Intrauterine Growth Retardation Group Research Articles

Maternal Hypermethylated Genes Contribute to Intrauterine Growth Retardation of Piglets in Rongchang Pigs.

The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.

First-Trimester Screening Tests and Perinatal Outcomes

Aim: Early diagnosis of trisomies occupies an important place in the working life of perinatologists and obstetricians. Early diagnosis of this condition is very important in raising a healthy generation. Early diagnosis informs decisions such as mental and physical preparation after birth or termination of pregnancy. Early detection of this risk is ensured by testing fetal nuchal translucency (NT), free human chorionic gonadotropin-β (free-βhCG) and pregnancy-related plasma protein-A (PAPP-A) levels at appropriate intervals. Also, with the help of these tests, perinatal risks such as chromosomal abnormalities, intrauterine growth retardation (IUGR) and preterm birth can be detected, and precautionary measures can be taken. In this study, we are trying to find out if it is possible to predict IUGR using these tests in the first trimester and evaluating the infants born here. Perhaps retrospective evaluation of these tests can be used to prevent poor pregnancy outcomes or, if necessary, to reduce the incidence of complications by delivering babies in more appropriate centers. Method: One of the hospitals included in this study is a training and research hospital and the other is a state hospital with active birth management, where the number of births is higher than the regional average. This study was conducted using data obtained by pediatrics and obstetrics by scanning the records of patients who had gone to their centers for postnatal care and the babies who were born. The population that served as the control group was reached in the same way. The period for the study was limited to two years. Results: 257 patients who had enrolled in centers for prenatal care over two years were included in the study. While 132 healthy pregnant women participated in the study as a control group, 125 pregnant women diagnosed with IUGR were included in the study. When the screening tests were compared in the first trimester, the mean PAPP-A level was higher in the control group than in the patient group (p=0.006). Free β-hCG was also higher in the control group (p=0.024). The result after performing the necessary statistical adjustments PAPP-A showed the statistical significance of its value in the analysis. However, the same tests did not show the same success in the IUGR group and were not statistically successful in predicting poor neonatal outcomes. Conclusion: In this study, the use of PAPP-A level in the first trimester has been shown to provide successful results in estimating IUGR that may occur later in pregnancy. However, no parameter has shown the same predictive success in predicting poor neonatal outcomes.

Assessment of vitamin status; A, E and D in Egyptian neonates with IUGR: a cross sectional study

BackgroundNeonates with intrauterine growth retardation (IUGR) may present with fatal complications and permanent serious consequences. Vitamin status may influence fetal development. In this study we assessed vitamin A, E and D concentrations in umbilical cord blood in newborns with IUGR.MethodsMaternal data were obtained. Neonatal assessment included; age of gestation calculated from last menstrual period, Ultrasound (U/S), new Ballard, Apgar scores and anthropometric measurements including; Head circumference, length and weight. WHO growth percentile curves were used. Vitamin A, E and D in cord blood samples were measured by high performance liquid chromatography (HPLC) and ELISA consecutively.ResultsA total of 86 full term newborns were enrolled in this study, 42 (48.8%) with IUGR with gestational age (33.59 ± 1.20) week by U/S and 44 (51.2%) appropriate for gestational age neonates with gestational age (38.70 ± 1.50). Ballard and Apgar scores (p < 0.05) and Z scores for weight, length and head circumference (p < 0.001) at birth were significantly lower in neonates with Intrauterine growth retardation (IUGR) than appropriate for gestational age (AGA) neonates. The levels of Vitamin A, E and D were significantly lower in the IUGR group than the AGA (p < 0.05) for all. Significant positive correlations of weight with vitamin A, and E cord blood levels were found (p < 0.05), while length was significantly positively correlated only with vitamin A (p < 0.05). Head circumference showed significant positive correlations with the three vitamins (p < 0.05) for all.ConclusionNeonates with IUGR had significantly lower levels of Vitamin A, E and D than AGA neonates. Significant positive correlations of weight with vitamin A, and E cord blood levels was detected, while neonatal length was associated only with vitamin A level. The present study highlights the significance of nutritional policies for inhibiting deficiency of these vitamins during pregnancy and childhood.

