Maternal Food Research Articles

Human Growth Hormone but Not Human Insulin-Like Growth Factor-I Enhances Recovery from Neonatal Malnutrition in Rats

The ability of hormonal therapy to enhance recovery from neonatal mainutrition was assessed in rats. Pups were mainourished via maternal food restriction (60% control intake). On d 16, restricted pups (n = 50) (62% control body wt) were refed until d 20 and were given growth hormone, insulin-like growth factor-I, destripeptide [1,3] insulin-like growth factor-I, or saline (placebo). Refed-placebo pups attained 80% of control body weight by d 20. Growth hormone treatment caused a greater weight gain than refeeding alone (P ≤ 0.05). Treatment with insulin-like growth factor-I and destripeptide [1,3] insulin-like growth factor-I did not affact body weight. All three hormones increased spleen and kidney weights (P ≤ 0.05) compared with the refedplacebo group, whereas only growth hormone increased muscle weight (P ≤0.05). Mainourished pups had lower serum insulin-like growth factor-I (P ≤ 0.05) and insulin-like growth factor binding protein-3 (P ≤ 0.05), and higher serum insulin-like growth factor binding protein-2 (P ≤ 0.05) and hepatic insulin-like growth factor binding protein-2 mRNA (P ≤ 0.05) than controls. Refeeding increased serum insulin-like growth factor-I compared with restricted pups (P ≤ 0.05), and insulin-like growth factor-I treatment caused a further increased in serum insulin-like growth factor-I compared with the refedplacebo group (P ≤ 0.05). These results show that growth hormone was moderately effective at increasing body weight gain and muscle growth during recovery from mainutrition.

Maternal Dietary Carbohydrate Restriction and Mild-to-Moderate Exercise during Pregnancy Modify Aspects of Fetal Development in Rats

To determine whether acute bouts of exercise during pregnancy would predispose the fetus to increased risk if maternal dietary carbohydrate were restricted, untrained pregnant rats were randomly assigned to a 0% (low), 12% (moderate) or 60% (high) glucose diet, and either rested or exercised daily for 20 min from d 16 to term on a rodent treadmill at a mild (15.5 m/min) or moderate (24.3 m/min) intensity. A 3 ՠ3 nested factorial model with and without food intake as a covariate was employed. Both greater exercise intensity and the lower levels of dietary carbohydrate independently decreased term maternal liver and plantaris glycogen concentrations and increased plasma lactate concentrations. However, significant differences due to exercise disappeared (except for plasma lactate) with food intake controlled for in the model, indicating that energy deficits modulated these exercise effects. In contrast, for the offspring, when food intake was controlled for, a restricted level of maternal dietary carbohydrate significantly lowered fetal weight, plasma glucose and insulin concentrations and liver glycogen concentrations measured at term. Exercise alone did not reduce mean fetal weight if nested weights within a litter were used in the statistical analysis. Mild to moderate maternal exercise lowered only fetal plasma glucose concentrations and only if maternal food intake was not controlled for. These results indicate that acute exercise during pregnancy can have detrimental effects on fetal development only if dietary glucose is severely restricted. Otherwise, adequate glucose and energy in the maternal diet in untrained pregnant rats during repeated bouts of acute exercise seem to protect the fetus.

Assessing Sensory Attributes and Properties of Infant Formula Milk Powder Driving Consumers’ Preference

Infant formula milk powder (IFMP) is an excellent substitute for breast milk. It is known that the composition of maternal food during pregnancy and lactation and exposure level to food during infancy highly influence taste development in early infancy. However, little is known about the sensory aspects of infant formula. Herein, the sensory characteristics of 14 brands of infant formula segment 1 marketed in China were evaluated, and differences in preferences for IFMPs were determined. Descriptive sensory analysis was performed by well-trained panelists to determine the sensory characteristics of evaluated IFMPs. The brands S1 and S3 had significantly lower astringency and fishy flavor compared to the other brands. Moreover, it was found that S6, S7 and S12 had lower milk flavor scores but higher butter scores. Furthermore, internal preference mapping revealed that the attributes fatty flavor, aftertaste, saltiness, astringency, fishy flavor and sourness negatively contributed to consumer preference in all three clusters. Considering that the majority of consumers prefer milk powders rich in aroma, sweet and steamed flavors, these attributes could be considered for enhancement by the food industry.

