Maternal Nutrition Restriction Research Articles

Review article: Nutritional effects on fetal development during gestation in ruminants

Intrauterine growth retardation is a massive problem in animal production as it influencesthe body composition, carcass quality, and impairs health. This condition can lead to areduction in neonatal survival, growth, feed efficiency utilisation, and future production bythe animals. Pregnancy may negatively influence maternal nutritional status because ofincreased uteroplacental blood flow, nutrient mobilisation, and transfer of nutrients from thedam to the fetus. The critical factor for fetal survival and health is an adequate nutrient andoxygen supply to the dam during gestation. This ability is dependent on her nutritionalsupply, body size, body composition, and metabolism during pregnancy. The placenta is aunique organ of reproduction that helps in the exchange of nutrients, respiratory gases andexcretory waste between the mother and offspring. Maternal nutrition restriction inembryonic, placenta and fetal stages of pregnancy can result in metabolic compromise,cardiovascular, renal and adipose tissue dysfunction. The major effects of nutritionalchallenges on fetoplacental growth and development appear to occur when the placenta israpidly developing. Poor nutrition caused by inadequate, excess or imbalanced nutrientintake has been shown to adversely affect subsequent reproductive performance (delayedpuberty, luteal inadequacy, reduced follicular reserve, reduced ovulation, and conceptionrates). Proteins, carbohydrates, fats, minerals and vitamins are key components in animalfeeds that are required for a daily maintenance diet. Amino acids serve as building blocks forproteins and essential precursors for the synthesis of different physiologicalmolecules–hormones, neurotransmitters, nitric oxide, creatine, glutathione, carnitine, andpolyamines.

Machine learning classification models for fetal skeletal development performance prediction using maternal bone metabolic proteins in goats.

BackgroundIn developing countries, maternal undernutrition is the major intrauterine environmental factor contributing to fetal development and adverse pregnancy outcomes. Maternal nutrition restriction (MNR) in gestation has proven to impact overall growth, bone development, and proliferation and metabolism of mesenchymal stem cells in offspring. However, the efficient method for elucidation of fetal bone development performance through maternal bone metabolic biochemical markers remains elusive.MethodsWe adapted goats to elucidate fetal bone development state with maternal serum bone metabolic proteins under malnutrition conditions in mid- and late-gestation stages. We used the experimental data to create 72 datasets by mixing different input features such as one-hot encoding of experimental conditions, metabolic original data, experimental-centered features and experimental condition probabilities. Seven Machine Learning methods have been used to predict six fetal bone parameters (weight, length, and diameter of femur/humerus).ResultsThe results indicated that MNR influences fetal bone development (femur and humerus) and fetal bone metabolic protein levels (C-terminal telopeptides of collagen I, CTx, in middle-gestation and N-terminal telopeptides of collagen I, NTx, in late-gestation), and maternal bone metabolites (low bone alkaline phosphatase, BALP, in middle-gestation and high BALP in late-gestation). The results show the importance of experimental conditions (ECs) encoding by mixing the information with the serum metabolic data. The best classification models obtained for femur weight (Fw) and length (FI), and humerus weight (Hw) are Support Vector Machines classifiers with the leave-one-out cross-validation accuracy of 1. The rest of the accuracies are 0.98, 0.946 and 0.696 for the diameter of femur (Fd), diameter and length of humerus (Hd, Hl), respectively. With the feature importance analysis, the moving averages mixed ECs are generally more important for the majority of the models. The moving average of parathyroid hormone (PTH) within nutritional conditions (MA-PTH-experim) is important for Fd, Hd and Hl prediction models but its removal for enhancing the Fw, Fl and Hw model performance. Further, using one feature models, it is possible to obtain even more accurate models compared with the feature importance analysis models. In conclusion, the machine learning is an efficient method to confirm the important role of PTH and BALP mixed with nutritional conditions for fetal bone growth performance of goats. All the Python scripts including results and comments are available into an open repository at https://gitlab.com/muntisa/goat-bones-machine-learning.