Implications for miR-339-5p regulation of trophoblast proliferation and migration in placentas associated with porcine intrauterine growth retardation using integrated transcriptome sequencing analysis

Placental dysfunction is considered as one of the main etiologies of fetal intrauterine growth retardation (IUGR). MicroRNAs (miRNAs) have been demonstrated to be a vital epigenetic modification involved in regulating the placental function and pregnancy outcomes in mammals. However, the mechanisms underlying placenta-specific miRNAs involved in the occurrence and development of pig IUGR remain unclear. In this work, we compared the placental morphologies of piglets with IUGR and normal birth weight (NBW) by using histomorphological analysis and performed a miRNA–mRNA integrative analysis of the gene expression profiles of IUGR and NBW placentas through RNA sequencing. We also investigated the role of differentially expressed ssc-miR-339-5p/GRIK3 through an in vitro experiment on porcine trophoblast cells (PTr2). IUGR piglets had significantly lower birth weight, placental weight, placental efficiency, and placental villus and capillary densities compared with the NBW piglets (P < 0.05). A total of 81 differentially expressed miRNAs and 726 differentially expressed genes in the placentas were screened out between the IUGR and NBW groups. The miRNA–mRNA interaction networks revealed the key core miRNA (ssc-miR-339-5p) and its corresponding target genes. Subsequently, we found that upregulation of ssc-miR-339-5p significantly inhibited the migration and proliferation of PTr2 cells (P < 0.05). The dual-luciferase reporter system showed that GRIK3 was the target gene of ssc-miR-339-5p, and the transcription level of GRIK3 may be negatively regulated by ssc-miR-339-5p. Additionally, overexpression of ssc-miR-339-5p significantly increased (P < 0.05) the mRNA expression levels of genes involved in the cytokine–cytokine receptor interaction pathway. These results indicate that ssc-miR-339-5p may affect the migration and proliferation of trophoblast cells by regulating the expression of GRIK3 and altering the placental inflammatory response, resulting in a suboptimal morphology and function of the placenta and the development of pig IUGR.

COMPARATIVE CHARACTERISTICS OF TONSILLAR LYMPHOID COMPONENT IN FETUSES WITH INTRAUTERINE GROWTH RETARDATION AND NORMAL BODY WEIGHT IN LATE PRENATAL PERIOD

The aim of this work is to identify the morphological and functional features of the lymphoid component of the tonsils in foetuses with intrauterine growth retardation (IUGR) in the late prenatal period. Material and Methods. The autopsy material of the study was tonsils from 10 full-term stillborn foetuses of average body weight (3.0-3.5 kg) (comparison group hereinafter CG) and 11 stillborn foetuses weighing 2.1-2.5 kg (hereinafter IUGR). The morphological material was stained by histological, histochemical methods, followed by morphometry on an Olympus BX-41 microscope with subsequent processing with Olympus DP-soft version 3.1 program. Immunohistochemical study was carried out using the direct Coons technique. The paraffin slices were treated with monoclonal antibodies (mAb) to Thy-1, CD3, CD4, CD5, CD8, CD19, CD22, HLA-Dr. The specimens were studied with the help of Carl Zeiss Axioskop 40 FL luminescent microscope and photographed with a CANON A520 digital camera. The light intensity was analyzed, determining the optical density of immunofluorescence of the immune cells using the original method. Results. Lymphoid follicles average diameter in IUGR group was 35.45±1.507 μm, which is significantly less than the value in CG group – 54.90±1.286 μm, (p ≤0.05). The relative volume of lymphoid tissue in the tonsils of the foetuses with IUGR was also significantly lower, amounting to 63.36±2.110% compared to 72.20±2.898% in CG group (p ≤0.05), the density of cellular elements in ×600 field of vision (IUGR group – 112.63±2.284, CG – 123.40±3.392; p ≤0.05). In IUGR group, the number of CD5 lymphocytes was significantly higher, amounting to 15.63±1.286 c.u. (in CG group, 12.30±1.159 c.u.) (p ≤0.05). The population of mature CD19 lymphocytes was significantly reduced in IUGR group (IUGR – 62.09±2.625 c.u., CG – 77.0±2.660 c.u.; p ≤0.05). The luminescence intensity of the areas, where CD3-mature T-lymphocytes were localized, was significantly reduced in IUGR group in comparison with the indicator of CG group (group CG – 55.70±1.828 c.u., IUGR – 51.72±1.190 c.u.; p ≤0.05). In IUGR group, CD4 population was significantly reduced – 33.72±2.101 c.u., vs. 45.80±1.813 c.u. in CG group (p ≤0.05), while CD8 population was enlarged (41.90±1.578 vs. 33.0±1.632 c.u. in CG group) (p ≤0.05). Conclusion. The results of the quantitative and qualitative assessment of the lymphoid component of the palatine tonsils of foetuses with IUGR revealed signs of hypoplasia and delayed maturation of both Tand B-lymphoid populations against the background of increased suppressor activity. Complete maturation may occur in the early stages of the postnatal development of the child, at the same time, an increase in the population of B-1 lymphocytes, as well as an increase in the suppressor activity of CD8, which has already been formed in utero, can later play the role of an important link in the morphogenesis of immunopathological reactions of various origins.