The association of maternal food quality score (FQS) with breast milk nutrient content and antioxidant content of infant urine: a cross-sectional study

BackgroundBreast milk (BM) is a complex fluid with a variable composition within women over time and between women in the population. The BM compositional differences are likely to be partly due to maternal dietary patterns. This study aimed to evaluate food quality score (FQS) in lactating mothers and its association with quality indicators of BM and antioxidant content of infant urine.MethodsThis cross-sectional study was undertaken in 350 lactating women aged 20 to 35 years. Data on dietary intake was collected using a validated food frequency questionnaire (FFQ) containing 65 food items. The FQS was calculated by integrating the scores obtained from healthy and unhealthy food groups. Subjects were categorized according to FQS adherence, with the greatest adherence being allocated to the third tertile and those with the lowest FQS in the first tertile. Antioxidant activity of the BM and infant urine samples was assessed using the Ferric reducing antioxidant power (FRAP), 2, 2′-diphenyl-1-picrylhydrazyl (DPPH), thiobarbituric acid reactive substances (TBARs), and Ellman’s assay. The total content of BM protein, calcium, and triglyceride was measured using standard biochemical kits.ResultsBM from mothers from the third tertile of FQS contained significantly higher DPPH, thiol, calcium, and protein levels compared to BM from those in the lowest tertile (p˂0.05). Infant urinary DPPH and FRAP was also significantly higher in the highest tertile vs. the lowest tertile (p˂0.05).ConclusionHigh maternal adherence to the FQS was associated with a high BM quality and antioxidant content of infant urine.

Multi-Omics Analysis Reveals the Potential Effects of Maternal Dietary Restriction on Fetal Muscle Growth and Development.

In terms of fetal muscle growth, development, and health, maternal nutrition is a crucial influence, although the exact biochemical mechanism by which this occurs is still not fully understood. To examine the potential impacts of maternal dietary restriction on fetal muscle development, the sheep maternal dietary restriction model was developed for this study. In our study, 12 pregnant ewes were evenly split into two experimental groups and fed either 75% or 100% of a maternal nutrient. In addition, a multi-omics analysis was used to study the embryonic longissimus dorsis on gestational days (GD) 85 and 135. The fetal weight at GD 135 was significantly below normal due to the maternal restricted diet (p < 0.01). When fetuses were exposed to the dietary deficit, 416 mRNAs and 40 proteins were significantly changed. At GD 85, the multi-omics analysis revealed that maternal dietary restriction led to a significant up-regulation of the cell cycle regulator CDK2 gene in the cellular senescence signaling pathway, and the results of the qRT-PCR were similar to the multi-omics analysis, which showed that SIX1, PAX7, the cell cycle factors CDK4 and CDK6, and the BCL-2 apoptosis factor were up-regulated and several skeletal muscle marker genes, such as MYF5 and MyoD were down-regulated. At GD 135, maternal dietary restriction blocks the muscle fiber differentiation and maturation. The multi-omics analysis revealed that the TEAD1 gene was in the Hippo signaling pathway, the muscle marker genes MYF5 and MyoG were significantly down-regulated, and the TEAD1 binding of the down-regulated VGLL3 gene might be potential mechanisms affecting myofiber differentiation and maturation. Knocking down the CDK2 gene could inhibit the proliferation of primary embryonic myoblasts, and the expression levels of cell cycle regulatory factors CDK4 and CDK6 were significantly changed. Under low nutrient culture conditions, the number of myoblasts decreased and the expression of CDK2, CDK6, MYF5, PAX7 and BCL-2 changed, which was in perfect agreement with the multi-omics analysis. All of the findings from our study helped to clarify the potential effects of maternal dietary restriction on fetal muscle growth and development. They also provided a molecular foundation for understanding the molecular regulatory mechanisms of maternal nutrition on fetal muscle growth and development, as well as for the development of new medications and the management of related metabolic diseases.

Placental nanoparticle gene therapy normalizes gene expression changes in the fetal liver associated with fetal growth restriction in a fetal sex-specific manner.

