigate how much colostrum could be administrated depending on whether they were IUGR compared to normal piglets. Seventy-two piglets within 24 h of farrowing were classified as either IUGR or normal based on their head morphology. Stomach weight, length and capacity were measured along with bodyweight (BW). The results displayed a decreased BW, empty stomach weight and capacity in IUGR piglets, as well as a decreased relative stomach capacity in IUGR compared with normal piglets. In conclusion, birth weight is not the only factor influencing stomach capacity, and IUGR piglets have a smaller stomach capacity compared with normal piglets. It is estimated that IUGR piglets have the capacity to be given a bolus of 25 mL per kg/BW, whereas a normal piglet have a higher capacity (30 mL per kg/BW).

Administration of Glucose at Litter Equalization as a Strategy to Increase Energy in Intrauterine Growth Restricted Piglets.

Simple SummaryHyper-prolific sows with large litters require extra management in order to reduce piglet mortality. One of the reasons is high piglet birth weight variability in these large litters where piglets can range from 300 g to 2.5 kg in the same litter. In this study the strategy of giving energy at litter equalization to the smallest piglets was investigated as this is when most farmers handle the piglets for the first time. The treatments consisted of a control, oral and injected supplementation. There were no differences between the treatments of the piglets suggesting that it is too late to intervene at litter equalization, and if extra management actions are to have an effect then they most likely have to be given already at birth. More research is needed on how to handle the small and underdeveloped piglets in order to reduce piglet mortality.Hyper-prolific sows give birth to large litters and up to 25% of piglets born have been subjected to intrauterine growth restriction (IUGR). The aim of this study was to test whether an oral administration of glucose impacts the survival rate and body weight gain of IUGR piglets at weaning. Different methods (injection versus oral administration of glucose 6 mL or 12 mL, respectively) were tested on IUGR piglets at litter equalization (i.e., when piglets are handled the first time at 5–20 h after birth). Injecting glucose generated the highest whole-blood glucose level + 3 h after treatment, however, after this no differences were observed. Of the 237 IUGR piglets studied, 98 piglets died or were removed from the nurse sow (41%). Rectal temperature at litter equalization (0 h) was related to the survival of the piglets with an average temperature of 37.1 ± 0.1 °C in surviving piglets and 36.6 ± 0.1 °C in piglets that died. In conclusion, providing these extra management actions at litter equalization is too late to help piglets that have a low rectal temperature and are low on energy. More research investigating different management methods to deal with IUGR piglets are needed as many of these underdeveloped piglets will not survive.

Transcriptome Differences Suggest Novel Mechanisms for Intrauterine Growth Restriction Mediated Dysfunction in Small Intestine of Neonatal Piglets.

Impaired intestinal function is frequently detected in newborns with intrauterine growth restriction (IUGR), whereas the mechanism between transcriptome profiles and small intestinal dysfunction is still unclear. Therefore, this study was conducted by using IUGR neonatal piglets to uncover the mechanism underlying intestinal dysfunction. Neonatal piglets with IUGR and normal birth weight (NBW) were sacrificed at birth. Transcriptomic sequencing was performed on jejunum samples and generated 18,997 and 17,531 genes in NBW and IUGR groups, respectively. A total of 10 differentially expressed genes (DEGs) were identified; of note, only seven were mapped to the genome reference database, with two up-regulated (HSF4 and NR1H4; heat shock transcription factor 4 and nuclear receptor subfamily 1 group H member 4, respectively) and five down-regulated (SLC35C1, BTNL3, BPI, NLRP6, and SLC5A8; Solute carrier family 35 member C1, butyrophilin like 3, bactericidal permeability increasing protein, NLR family pyrin domain containing 6, and solute carrier family 5 member 8, respectively). Combining an enrichment analysis and reverse transcriptase–quantitative polymerase chain reaction validation of DEGs, our results proved the lipid metabolism disorder, intestinal dysfunction, and inflammatory response in IUGR piglets. Here, IUGR piglets presented lower concentration of glucose and triglyceride and higher concentration of total cholesterol and low-density lipoprotein cholesterol in plasma, compared with NBW piglets. Histological analysis revealed decreased mucins and increased apoptosis in both jejunum and ileum for IUGR piglets. Collectively, we found that IUGR induced intestinal dysfunction by altering lipid metabolism, intestinal barrier, and inflammatory response in neonatal piglets at birth, which provides new insights into the prevention and treatment of IUGR that protects against metabolic disorders and inflammatory-related diseases.