Dietary ferulic acid supplementation improves antioxidant capacity and lipid metabolism in liver of piglets with intrauterine growth retardation

Intrauterine growth retardation (IUGR) can result in early liver oxidative damage and abnormal lipid metabolism in neonatal piglets. Ferulic acid (FA), a phenolic compound widely found in plants, has many biological functions, such as anti-inflammation and anti-oxidation. Thus, we explored the effects of dietary FA supplementation on antioxidant capacity and lipid metabolism in newborn piglets with IUGR. In the study, 24 7-day-old piglets were divided into three groups: normal birth weight (NBW), IUGR, and IUGR + FA. The NBW and IUGR groups were fed formula milk as a basal diet, while the IUGR + FA group was fed a basal diet supplemented with 100 mg/kg FA. The trial lasted 21 days. The results showed that IUGR decreased absolute liver weight, increased transaminase activity, reduced antioxidant capacity, and disrupted lipid metabolism in piglets. Dietary FA supplementation enhanced absolute liver weight, reduced serum MDA level and ROS concentrations in serum and liver, markedly increased serum and liver GSH-PX and T-SOD activities, decreased serum HDL-C and LDL-C and liver NEFA, and increased TG content and HL activity in the liver. The mRNA expression related to the Nrf2-Keap1 signaling pathway and lipid metabolism in liver were affected by IUGR. Supplementing FA improved the antioxidant capacity of liver by down-regulating Keap1 and up-regulating the mRNA expression of SOD1 and CAT, and regulated lipid metabolism by increasing the mRNA expression level of Fasn, Pparα, LPL, and CD36. In conclusion, the study suggests that FA supplementation can improve antioxidant capacity and alleviate lipid metabolism disorders in IUGR piglets.

Effects of Equol Supplementation on Growth Performance, Redox Status, Intestinal Health and Skeletal Muscle Development of Weanling Piglets with Intrauterine Growth Retardation.

Animals with intrauterine growth retardation (IUGR) usually undergo injured postnatal growth and development during the early period after birth. Equol (Eq), an isoflavan produced by gut bacteria in response to daidzein intake, has various health benefits. Therefore, the objective of this study was to evaluate whether Eq supplementation can influence the growth performance, redox status, intestinal health and skeletal muscle development of weanling piglets with IUGR. A total of 10 normal-birth-weight (NBW) newborn female piglets and 20 newborn female piglets with IUGR were selected. After weaning at the age of 21 d, 10 NBW piglets and 10 IUGR piglets were allocated to the NBW group and IUGR group, respectively, and offered a basal diet. The other 10 IUGR piglets were allocated to the IUGR + Eq group and offered a basal diet with 50 mg of Eq per kg of diet. The whole trial lasted for 21 d. At the end of the feeding trial, all piglets were sacrificed for the collection of serum, intestinal tissues and skeletal muscles. Supplementation with Eq increased the average daily gain (ADG), average daily feed intake (ADFI), duodenal villus height to crypt depth ratio (V/C), jejunal villus height and V/C, but reduced the duodenal crypt depth in neonatal piglets with IUGR. Meanwhile, Eq supplementation elevated the activities of superoxide dismutase (SOD) and catalase (CAT) in the serum and duodenum and the activity of SOD in the jejunum, but lowered malondialdehyde (MDA) content in the serum, jejunum and ileum of piglets with IUGR. In addition, supplementation with Eq reduced diamine oxidase (DAO) activity and the levels of D-lactate and endotoxin in serum, and the tumor necrosis factor-α (TNF-α) level in jejunum and ileum, whereas the concentration of serum immunoglobulin G (IgG) and the mRNA levels of intestinal barrier-related markers in jejunum and ileum of IUGR piglets were increased. Furthermore, supplementation with Eq elevated the percentage of fast-fibers and was accompanied with higher mRNA expression of myosin heavy chain IIb (MyHC IIb) and lower mRNA levels in MyHC I in the longissimus thoracis (LT) muscle of IUGR piglets. In summary, Eq supplementation can promote antioxidant capacity, maintain intestinal health and facilitate skeletal muscle development, thus resulting in the higher growth performance of IUGR piglets.

Elabela levels in pregnancies with intrauterine growth retardation.