Fetal growth restriction (FGR) is associated with increased risk of developing non-communicable diseases. We have a placenta-specific nanoparticle gene therapy protocol that increases placental expression of human insulin-like growth factor 1 (hIGF1), for the treatment of FGR in utero. We aimed to characterize the effects of FGR on hepatic gluconeogenesis pathways during early stages of FGR establishment, and determine whether placental nanoparticle-mediated hIGF1 therapy treatmentcould resolve differences in the FGR fetus. Female Hartley guinea pigs (dams) were fed either a Control or Maternal Nutrient Restriction (MNR) diet using established protocols. At GD30-33, dams underwent ultrasound guided, transcutaneous, intraplacental injection of hIGF1 nanoparticle or PBS (sham) and were sacrificed 5 days post-injection. Fetal liver tissue was fixed and snap frozen for morphology and gene expression analysis. In female and male fetuses, liver weight as a percentage of body weight was reduced by MNR, and not changed with hIGF1 nanoparticle treatment. In female fetal livers, expression of hypoxia inducible factor 1 (Hif1α) and tumor necrosis factor (Tnfα) were increased in MNR compared to Control, but reduced in MNR + hIGF1 compared to MNR. In male fetal liver, MNR increased expression of Igf1 and decreased expression of Igf2 compared to Control. Igf1 and Igf2 expression was restored to Control levels in the MNR + hIGF1 group. This data provides further insight into the sex-specific mechanistic adaptations seen in FGR fetuses and demonstrates that disruption to fetal developmental mechanisms may be returned to normal by treatment of the placenta.

Maternal Diet Quality During Pregnancy and Offspring Hepatic Fat in Early Childhood: The Healthy Start Study

BackgroundOvernutrition in utero may increase offspring risk of nonalcoholic fatty liver disease (NAFLD), but the specific contribution of maternal diet quality during pregnancy to this association remains understudied in humans. ObjectivesThis study aimed to examine the associations of maternal diet quality during pregnancy with offspring hepatic fat in early childhood (median: 5 y old, range: 4–8 y old). MethodsData were from 278 mother–child pairs in the longitudinal, Colorado-based Healthy Start Study. Multiple 24-h recalls were collected from mothers during pregnancy on a monthly basis (median: 3 recalls, range: 1–8 recalls starting after enrollment), and used to estimate maternal usual nutrient intakes and dietary pattern scores [Healthy Eating Index-2010 (HEI-2010), Dietary Inflammatory Index (DII), and Relative Mediterranean Diet Score (rMED)]. Offspring hepatic fat was measured in early childhood by MRI. Associations of maternal dietary predictors during pregnancy with offspring log-transformed hepatic fat were assessed using linear regression models adjusted for offspring demographics, maternal/perinatal confounders, and maternal total energy intake. ResultsHigher maternal fiber intake and rMED scores during pregnancy were associated with lower offspring hepatic fat in early childhood in fully adjusted models [Back-transformed β (95% CI): 0.82 (0.72, 0.94) per 5 g/1000 kcal fiber; 0.93 (0.88, 0.99) per 1 SD for rMED]. In contrast, higher maternal total sugar and added sugar intakes, and DII scores were associated with higher offspring hepatic fat [Back-transformed β (95% CI): 1.18 (1.05, 1.32) per 5% kcal/d added sugar; 1.08 (0.99, 1.18) per 1 SD for DII]. Analyses of dietary pattern subcomponents also revealed that lower maternal intakes of green vegetables and legumes and higher intake of “empty calories” were associated with higher offspring hepatic fat in early childhood. ConclusionsPoorer maternal diet quality during pregnancy was associated with greater offspring susceptibility to hepatic fat in early childhood. Our findings provide insights into potential perinatal targets for the primordial prevention of pediatric NAFLD.

Decreased ubiquitin modifying enzyme A20 associated with hyper-responsiveness to ovalbumin challenge following intrauterine growth restriction

BackgroundIntrauterine growth restriction (IUGR) is strongly correlated with an increased risk of asthma later in life. Farm dust protects mice from developing house dust mite-induced asthma, and loss of ubiquitin modifying enzyme A20 in lung epithelium would abolish this protective effect. However, the mechanisms of A20 in the development of asthma following IUGR remains unknown.MethodsAn IUGR rat model induced by maternal nutrient restriction was used for investigating the role of A20 in the response characteristics of IUGR rats to ovalbumin (OVA) challenge. The ubiquitination of proteins and N6-methyladenosine (m6A) modifications were used to further assess the potential mechanism of A20.ResultsIUGR can reduce the expression of A20 protein in lung tissue of newborn rats and continue until 10 weeks after birth. OVA challenging can increase the expression of A20 protein in lung tissue of IUGR rats, but its level was still significantly lower than the control OVA group. The differentially ubiquitinated proteins in lung tissues were also observed in IUGR and normal newborn rats. Furthermore, this ubiquitination phenomenon continued from the newborn to adulthood. In the detected RNA methylations, m6A abundance of the motif GGACA was the highest. The higher abundances of m6A modification of A20 mRNA from IUGR were negatively correlated with the trend of A20 protein levels.ConclusionThese findings indicate A20 as a key regulator during the development of asthma following IUGR, providing further insight into the prevention of asthma induced by environmental factors.