Effects of nutrition restriction of fat- and lean-line broiler breeder hens during the laying period on offspring performance, blood biochemical parameters, and hormone levels

To evaluate the effects of maternal undernutrition on the performance, blood biochemical indexes, and hormone levels of broiler chicks, two broiler breeder lines (a fat line and lean line) were given either 100% or 75% of the daily feed intake recommended by the Chinese Ministry of Agriculture from 27 to 54 wk. All hens were fed the same basal corn-soybean diet. Fertile eggs were collected and hatched. All chicks were fed the same basal diet for 56 d. Then, chick performance, blood biochemical indexes, and hormone levels were measured. The results showed that there were interactions between maternal nutrition and line for some parameters, such as the kidney index, glucose, triglyceride, insulin, glucagon, leptin, and triiodothyronine (P < 0.05). Chicks of the fat line had a lower level of serum glucose, triglyceride, albumin, glutamic-pyruvic transaminase, insulin, and thyroxin than those of the lean line (P < 0.05), but the opposite trend was seen for birth weight, heart index, leptin, and triiodothyronine (P < 0.05). Maternal undernutrition decreased the birth weight and thymus index (day 28) of offspring (P < 0.05), but these effects disappeared by day 56. Maternal undernutrition decreased glucose (day 28), urea nitrogen (day 56), creatinine (day 56), glutamic-pyruvic transaminase (day 56), creatinine kinase (day 56), and leptin (day 56) levels in the offspring's serum (P < 0.05) but increased creatinine (day 28), total protein (day 28), glutamic-pyruvic transaminase (day 28), and glucagon (day 28) levels (P < 0.05). In conclusion, different lines have different metabolic processes. Maternal nutrition restriction during the laying period did have effects on the offspring, and the compensation by offspring reduced the effect of maternal nutrition restriction.

Influence of moderate maternal nutrition restriction on the fetal baboon metabolome at 0.5 and 0.9 gestation

Background and aimsModerately reduced maternal nutrient availability during pregnancy has adverse effects on the fetuses' growth and metabolism during and after pregnancy. The aim of this study was to explore effects of maternal nutrition restriction (MNR) on key metabolites of the fetal energy metabolism, particularly amino acids (AA), nonesterified fatty acids (NEFA), acylcarnitines and phospholipids. These effects may reflect mechanisms relating MNR to later adverse outcomes. Methods and resultsPlasma and liver samples of fetal baboons, whose mothers were fed ad libitum (CTR) or MNR (70% of CTR), were collected at 0.5 and 0.9 gestation (G – term 184 days). Metabolites were measured with liquid chromatography coupled to mass spectrometry. In both, CTR and MNR, fetal metabolic profiles changed markedly between 0.5G and 0.9G. Fetal liver glucose concentrations were strongly increased. Hepatic levels of NEFA, sphingomyelins, and alkyl-linked phospholipids increased while plasma NEFA and acyl-linked phospholipids levels decreased with progression of gestation.At 0.5G, MNR fetal plasma levels of short- and medium-chain acylcarnitines were elevated, but did no longer differ between groups at 0.9G. At 0.9G, plasma levels of methionine and threonine as well as hepatic threonine levels were lower in the MNR group. ConclusionSmall differences in the concentrations of plasma and liver metabolites between MNR and CTR fetuses reflect good adaptation to MNR. Fetal liver metabolic profiles changed markedly between the two gestation stages, reflecting enhanced liver glucose and lipid levels with advancing gestation. Decreased concentrations of AA suggest an up-regulation of gluconeogenesis in MNR.

Neonatal malnutrition programs the oxidant function of macrophages in response to Candida albicans

Experimental maternal nutrition restriction models are used to investigate short or long-term consequences of nutritional deficiency on puppies' growth. By assuming that the immune function is directly related to host's nutritional status, the current study aims to investigate the effects of neonatal malnutrition on oxidative stress and on the cell death of the alveolar macrophage after in vitro infection by Candida albicans. Wistar rats were suckled by mothers fed on diets containing 17% protein (Nourished group) or 8% protein (Malnourished group) in the current assay. Both groups received the standard diet used in the vivarium until adulthood, after weaning. The results showed that the offspring from mothers fed on low-protein diet presented lower body weight from 5 days of life on. Their low weight remained until adulthood when it was compared to that of rats in the nourished group. Superoxide and nitric oxide production was lower in malnourished animals and it was accompanied by low inducible nitric oxide synthase gene expression levels in systems in which the alveolar macrophages were challenged by immunogenic stimulus. No significant differences were observed in comparisons performed between the nourished and malnourished groups in any of the analyzed cell viability (apoptosis/necrosis) parameters. The fungal inoculum-stimulated system induced higher oxidative stress and cell death by necrosis. The current study demonstrated that dietary restriction during lactation alters the oxidant function of alveolar macrophages in puppies; It happens from the gene transcription step to the release of mediators, thus compromising the host's defenses against Candida albicans. It raises the possibility that Candida albicans may cease to be a commensal fungus to become a pathogen in offspring that have suffered nutritional deficiency during critical developmental periods, due to impaired immune responses.