The aim of our study is to examine maternal serum Elabela levels in pregnancy with intrauterine growth retardation (IUGR). IUGR is one of the most important causes of perinatal mortality and morbidity. IUGR is also related future comorobidities such as diabetes mellitus, hyperlipidemia, hypertension and coronary artery disease. Fifty pregnancies diagnosed as IUGR (Group 1) and fifty healthy pregnancies (Group 2) enrolled into the study. Obstetric and demographic characteristics of the patients, serum elabela levels, ultrasound parameters, cord pH value and APGAR scores of the newborns were recorded. In the study, which was planned as a prospective case-control study, an independent t test was used for the evaluation of continuous data and the Mann Whitney U test was used for the statistical evaluation of ordinal data. p < 0.05 was considered significant. The mean gestational age of the cases at delivery was 36.35 ± 1.29 in Group 1 and 38.16 ± 0.94 weeks in Group 2 (p < 0.05). Mean serum Elabela levels were 15.05 ± 9.03 in Group 1 and 8.96 ± 4.33 ng/mL in Group 2 (p < 0.0001). Mean newborn weights were 2498.20 ± 465.92 in Group 1 and 3179.44 ± 387.99 gr. in Group 2 (p < 0.0001). Systolic and diastolic blood pressure measurements taken on the day of delivery were higher in Group 1, and diastolic blood pressure was 77.0 ± 9.53 in Group 1 and 72.60 ± 13.37 mmHg in Group 2 (p < 0.05). Bilateral uterine artery Pulsatile Index (PI) and umbilical artery PI value were significantly higher in Group 1 (p < 0.05), and middle cerebral artery PI and cerebroplacental ratio were significantly lower in Group 1 compared to Group 2 (p < 0.05). Although the cord pH value, 1st and 5th minute APGAR scores were lower in Group 1 compared to Group 2, no statistically significant difference was found (p > 0.05). In our study, it was found that serum Elabela levels increased significantly in pregnancies complicated by IUGR compared to the control group.

Dietary bile acid supplementation alters plasma biochemical and hormone indicators, intestinal digestive capacity, and microbiota of piglets with normal birth weight and intrauterine growth retardation.

Piglets with intrauterine growth retardation (IUGR) have poor small intestinal morphology and function, resulting in impaired digestion and absorption of nutrients and lower growth performance. Bile acids (BA) are important in regulating digestive enzyme activity, digestion and absorption of lipids, intestinal development, and protecting the liver. The present study aimed to investigate the effects of dietary BA supplementation on plasma biochemical and hormone indicators, intestinal morphology and function, and microbial community in piglets with normal birth weight (NBW) and IUGR. Weaned piglets (24 IUGR and 24 NBW) were allocated to four groups (12 piglets per group) and fed the following diets: (i) NBW group, NBW piglets fed a basal diet; (ii) NBW + BA group, NBW piglets fed a basal diet with 400 mg/kg BA; (iii) IUGR group, IUGR piglets fed a basal diet; and (iv) IUGR + BA group, IUGR piglets fed a basal diet with 400 mg/kg BA. The feeding trial lasted 28 days. The results showed that IUGR decreased the weight of the jejunum, whereas dietary BA supplementation decreased the jejunum weight and increased the length, weight, and index of ileum in NBW piglets (p < 0.05). In addition, IUGR increased (p < 0.05) the plasma choline esterase (CHE) and glucose levels of weaned piglets regardless of BA supplementation. Dietary BA supplementation increased the plasma albumin, triglyceride, and total protein concentrations while decreased plasma aspartate transaminase (AST), alanine aminotransferase (ALT), CHE, lactate dehydrogenase, and NH3 levels regardless of IUGR (p < 0.05). The IUGR increased trypsin level in the ileum, whereas dietary BA supplementation decreased jejunal trypsin and lipase and ileal lipase levels of weaned piglets regardless of IUGR (p < 0.05). Spearman's correlation analysis revealed the potential link between the intestinal microbial community and intestinal health-related indices of weaned piglets. These findings suggest that IUGR could decrease small intestinal morphology and function, whereas dietary BA supplementation could promote the ileum development of NBW piglets, protect the liver by reducing plasma ALT and AST levels, and increase the proportion of potentially beneficial bacteria in the small intestine of NBW and IUGR piglets, contributing to intestinal development and health of weaned piglets.

Zinc Oxide Nanoparticle Improves the Intestinal Function of Intrauterine Growth Retardation Finishing Pigs via Regulating Intestinal Morphology, Inflammation, Antioxidant Status and Autophagy.