Maternal lifestyle and nutrient intakes during pregnancy and exclusive breastfeeding in relation to risk factors for breast cancer: The Japan Environment and Children's Study

Breastfeeding has many benefits for infant growth and maternal health, such as reducing breast cancer risk. However, data on maternal factors influencing breastfeeding are insufficient. To clarify the associations between maternal lifestyle and diet during pregnancy and exclusive breastfeeding (EBF), we conducted a prospective study of pregnant women within the framework of the Japan Environment and Children's Study (a nationwide birth cohort study). Of 97,413 pregnant women recruited between January 2011 and March 2014, 27,775 with a singleton first live birth whose dietary data during pregnancy and lactation data were complete were eligible. Using logistic regression, we evaluated the associations between lifestyle factors including smoking and prepregnancy body mass index and intake of nutrients (macronutrients, isoflavones, and dietary fiber), some of which are known risk factors of breast cancer, and EBF for one month postpartum (initiation of EBF). To investigate the associations of these factors with EBF for 6 months (continuation of EBF), 9582 women who had successfully completed one-month EBF were further followed up. Smoking and prepregnancy obesity were inversely associated with the initiation and continuation of EBF. Intakes of protein, fat, isoflavone, and dietary fiber were positively associated (p trend = 0.0001 for dietary fiber), and carbohydrate intake was inversely associated with the initiation of EBF. Dietary fiber intake was also associated with the continuation of EBF (p trend = 0.048). These findings indicate that maternal lifestyles during pregnancy affect lactation performance. Lifestyle adjustments during pregnancy may have favorable effects on maternal and children's health through successful breastfeeding.

Maternal preconception circulating blood biomarker mixtures, child behavioural symptom scores and the potential mediating role of neonatal brain microstructure: the S-PRESTO cohort

Human brain development starts in the embryonic period. Maternal preconception nutrition and nutrient availability to the embryo may influence brain development at this critical period following conception and early cellular differentiation, thereby affecting offspring neurodevelopmental and behavioural disorder risk. However, studying this is challenging due to difficulties in characterizing preconception nutritional status and few studies have objective neurodevelopmental imaging measures in children. We investigated the associations of maternal preconception circulating blood nutrient-related biomarker mixtures (~15 weeks before conception) with child behavioural symptoms (Child Behaviour Checklist (CBCL), aged 3 years) within the Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) study. The CBCL preschool form evaluates child behaviours based on syndrome scales and Diagnostic and Statistical Manual of Mental Disorders (DSM) oriented scales. These scales consist of internalizing problems, externalizing problems, anxiety problems, pervasive developmental problems, oppositional defiant, etc. We applied data-driven clustering and a method for modelling mixtures (Bayesian kernel machine regression, BKMR) to account for complex, non-linear dependencies between 67 biomarkers. We used effect decomposition analyses to explore the potential mediating role of neonatal (week 1) brain microstructure, specifically orientation dispersion indices (ODI) of 49 cortical and subcortical grey matter regions. We found that higher levels of a nutrient cluster including thiamine, thiamine monophosphate (TMP), pyridoxal phosphate, pyridoxic acid, and pyridoxal were associated with a higher CBCL score for internalizing problems (posterior inclusion probability (PIP) = 0.768). Specifically, thiamine independently influenced CBCL (Conditional PIP = 0.775). Higher maternal preconception thiamine level was also associated with a lower right subthalamic nucleus ODI (P-value = 0.01) while a lower right subthalamic nucleus ODI was associated with higher CBCL scores for multiple domains (P-value < 0.05). One potential mechanism is the suboptimal metabolism of free thiamine to active vitamin B1, but additional follow-up and replication studies in other cohorts are needed.