Maternal nutrition restriction affects carbohydrate and lipid metabolism in adult rat offspring

Maternal food restriction in early development stages may program risks for adverse health outcomes in the adult offspring.We evaluated if the moderate caloric restriction (30%) in dams during gestation and/or lactation impairs the glucose and lipid metabolism of male adult offspring rats (16-week-old). No effect of maternal caloric restriction (CR) during gestation and lactation was observed in blood glucose and insulin levels and hepatic glycogen content of offspring. However, the area under the curve for the glucose tolerance test was greater (P= 0.044) in rats born to caloric restricted dams during gestation or lactation, that is suggestive of impaired glucose tolerance in these animals. Rats born to nutritional-restricted dams during gestation and lactation showed higher (P< 0.05)GLUT4 mRNA abundance in the epididymal adipose tissue than rats born to dams that were food-restricted only in the gestation. The CR during gestation and lactation resulted in slight but not significant reduction in the GLUT4 mRNA abundance (p=0.069) in the soleus muscle. The hepatic lipids content increased, whereas the adiposity index at 16 weeks of age decreased (P< 0.05) in rats born to dams that were nutritional-restricted during gestation and lactation. These data show that the moderate caloric restriction in gestation and lactation affects the glucose and lipid metabolism of the offspring, and may become it more susceptible to chronic diseases such as insulin resistance in later life. Research supported by FAPESP (2011/22011-9)

Association of imprinting status of IGF2 with the pathophysiology of intrauterine growth retardation in rats

Insulin like growth factor 2 (IGF2) is a crucial imprinting gene which prompting placenta development and fetal growth. It demonstrates parent-of-origin-specific allelic expression that is epigenetically regulated by differential methylation of IGF2/H19 DMR. We aim to explore if abnormal IGF2 imprinting status that regulated by altered DNA methylation of IGF2/H19 DMR affects IGF2 expression leading to the occurrence of IUGR. First we established an IUGR model of rat at two different stages(19-d gestational age and 1-day-old) by maternal nutrition restriction, and the rat tissues in the control group and the IUGR group were collected which were divided into four subgroups(N=6~8, each subgroup): Subgroup 1 and Subgroup 2 was the placenta and liver tissue of fetuses with 19-d gestational age, respectively, Subgroup 3 and Subgroup 4 was the liver tissue and skeletal muscle tissue in the posterior limbs of 1-day-old rats, respectively. Then the mRNA and protein levels of IGF2 were tested in the four subgroups of the two groups. In each subgroup, pyrosequencing was used to test the DNA methylation level of imprinting control region IGF2/H19 DMR. We observed that the expression levels of IGF2 in the Subgroup1, Subgroup 2, Subgroup 3 were decreased significantly compared with the control group, but there were no obvious differences in the Subgroup 4 of the two groups. The pyrosequencing showed no significant differences in methylation levels of the CpG dinucleotides in IGF2/H19 DMR between the two groups. What’s more, the methylation ratio didn't change versus age, and maintained the same from fetus till adult, and it also stayed the same among different tissue types except for placenta which had a lower methylation fraction than the other tissues. We concluded that the expression of IGF2 was down-regulated in the IUGR rats, which could play an important role in the pathogenesis of IUGR. However, the down regulation was not always the result of the aberrant imprinting status of the imprinting control region H19 DMR, as there wasn't a clear association between the two. IGF2 could be down regulated through other pathways, such as histone modification, or altered imprinting of another control region, to mediate the development of IUGR.