This study was to investigate effects of zinc oxide nanoparticle (Nano-ZnO) on growth, immunity, intestinal morphology and function of intrauterine growth retardation (IUGR) finishing pigs. Six normal birth weight (NBW) and 12 IUGR male piglets were obtained and weaned at 21 d. NBW-weaned piglets fed basal diets (NBW group), IUGR-weaned piglets allocated to two groups fed basal diets (IUGR group) and basal diets further supplemented 600 mg Zn/kg from Nano-ZnO (IUGR+Zn group), respectively. All pigs were slaughtered at 163 d. Results showed: (1) IUGR pigs showed no difference in body weight at 77d and 163d (P > 0.05), while had increased villus height (VH) and villus surface area in jejunum (P < 0.05) and enhanced interleukin-6, TNF-α and NF-κB mRNA expression (P < 0.05) as compared to NBW group; Compared with IUGR group, dietary Nano-ZnO did not affect the body weight (P > 0.05), but increased VH to crypt depth ratio and IgA concentration (P < 0.05) and decreased TNF-α and NF-κB mRNA expression in jejunum (P < 0.05). (2) IUGR increased the number of swollen mitochondria and autolysosomes, and protein expressions of sequestosome-1 (P62) and microtubule-associated protein light chain 3 B/A (LC3B/A) in jejunum as compared to NBW group (P < 0.05); Compared with IUGR group, Nano-ZnO decreased the number of swollen mitochondria and autolysosomes, and P62 and LC3B/A protein expression (P < 0.05). (3) IUGR increased mucosal contents of malondialdehyde and protein carbonyl (PC) and Keap1 protein expression (P < 0.05) as compared to NBW group; Compared with IUGR group, dietary Nano-ZnO increased activities of total antioxidant capacity, catalase, glutathione peroxidase, and glutathione content (P < 0.05), and enhanced nuclear respiratory factor 2 (Nrf2), glutamate-cysteine ligase modifier subunit and glutathione peroxidase 1 mRNA expression, and increased total and nuclear Nrf2 protein expression (P < 0.05), and decreased malondialdehyde and PC content, and Keap1 protein expression (P < 0.05) in jejunum. Results suggested that IUGR pigs showed postnatal catch-up growth and improved intestinal morphology, and dietary Nano-ZnO may further improve intestinal morphology, reduce inflammation, decrease autophagy and alleviate oxidative stress via Nrf2/Keap1 pathway in jejunum of IUGR pigs.

Effects of ferulic acid on the growth performance, antioxidant capacity, and intestinal development of piglets with intrauterine growth retardation.

Neonates with intrauterine growth retardation (IUGR) are prone to suffer from delayed postnatal growth and development during the early stages of life. Ferulic acid (FA) is a phenolic compound that is abundantly present in fruits and vegetables and has various health benefits. Hence, we explored whether FA supplementation could favorably affect the growth performance, antioxidant capacity, and intestinal development of piglets with IUGR. In total, eight normal-birth-weight (NBW) piglets and 16 piglets with IUGR (age, 7 d) were assigned to be fed either basic formula milk (NBW and IUGR groups, respectively) or basic formula milk supplemented with 100 mg/kg FA (IUGR + FA group) for 21 d. At necropsy, the serum and intestinal tissues were collected. FA supplementation increased (P < 0.05) the feed conversion ratio and serum total superoxide dismutase and catalase activities in piglets with IUGR. Moreover, FA supplementation elevated (P < 0.05) the duodenal lactase and maltase activities, jejunal villus height and jejunal maltase activity but reduced (P < 0.05) the duodenal crypt depth and duodenal and jejunal cell apoptosis, cleaved cysteinyl aspartic acid protease-3 (caspase-3) content and cleaved caspase-9 content in piglets with IUGR. In summary, FA supplementation could elevate antioxidant capacity and facilitate intestinal development, thus resulting in increased feed efficiency in piglets with IUGR.

Correlation of Lipin gene expression with hepatic fat content in rats with intrauterine growth retardation

To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR). Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content. The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05). Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.

Early supplementation of folate and vitamin B12 improves insulin resistance in intrauterine growth retardation rats.