Plasticity of maternal environment-dependent expression-QTLs of tomato seeds

Seeds are essential for plant reproduction, survival, and dispersal. Germination ability and successful establishment of young seedlings strongly depend on seed quality and on environmental factors such as nutrient availability. In tomato (Solanum lycopersicum) and many other species, seed quality and seedling establishment characteristics are determined by genetic variation, as well as the maternal environment in which the seeds develop and mature. The genetic contribution to variation in seed and seedling quality traits and environmental responsiveness can be estimated at transcriptome level in the dry seed by mapping genomic loci that affect gene expression (expression QTLs) in contrasting maternal environments. In this study, we applied RNA-sequencing to construct a linkage map and measure gene expression of seeds of a tomato recombinant inbred line (RIL) population derived from a cross between S. lycopersicum (cv. Moneymaker) and S. pimpinellifolium (G1.1554). The seeds matured on plants cultivated under different nutritional environments, i.e., on high phosphorus or low nitrogen. The obtained single-nucleotide polymorphisms (SNPs) were subsequently used to construct a genetic map. We show how the genetic landscape of plasticity in gene regulation in dry seeds is affected by the maternal nutrient environment. The combined information on natural genetic variation mediating (variation in) responsiveness to the environment may contribute to knowledge-based breeding programs aiming to develop crop cultivars that are resilient to stressful environments.

Prenatal Healthy Dietary Patterns Are Associated with Reduced Behavioral Problems of Preschool Children in China: A Latent Class Analysis.

The relation between maternal dietary patterns during pregnancy and offspring behavioral problems is less verified. Therefore, we have aimed to assess the relationship between them and have hypothesized that children of mothers with healthy dietary patterns during pregnancy have better behavior. The 1612 mother-child pairs of the China-Anhui Birth Cohort Study (C-ABCS) have been enrolled as the study population. The dietary behaviors of mothers during early and mid-pregnancy have been investigated using a semi-quantitative food frequency questionnaire. Preschool child behavioral problems have been assessed. Clusters of maternal food groups intakes have been identified using latent class analysis, and the association between maternal dietary patterns and child behavioral problems has been subsequently analyzed using logistic regression. Maternal age at inclusion is 26.56 ± 3.51 years. There has been a preponderance of boys (53.3%). Maternal food groups intakes have been classified into four groups: "High-consumed pattern (HCP)", "Southern dietary pattern (SDP)", "Northern dietary pattern (NDP)", and "Low-consumed pattern (LCP)". The offspring with maternal SDP and NDP have lower emotional symptoms compared to the offspring with maternal LCP in the first trimester (p < 0.05). It has been reported to lower conduct problems in children with maternal SDP than the children with maternal LCP in the second trimester (p < 0.05). In boys, we have detected associations between first-trimester SDP and lower emotional symptoms (p < 0.05) and between second-trimester SDP with decreased peer relationship problems (p < 0.05). In girls, total difficulty scores are lower with second-trimester SDP (p < 0.05). Maternal SDP in early and mid-pregnancy predicts reduced behavioral problems in preschool children, while maternal HCP and NDP during pregnancy may result in fewer developmental benefits.

Joint Effects of Prenatal Folic Acid Supplement with Prenatal Multivitamin and Iron Supplement on Obesity in Preschoolers Born SGA: Sex Specific Difference.

Prenatal maternal nutrient supplementation has been reported to be associated with offspring obesity, but the reports are inconsistent and have mainly ignored the differences between the total children population and children born small for gestational age (SGA). This study aimed to examine the joint effects of folic acid, iron, and multivitamin supplementation during pregnancy on the risk of obesity in preschoolers born SGA. A total of 8918 children aged 3-6.5 years born SGA were recruited from Longhua District in Shenzhen of China in 2021. Their mothers completed a structured questionnaire about the child's and parents' socio-demographic characteristics, maternal prepregnant obesity, and mothers' prenatal supplementation of folic acid, iron, and multivitamin. In addition, the children's current weight and height were measured by trained nurses. Logistic regression models were used to analyze the associations between prenatal supplementations and the current presence of childhood obesity. After controlling for potential confounders, the results of the logistic regression analysis showed that prenatal supplement of folic acid (OR = 0.72, 95% CI = 0.55~0.93) was associated with a lower likelihood of being an obese preschooler born SGA. In contrast, the ingestion of multivitamin or iron supplements during pregnancy did not seem to be related to the likelihood of childhood obesity in preschoolers born SGA. Moreover, cross-over analysis of prenatal folic acid and multivitamin obtained significant negative associations of prenatal folic acid supplement only (OR = 0.73, 95% CI = 0.55~0.97) and combination supplement of folic acid and multivitamin (OR = 0.67, 95% CI = 0.50~0.90) with obesity of preschoolers born SGA; while the cross-over analysis of prenatal folic acid and iron observed significant negative associations between obesity of preschoolers born SGA and a combination supplement of folic acid and iron (OR = 0.70, 95% CI = 0.52~0.96). Furthermore, the aforementioned significant associations were only found in girls and not in boys when the analyses were stratified by sex. Our findings suggest that the prenatal folic acid supplementation may decrease the risk of obesity in preschool girls born SGA, and that this effect may be modified by prenatal multivitamin or iron supplementation.