Poor nutrition during pregnancy and lactation negatively affects neurodevelopment of the offspring: evidence from a translational primate model

Studies of the effects of prenatal nutrition on neurodevelopment in humans are complicated because poor nutrition occurs in the context of psychosocial stressors and other risk factors associated with poor developmental outcomes. Under controlled experimental conditions, we tested an effect of prenatal nutrition on neurodevelopmental outcomes in the nonhuman primate. Juvenile offspring of 19 female baboons, whose diets were either restricted [maternal nutrition restriction (MNR)] or who were fed ad libitum (control), were administered the progressive ratio task from the Cambridge Neuropsychological Test Automated Battery. Activity, persistence, attention, and emotional arousal were coded from videotapes. These established, reliable methods were consistent with those used to assess individual differences in the behaviors of school-age children. MNR offspring (3 female and 4 male offspring) had significantly fewer responses and received fewer reinforcements on the progressive ratio task than did control offspring (8 female and 4 male offspring). MNR offspring showed a more variable activity level and less emotional arousal than did control offspring. Female MNR offspring showed more variable and lower levels of persistence and attention than did female control offspring. Thus, under controlled experimental conditions, data support a main effect of prenatal nutrition on highly translatable neurodevelopmental outcomes. Nutritional interventions during pregnancy have been successfully used to target neurodevelopmental problems, such as increasing folic acid intake during pregnancy to decrease the incidence of neural tube defects. Results from the current study can be used to support the testing of nutritional preventive interventions for the most-common childhood behavior problems.

Challenges of Linking Early-Life Conditions and Disease Susceptibility

Since David Barker first raised concerns about the impact of poor maternal nutrition and fetal growth restriction on the infant’s long-term health (1,2), the obesity epidemic has shifted attention to the long-term effects of maternal over-nutrition and hyperglycemia in pregnancy (rev. in 3). Currently, one in five women is obese at the start of pregnancy and 2–10% are diagnosed with gestational diabetes mellitus (4). With the new diagnostic criteria for gestational diabetes mellitus, this number is expected to rise to ∼18% of pregnant women worldwide (5,6). Despite these foreboding increases, we still have limited insight into the underlying mechanisms that link in utero conditions to later susceptibility for chronic disease. The inability to assess intrauterine exposures is one significant barrier to progress in this area. The discovery of a marker or profile that would more precisely measure fetal exposure to adverse conditions could ultimately help to identify infants at increased risk for age-related diseases and target preventative strategies specifically to at-risk individuals. In this edition of Diabetes , Bouchard et al. (7) tackle this problem in their investigation of placental changes in cytosine methylation associated with maternal glucose tolerance. At the same time, their work exemplifies some of the common challenges in epigenomic research. Bouchard et al. report on a cohort of 98 French Canadian women who were assessed during pregnancy for …

Postnatal Pancreatic Islet β Cell Function and Insulin Sensitivity at Different Stages of Lifetime in Rats Born with Intrauterine Growth Retardation

Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and insulin sensitivity, we established the IUGR model by maternal nutrition restriction during mid- to late-gestation. Glucose tolerance test and insulin tolerance test(ITT) in vivo and glucose stimulated insulin secretion(GSIS) test in vitro were performed at different stages in IUGR and normal groups. Body weight, pancreas weight and pancreas/body weight of IUGR rats were much lower than those in normal group before 3 weeks of age. While the growth of IUGR rats accelerated after 3 weeks, pancreas weight and pancreas/body weight remained lower till 15 weeks of age. In the newborns, the fasting glucose and insulin levels of IUGR rats were both lower than those of controls, whereas glucose levels at 120 and 180 min after glucose load were significantly higher in IUGR group. Between 3 and 15 weeks of age, both the fasting glucose and insulin levels were elevated and the glucose tolerance was impaired with time in IUGR rats. At age 15 weeks, the area under curve of insulin(AUCi) after glucose load in IUGR rats elevated markedly. Meanwhile, the stimulating index of islets in IUGR group during GSIS test at age 15 weeks was significantly lower than that of controls. ITT showed no significant difference in two groups before 7 weeks of age. However, in 15-week-old IUGR rats, there was a markedly blunted glycemic response to insulin load compared with normal group. These findings demonstrate that IUGR rats had both impaired pancreatic development and deteriorated glucose tolerance and insulin sensitivity, which would be the internal causes why they were prone to develop type 2 diabetes.