Insulin sensitivity is changed during the neonatal period in small for gestational age (SGA) infants. Yet, the interventional strategies are still limited. We aimed to investigate the effects of supplementation with high folate and vitamin B12 diets in the early postnatal period on the changes in insulin sensitivity in an intrauterine growth retardation (IUGR) rat model. IUGR rat model was established by both low-protein diet feeding and daily diet restriction. High folate and vitamin B12 diet was supplied in IUGR as nutritional interventional group (IUGR-I), otherwise, the non-intervened IUGR group (IUGR-NI). In this study, male rats were studied in order to avoid hormonal and gender influence. At 21, 60 and 120 days, fasting plasma glucose, insulin, triglyceride, cholesterol, and homocysteine levels were measured among the control, IUGR-I, and IUGR-NI groups. Pearson analysis was used to evaluate the correlation between homocysteine and fasting blood glucose, insulin, HOMA-IR, triglyceride, and cholesterol levels. We established IUGR rat model by both low protein and restricted diet feeding during pregnancy and the incidence of IUGR pups was 93.33%. There was no difference in fasting glucose, insulin, HOMA-IR, triglyceride and cholesterol levels between the control, the IUGR-NI and the IUGR-I group at day 21. At day 60, insulin, HOMA-IR and triglyceride levels in the IUGR-I group were remarkably lower than those in the IUGR-NI group, but still higher than those in the control group (F=38.34, P=0.02; F=49.48, P=0.02; F=17.93, P<0.001, respectively). At day 120, glucose, insulin, HOMA-IR and Hcy levels in the IUGR-I group were obviously lower than those in the IUGR-NI group, although still higher than those in the control group (F=21.60, P<0.001; F=164.46, P<0.001; F=75.15, P<0.001; F=35.46, P<0.001, respectively). There were no significant differences in triglyceride and cholesterol levels between the IUGR-I group and the control group at day 120. At 120-day, homocysteine in IUGR-I group was highly positively correlated with fasting glucose and HOMA-IR (r=0.863, P=0.006; r=0.725, P=0.042, respectively); Only homocysteine was positively correlated with fasting glucose in IUGR-NI group (r=0.721, P=0.044). Early supplementation of folate and vitamin B12 improved insulin resistance and lipid levels in IUGR rats to some extent, along with decreasing homocysteine levels, but not enough to completely repair glucose and lipid metabolism.

Maternal plasma Elabela levels in intrauterine growth restriction

Purpose: The aim of this study was to investigate the role of Elabela in the etiopathogenesis of intrauterine growth retardation (IUGR). &#x0D; Materials and Methods: The present prospective study included 43 healthy pregnant women and 46 pregnant women with IUGR. Maternal serum were collected from the control group and IUGR group at time of delivery. Elabela levels were analyzed in maternal serum through ELISA method.&#x0D; Results: Lower Elabela levels (IUGR: 1.09 (0.61-15.61) ng / mL and Control: 1.44 (0.37-31.33) ng / mL) were observed in IUGR patients compared to controls. Elabela levels were positively correlated with gestational week and neonatal weight. (r = 0.263, p = 0.013 and r = 0.259, respectively; p = 0.014).&#x0D; Conclusion: The present study serves as the first study revealing the role of the decrease in Elabela in maternal serum on the etiopathogenesis of IUGR. This suggests that Elabela could be a potential drug target in cases with IUGR.

Docosahexaenoic acid activates the Nrf2 signaling pathway to alleviate impairment of spleen cellular immunity in intrauterine growth restricted rat pups.

Intrauterine growth retardation (IUGR) impairs immune function in children. IUGR is associated with an imbalance of oxidative stress and abnormal apoptosis. Therefore, an IUGR rats model was established to determine the antioxidant capacity and apoptosis in newborn IUGR rats and explored whether these effects were regulated after Docosahexaenoic acid (DHA) supplementation to rat pups. First, eight normal-birth-weight (NBW) and eight IUGR neonatal rats (a 10% low-protein diet) were used to obtain the antioxidant capacity and apoptosis in IUGR rat pups. Then, 32 newborn rats were randomly assigned to the normal birth weight (NBW), DHA supplementation for NBW (ND), IUGR, and DHA supplementation for IUGR (ID) groups. Starting from the 7th day after birth, DHA was given to the experimental group and the same volume of distilled water was given to the control group for 21 days. (1) DHA improved the serum and spleen CD4/CD8 ratios and IL-4 and IFN-γ mRNA expression. (2) DHA decreased the level of MDA, but increased T-AOC in serum and spleen. (3) DHA increased the protein expression of Bcl-2 while decreased Bax. (4) DHA increased protein expression of the Nrf2 signaling pathway and the downstream antioxidant genes GSH-PX and CAT. DHA may alleviate the impairment of spleen cellular immunity in IUGR rat pups by inhibiting oxidative stress and apoptosis related to the activation of Nrf2 signaling pathway.

The effect of ultrasound-guided intraperitoneal injection of ulinastatin on lung development in intrauterine growth-restricted fetal rabbits