Maternal voluntary physical exercise in the adult rat: evidence of exercise-associated differences in maternal food intake, and in brain effects on the progeny

ABSTRACT Objectives: Maternal physical activity may impact behavioral and electrophysiological aspects of brain function, with short- and long-term effects on pre- and postnatal neurodevelopment of the offspring. This study evaluated in the rat the effects of maternal voluntary physical activity (MVPA) on food intake and weight gain in the dams, as well as anxiety-like behavior, short-term memory and the brain excitability-related phenomenon known as cortical spreading depression (CSD) on the mother-pup dyad. Methods: Female Wistar rats (n=33) were individually housed in cages containing a running wheel for a 30-days adaptation period before mating. Rats were classified as inactive (I); active (A) or very active (VA) according to the distance spontaneously travelled daily. During gestation, the dams continued to have access to the running wheel. Mothers and their respective pups (1 pup per mother) were evaluated in the open field test (OFT), object recognition test (ORT), elevated plus maze test (EPMT) and the CSD propagation features. Results: MVPA was directly associated with increased food intake and weight gain during gestation, and maternal anxiolytic-like behavioral responses in the OFT. Pups from VA mothers showed a high discrimination index for shape recognition memory (ORT) and decreased propagation velocities of CSD, when compared with the inactive group. Discussion: The data suggest that MVPA during the gestational period induces neuroplasticity and may modulate the brain functions in the mother-infant dyad in the rat.

Placental treatment with insulin-like growth factor 1 via nanoparticle differentially impacts vascular remodeling factors in guinea pig sub-placenta/decidua.

Clinically, fetal growth restriction (FGR) is only detectable in later gestation, despite pathophysiological establishment likely earlier in pregnancy. Additionally, there are no effective in utero treatment options for FGR. We have developed a nanoparticle to deliver human insulin-like 1 growth factor (hIGF-1) in a trophoblast-specific manner which results in increased expression of hIGF-1. IGF-1 signaling in the placenta regulates multiple developmental processes including trophoblast invasion and maternal vascular remodeling, both of which can be diminished in the FGR placenta. We aimed to determine the effects of short-term hIGF-1 nanoparticle treatment on sub-placenta/decidua trophoblast signaling mechanisms in FGR and under normal growth conditions. Using the guinea pig maternal nutrient restriction (MNR) model of FGR, ultrasound-guided, intra-placenta injections of hIGF-1 nanoparticle were performed at gestational day 30-33, and dams sacrificed 5days later. Sub-placenta/decidua tissue was separated from placenta for further analyses. Western blot was used to analyze protein expression of ERK/AKT/mTOR signaling proteins (phospho-Erk (pERK), phospho-Akt (pAKT), raptor, rictor and deptor). qPCR was used to analyze gene expression of vascular/remodeling factors [vascular endothelial growth factor (Vegf), placenta growth factor (Pgf), platelet-derived growth factor (Pdgf)) and tight junction/adhesion proteins (claudin 5 (Cldn5), p-glycoprotein (Abcb1), occludin (Ocln) and tight junction protein 1 (Zo1)]. MNR reduced expression of pERK, PdgfB and Cldn5, and increased expression of Ocln and Zo1 in the sub-placenta/decidua. In MNR + hIGF1 nanoparticle sub-placenta/decidua, expression of PdgfB, Ocln and Zo1 was normalized, whilst pAkt, VegfB, Vegf receptor 1 and PdgfB receptor were increased compared to MNR. In contrast, hIGF-1 nanoparticle treatment of normal placentas reduced expression of pERK, raptor and increased expression of the mTOR inhibitor deptor. This was associated with reduced expression of VegfA, Plgf, and PdgfB. Here we have shown that the impact of hIGF-1 nanoparticle treatment is dependent on pregnancy environment. Under MNR/FGR, hIGF-1 nanoparticle treatment triggers increased expression of growth factors and normalization of EMT factors. However, under normal conditions, the response of the placenta is to decrease AKT/mTOR signaling and growth factor expression to achieve homeostasis.