Color of Colon Content of Normal and Intrauterine Growth-Restricted Weaned Piglets is Associated with Specific Microbial Taxa and Physiological Parameters.

Simple SummarySelection for hyperprolific sows has increased litter sizes but has also increased the number of small piglets per litter. A large percentage of these piglets have been exposed to intrauterine growth restriction (IUGR) during gestation, and this is accompanied by higher mortality and reduced growth in pig production. In humans, IUGR is associated with long-term health consequences such as cardiovascular disease, as well as metabolic diseases such as type 2 diabetes. It is therefore of interest to study the gut microbiota (GM) of IUGR compared to normal piglets, as a well-balanced GM is associated with improved health outcomes. Differences in feces color was associated with different metabolite signatures and specific GM signatures. Understanding these differences in the composition of the microbial community and its functional capacity during weaning is important for pig production, as the GM play important roles in pig health and growth performance. A well-balanced gut microbiome is associated with improved health outcomes, but to date, the GM of IUGR piglets have only been sparsely investigated. Here, we investigated GM composition, color of colon content, and blood parameters of 20 IUGR and 20 normal 24-day-old piglets. No significant differences were detected in colon microbiota composition between IUGR and the normal piglets with respect to alpha and beta diversity measures. The colon content of these piglets displayed three colors: brown, black, and yellow. Interestingly, the color of the colon content varied with microbial community composition, with significant differences in the relative abundance of taxa belonging to Fusobacteria and Treponema. Fusobacteria were most abundant in yellow fecal samples, with a mean relative abundance around 5.6%, whereas this was 0.51% within brown and 0.02% for the black fecal samples. Fusobacteria positively correlated with total blood protein, albumin, and triglycerides. Contrarily, Treponema was at 0.9% the most abundant in black fecal samples, while present at 0.1% of relative abundance in brown fecal samples and 0.01% in yellow samples, correlating positively with blood iron content. This study indicates that colon/fecal content color can be used as indicator for specific GM and metabolite signatures.

Intrauterine growth restriction in piglets alters blood cell counts and impairs cytokine responses in peripheral mononuclear cells 24 days post-partum

Large litter sizes have resulted in more piglets being exposed to intrauterine growth restriction (IUGR). Growth restriction during fetal life is linked with lower growth efficiency and increased susceptibility to infections in postnatal life and IUGR may associate with an altered innate immune system. We investigated the haematological, thromboelastography and plasma biochemical profiles of IUGR and normal piglets as well as cytokine responses in peripheral blood mononuclear cells stimulated with lipopolysaccharide (LPS) at 24 days of age. Piglets were classified at birth based on their head morphology as either IUGR or normal. The present study showed a modulation of the immune function of IUGR pigs, characterized by an increase in neutrophil percentage and fibrinogen levels but a decrease in CD4+ T-cells. A lower level of LPS-induced IL-1β production was evident in IUGR pigs, suggesting immunological hypo-responsiveness. Furthermore, higher levels of reticulocytes, MCV and MCH and lower levels of erythrocytes in IUGR pigs suggest altered bone marrow hematopoiesis. All together, the results suggest a moderate suppression of the immune response of IUGR piglets, which may have implications for resistance to pathogen challenges in the post-weaning period. Serum metabolites and blood clotting profile did not differ between IUGR and normal piglets.