Objectives To investigate the effect and mechanism of ulinastatin (UTI) on development of lungs in fetal rabbits with intrauterine growth retardation (IUGR). Methods Twenty pregnant rabbits were equally divided into normal, IUGR, UTI, and LY groups. The normal group was only injected with saline and marked with tattoo ink. IUGR models were established by injecting N-nitro-L-arginine methyl ester in the rabbits of IUGR, UTI, and LY groups. The three groups were injected with saline, UTI, or UTI + LY294002 (PI3K inhibitor) respectively, and then marked with tattoo ink. After cesarean section, neonatal weights, and levels of dipalmitoyl phosphatidylcholine (DPPC), nitric oxide (NO), P-Akt, P-eNOS, and pulmonary surfactant-associated protein A (SP-A) were determined in tissues of the lungs. Radial alveoli count (RAC), pulmonary interstitial ratio, and ultrastructural changes in type II alveolar epithelial cells (AEC II) were also determined through light and electron microscopy. Results Compared with control, the IUGR group showed significantly decreased weight, RAC, lamellar bodies in AEC II, and levels of P-Akt, P-eNOS, DPPC, NO, and SP-A, and increased pulmonary interstitial ratio (p < .05). The UTI treatment did not affect the weight; however, all other parameters were opposite to those observed in the IUGR group (p < .05). Furthermore, these UTI-mediated changes were inhibited by LY294002. Conclusions Intraperitoneal UTI injection can promote the development of lungs and increase pulmonary surfactant production in IUGR fetal rabbits, potentially by activating PI3K/Akt/eNOS/NO signaling.

Placental pathology in intrauterine growth retardation

Several histopathological features are found more frequently in placentas from pregnancies complicated by foetal growth restriction (FGR), including villous infarction, maternal vascular changes and villous morphological alterations, although around one quarter of placentas associated with FGR lack any morphological abnormality on routine examination. So, our aim is to study various morphometric and morphological changes in placentae of small for gestational age babies. The correlation of various maternal parameters like height, age and parity with the foetal weight, placental weight, foeto-placental ratio (F/P) and placental coefficient (PC) and lastly to know whether each diseases process has any specific change in placentae.A prospective randomised control study was conducted from August 2016 to August 2018 in the Department of obstetrics and gynaecology JSS Hospital Mysore Karnataka. The total number of deliveries during this period were 3430. Out of which 397 babies were diagnosed of having Intrauterine growth retardation (IUGR) Total number of 150 cases were studied out of which 100 placenta were from IUGR group (study group) and the remaining 50 placenta from healthy full term pregnancies(Control group). The incidence of IUGR in our study was 11.6%. The commonest maternal cause for IUGR was anaemia 43%, followed by 18 % cases of preeclampsia and in 37% cases cause was Idiopathic. Maternal characters such as age, parity, and height were studied in relation to foetal outcome. An increase in the birth weight and placental weight was found with an increase in maternal age, height as well as parity. The mean placental weight in IUGR group was 484 grams while in control group was 520 grams. The average surface area in placentae in study group was 200.96 sq.cms. While in control group was 254 sqcms.

Dietary Supplemented Curcumin Improves Meat Quality and Antioxidant Status of Intrauterine Growth Retardation Growing Pigs via Nrf2 Signal Pathway.

Simple SummaryMore than 15% of piglets and about 10% of newborn humans suffer from intrauterine growth retardation (IUGR), which refers to growth lag, developmental restriction and impaired organs in the fetus. IUGR exhibits programming consequences and exerts permanent negative effects on postnatal growth and health. Dietary supplemented curcumin, as the main natural polyphenol isolated from the natural antioxidant (turmeric), might show possible effects on antioxidant capacity, and the meat quality of IUGR pigs. Therefore, in our present study, 12 normal birth weight (NBW) and 24 IUGR neonatal female piglets were selected and fed control diets supplemented 0 (NBW), 0 (IUGR) and 200 (IUGR + Cur) mg/kg curcumin from 26 to 115 days of age (n = 12). The growth performance, meat quality, redox status and its related Nrf2 pathway were determined to test the hypothesis that curcumin may play beneficial roles against IUGR-induced oxidative stress. This study suggested that curcumin could serve as a potential natural antioxidant in nutrition interventions of IUGR offspring to enhance the redox status and improve the meat quality of leg muscles. These results attained from IUGR pig models can also provide some useful theoretical references for IUGR offspring in humans.Intrauterine growth retardation (IUGR) exhibits programming consequences and may induce oxidative stress in growing animals and humans. This study was conducted to investigate the hypothesis that dietary curcumin may protect growing pigs from IUGR-induced oxidative stress via the Nrf2 pathway. Twelve normal birth weight (NBW) and 24 IUGR female piglets were selected and fed control diets supplemented 0 (NBW), 0 (IUGR) and 200 (IUGR + Cur) mg/kg curcumin from 26 to 115 days of age (n = 12). Growth performance, meat quality, redox status and its related Nrf2 pathway were determined. Results showed that IUGR pigs exhibited decreased body weight on 0 d, 26 d and 56 d (p < 0.01) but had no difference on 115 d among NBW, IUGR and IUGR + Cur groups (p > 0.05). Compared with NBW and IUGR groups, a significant decrease in drip loss (24 h and 48 h) was observed in the IUGR + Cur group (p < 0.01). IUGR pigs had higher concentrations of malondialdehyde (MDA) (p < 0.01) and protein carbonyl (PC) (p = 0.03) and lower activities of glutathione peroxidase (p = 0.02), catalase (p < 0.01) and peroxidase (p = 0.02) in leg muscles than NBW pigs. Dietary-added 200 mg/kg curcumin decreased concentrations of MDA and PC and improved the activities of catalase, superoxide dismutase (SOD) and peroxidase as compared to the IUGR group (p < 0.05). Additionally, dietary curcumin enhanced protein (NQO1) and mRNA expression of genes (Nrf2, NQO1, gamma-glutamyltransferase 1 (GGT1), heme oxygenase-1 (HO-1), glutathione S-transferase (GST) and catalase (CAT)) as compared to the IUGR group (p < 0.05). These results suggest that dietary curcumin could serve as a potential additive to enhance redox status and improve meat quality of IUGR growing pigs via the Nrf2 signal pathway.