Study on pancreatic islet β-cell function and insulin sensitivity at different stages of lifetime in rats born with intrauterine growth retardation

The intrauterine growth retardation (IUGR) model was established by maternal nutrition restriction during mid- to late-gestation. IUGR rats had both impaired pancreatic development and islet β-cell dysfunction. As the animals grew, the rats gradually showed impaired glucose tolerance and decreased insulin sensitivity. Key words: Intrauterine growth retardation; Diabetes mellitus, type 2; Islet β-cell function; Insulin sensitivity

Developmental Plasticity of the Microscopic Placental Architecture in Relation to Litter Size Variation in the Common Marmoset Monkey ( Callithrix jacchus)

Fetal demand, shaped by factors such as number of fetuses, may alter placental regulation of exchange, even when maternal nutrition restriction is not overt. The marmoset is an interesting model in which to examine this aspect of placental function due to unique placentation that leads to multiple fetuses sharing a unified placental mass. We demonstrated previously that the triplet marmoset placenta exhibits significantly higher efficiency than does the twin placenta. Here, we test the hypothesis that this increased efficiency is due to increases in changes in the microscopic morphology of the placenta. Stereology was employed to analyze the microscopic architecture of placentas from twin and triplet pregnancies. Compartments of interest were the trabeculae, intertrabecular space, fetal capillaries, and the surface area of the maternal–fetal interface. Placentas from the two litters did not differ significantly in overall volume or individual volumetric compartments, but triplet placentas exhibited significant expansion of the trabecular surface area in comparison to twins ( p = 0.039). Further, the two groups differed in the isomorphy coefficient, with triplet placentas having a significantly higher coefficient ( p = 0.001) and potentially a more complex microscopic topography. Differences in the maternal–fetal interface may be due to developmental constraints on gross placental growth that occur earlier in gestation, such that the only option for maintaining sufficient access to maternal resources or signaling pathways late in gestation is via an expansion of the interface. Despite the significant increase in overall surface area, individual triplet fetuses are associated with much less surface area than are individual twins, suggestive of alterations in metabolic efficiency, perhaps via differential amino acid transport regulation.

The effects of pregnancy malnutrition on the development of insulin resistance in rat offspring

To investigate the effects of pregnancy malnutrition on the occurrence of insulin resistance (IR) in rat offspring during adult stage and to find out the relationship between TNF-alpha and IR; and to find out a reasonable early nutritional intervention measure for the prevention of IR, through giving different diets to offspring. An IUGR model was built by maternal nutrition restriction. 80 newborn IUGR female pups were randomly divided into 4 groups, the mother rats were given the following diet respectively for 3 weeks after delivery, pups were fed by mother milk: (1) The IUGR (intrauterine growth retardation) rat model was used and the animals were divided into: IUGR control group (group S/N) fed with normal diet, (2) IUGR high-caloric diet group (group A), (3) IUGR high-protein and high-caloric diet group (group B) and (4) IUGR high-protein isocaloric diet group (group C). Each group had 20 pups and another 20 normal female pups were fed with normal diet as the normal control group (group C/N). All pups were weaned at the 4th week of age and fed with normal diet till the end of the experiment. At the 12th week (adulthood) and 48th week (senility) of life, body weight and length, the fasting blood glucose, insulin concentration, TNF-alpha of adipose tissue and body weight were measured. Body mass index (BMI), ISI (insulin sensitive index), IRI (insulin resistant index) and HBCI (beta cell insulin excretion index) and their correlation to TNF-alpha were calculated. At 12th week and 48th week of life, the insulin sensitivity of IUGR model group was significantly lower than group C/N, although there was no significant difference of body weight between these two groups. TNF-alpha was negatively correlated with ISI, positively correlated with IRI and no relation to HBCI. Group A and B was fatter and developed more severe IR. There were no significant differences in ISI, IRI, HBCI and TNF-alpha between group C and group C/N. IUGR offspring of pregnancy malnutrition mother rats showed IR at the age of 12th week. TNF-alpha was closely related to the occurrence of IR in IUGR pups. IUGR pups fed with high caloric diet or high protein and caloric diet at the early postnatal period amplified the metabolic abnormality. The high protein isocaloric diet is effective early nutritional intervention measure for the prevention of occurrence of IR at adulthood.