Timing of maternal nutrient restriction during mid- to late-gestation influences net umbilical uptake of glucose and amino acids in adolescent sheep.

Previous research demonstrated that maternal nutrient restriction during mid- to late-gestation influenced net umbilical uptakes of glucose and amino acids in sheep. However, it is unclear how the timing and duration of nutrient restriction during mid- to late-gestation influences net uterine, uteroplacental, and fetal flux of glucose and amino acids. On day 50 of gestation, 41 adolescent ewe lambs carrying singletons were randomly assigned to one of six dietary treatments: 1) 100% of nutrient requirements from days 50 to 90 of gestation (CON; n = 7); 2) 60% of nutrient requirements (RES; n = 7) from days 50 to 90 of gestation; 3) 100% of nutrient requirements from days 50 to 130 of gestation (CON-CON; n = 6); 4) 100% of nutrient requirements from days 50 to 90 of gestation and 60% of nutrient requirements from days 90 to 130 of gestation (CON-RES; n = 7); 5) 60% of nutrient requirements from days 50 to 90 of gestation and 100% of nutrient requirements from days 90 to 130 of gestation (RES-CON; n = 7); or 6) 60% of nutrient requirements from days 50 to 130 of gestation (RES-RES; n = 7). On day 90 (n = 14) and day 130 (n = 27), intraoperative procedures were performed to evaluate uteroplacental blood flows, collect blood samples, and then ewes were euthanized. Net uterine, uteroplacental, and umbilical fluxes of glucose and amino acids were calculated by multiplying blood flow by the arterial-venous concentration difference. Data from days 90 and 130 were analyzed separately using ANOVA in SAS. Maternal nutrient restriction during mid-gestation increased (P = 0.04) net umbilical glucose uptake but, maternal nutrient restriction during late-gestation decreased (P = 0.02) net umbilical glucose uptake. Net umbilical essential amino acid uptake decreased (P = 0.03) with nutrient restriction during mid-gestation; however, net umbilical uptakes of Phe (P = 0.02), Thr (P = 0.05), Met (P = 0.09), and His (P = 0.08) increased or tended to increase after nutrient restriction during late-gestation. These data demonstrate that net umbilical glucose and amino acid uptakes were influenced by the timing of nutrient restriction during mid- to late-gestation. Elevated net umbilical glucose uptake after mid-gestational nutrient restriction was sustained throughout late-gestation, independent of late-gestational feeding level. Long-term adaptations in umbilical glucose uptake may have implications for prenatal and postnatal growth and development of the offspring.

Maternal nutrient restriction during late gestation reduces vigor and alters blood chemistry and hematology in neonatal beef calves.

Fall-calving primiparous beef females [body weight: 451 ± 28 (SD) kg; body condition score: 5.4 ± 0.7] were individually-fed either 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to parturition. Calves were reared naturally by their dams and monitored for latency times from birth to first sternal recumbency, attempt to stand, and stand; vigor scores were assigned at 2, 5, 10, and 20min of age. Rectal temperatures and jugular blood were obtained at 0 (pre-suckling), 6, 12, 24, and 48h of age, and blood chemistry, hematology, cortisol, and insulin were determined. Data were analyzed with fixed effects of late gestational nutritional plane (single data point) or nutritional plane, hour, and their interaction (data over time, repeated measures). Calving date was a fixed effect; calf sex was included when P < 0.25. We previously reported that late gestational nutritional plane did not affect gestation length or calf size at birth, but calving assistance and fetal malpresentations occurred more often in NR. Nutritional plane did not affect (P = 0.65) duration of parturition, but calves born to NR dams had slower times to attempt to stand (P = 0.09), slower times to stand (P = 0.02), and had poorer 20min vigor scores (P = 0.05). Serum immunoglobulin G and A concentrations at 48h were greater (P ≤ 0.03) for NR calves. Rectal temperature of NR calves was less (P = 0.02) at 0h, but greater (P = 0.04) at 24h compared with CON. Circulating glucose, non-esterified fatty acids, triglycerides, cortisol, and insulin were not affected by nutritional plane (P ≥ 0.18). Total protein and globulin from 6 to 48h were greater (P ≤ 0.02) in NR calves. Calves from NR dams had greater (P < 0.08) gamma-glutamyl transferase at 6, 12, and 48h. Serum aspartate aminotransferase was greater (P ≤ 0.07) from 0 to 24h and creatine kinase was greater (P ≤ 0.04) from 6 to 24h in NR calves. At 0h, potassium was greater (P = 0.03) in NR calves. Calves born to CON had greater chloride (P = 0.08; main effect), sodium (P ≤ 0.09) from 0 to 48h, and anion gap (P = 0.02) at 6h. Hematocrit from 6 to 24h and red blood cells and hemoglobin at 6 and 12h were greater (P ≤ 0.09) in CON calves. These data indicate that nutrient restriction during late gestation resulted in less vigorous calves with more indicators of trauma in early life.