Hypophosphatemia in Refeeding Syndrome in Intrauterine Growth Restricted IUGR Neonates Who are Receiving Nutrition: A Prospective Observational Study

Objective: Electrolyte dysregulations particularly hypophosphatemia and hypokalemia following feeds in a starved person is known as refeeding syndrome, which may lead to life-threatening conditions like arrhythmias, heart failure, respiratory and neuromuscular compromise. To evaluate electrolyte dyscrasias following enteral or parenteral feeding, among intrauterine growth retardation (IUGR) neonates ie those who were starved in-utero, compared to non-IUGR neonates this study was planned.&#x0D; Methodology: From March to August 2015, 60 IUGR and non-IUGR neonates who were admitted at birth before starting of nutrition, either by breast milk or electrolyte-free intravenous fluid. An infant was classified as IUGR when his birth weight was &lt;10th percentile according to Fenton or Lubchenco growth charts. Venous blood was collected from intramural babies at zero hours of life or just before starting feeds to determine the basal level of serum electrolytes – phosphorus, magnesium and potassium, and was repeated in the following 48 and 72 hours.&#x0D; Results: There was no significant difference between the two groups based on sex, history of maternal pre-eclampsia and oligohydramnios. At 72 hours after the start of feeding, Hypophosphatemia was significantly more prevalent, in 33.33% of IUGR vs. 2% of the non-IUGR group, [RR-5, p = 0.010]. Hypokalemia 20% IUGR; 1% non-IUGR group, [RR-6, p = 0.103]. Hypomagnesemia 3% IUGR; 2% non-IUGR group, [RR-1.5, p = 0.640]. Combined electrolyte– hypophosphatemia with hypokalemia (6.6%) and hypophosphatemia with Hypomagnesemia (13.3%), were present only in the IUGR group. Hyperglycemia was not present in any neonate. &#x0D; Conclusions: IUGR neonates are more likely to develop Refeeding syndrome when compared to non-IUGR babies, manifesting as decreased phosphorus, potassium and magnesium levels. Phosphorous should be a part of feeding nutrition in IUGR babies.

Effects of dietary dihydroartemisinin supplementation on growth performance, hepatic inflammation, and lipid metabolism in weaned piglets with intrauterine growth retardation.

The aims of this study were to investigate the effects of dietary supplementation with dihydroartemisinin (DHA) on growth performance, hepatic inflammation, and lipid metabolism in intrauterine growth retardation (IUGR)-affected weaned piglets. Eight piglets with normal birth weight (NBW) and 16 IUGR-affected piglets were selected and fed either a basal diet (NBW and IUGR groups) or the basal diet supplemented with 80mg/kg DHA (IUGR-DHA group) from 21 to 49 day of age. Blood and liver samples were collected on day 49. DHA supplementation significantly alleviated the compromised growth performance and liver damage in IUGR-affected piglets. Additionally, DHA supplementation decreased the activities of alanine aminotransferase and aspartate aminotransferase, as well as the serum levels of non-esterified fatty acids (NEFA), very-low-density lipoprotein, and total cholesterol. In the liver, the concentrations of interleukin 1 beta, interleukin 6, tumor necrosis factor alpha, triglycerides, and NEFA were decreased. Fatty acid synthesis was decreased by DHA supplementation, whereas the activities of lipoprotein lipase, hepatic lipase, and total lipase were increased. Dietary DHA supplementation led to upregulation of the expression of AMPK/SIRT1 signaling pathway-related genes, whereas that of inflammatory factor-related genes were downregulated. In conclusion, dietary inclusion of 80mg/kg DHA can alleviate IUGR-induced impairments in piglets.