Effects of maternal high-fat diet on fetal growth, placental nutrient transporters and circular RNA expression profiles.

Epidemiological and experimental studies suggest that there is a strong correlation between maternal high-fat diet and fetal-placental development. The current study aims to investigate the effects of maternal high-fat diet on fetal growth, placental nutrient transporters and circular RNA expression profiles in a mouse model. Forty C57BL/6 female mice were randomly assigned to two groups, fed either a control (10% fat for energy) diet (CON) or a high-fat (60% fat for energy) diet (HFD) for 4 weeks before mating and throughout pregnancy, and were killed on day 19.5 of pregnancy. The serum glucose, total cholesterol and low-density lipoprotein, the glucolipid metabolism-related hormones, and the insulin resistance index were significantly increased. High-throughput sequencing showed that differentially expressed circRNAs (DE circRNAs) in the placenta can regulate various biological processes, cellular components, and molecular functions through various energy metabolism pathways, and mmu-let-7g-5p was found to target and bind to multiple DE circRNAs. In addition, this study also predicted that various circRNAs with protein coding functions can regulate maternal placental nutrient transport. In general, the ceRNA (circRNAs-miRNAs-mRNAs) regulatory network of maternal placental nutrient transport constructed in this study is of great significance for further understanding the effect of maternal nutrition on fetal growth in the future.

Placental Fatty Acid Metabolism and Transport in a Rat Model of Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a form of heightened insulin resistance triggered during gestation. This study examines how insulin resistance alters placental long-chain polyunsaturated fatty acid (LCPUFA) transport and metabolism in a rat model of lean GDM. Pregnant Sprague Dawley rats were administered with S961, an insulin receptor antagonist (30 nmol/kg s.c. daily), or vehicle from gestational day (GD) 7 to 20. Daily maternal body weight, food, and water intake were measured. Blood pressure assessment and glucose tolerance test were done on GD20. Fetal plasma and placenta were collected on GD20 and processed for fatty acid measurement using LC-mass spectrometry. The expression of fatty acid metabolism-related genes in the placenta was assessed using RT2 Profiler PCR arrays. The results were validated by qRT-PCR. Blockade of insulin receptors with S961 in pregnant rats resulted in glucose intolerance with increased fasting glucose and insulin levels. Maternal body weight gain and food and water intake were not affected; however, S961 significantly increased maternal blood pressure and heart rate. The placenta n3 and n6 LCPUFA concentrations were significantly decreased by 8% and 11%, respectively, but their levels in the fetal plasma were increased by 15% and 4%. RT2 profiler arrays revealed that placental expressions of 10 genes related to fatty acid β-oxidation (Acaa1a, Acadm, Acot2, Acox2, Acsbg1, Acsl4, Acsm5, Cpt1b, Eci2, Ehhadh) and 3 genes related to fatty acid transport pathway (Fabp2, Fabp3, Slc27a3) were significantly upregulated. In summary, lack of insulin action increased the expression of genes related to placental fatty acid β-oxidation and transport with an increased transfer of LCPUFA to the fetus. The increased lipid levels routed toward the fetus may lead to fat adiposity and later-life metabolic dysfunction.

母亲孕期营养素补充与母婴不良结局的相关研究进展

母亲孕期营养素补充与母婴不良结局的相关研究进展