Prenatal Diets Research Articles

The Effects of Prenatal Diet on Calf Performance and Perspectives for Fetal Programming Studies: A Meta-Analytical Investigation.

Simple SummaryPrenatal nutrition can reshape an animal’s developmental trajectory, with persistent long-term consequences for the progeny. In prenatal life, the effects induced by the intrauterine conditions can be expressed as changes in offspring growth and meat quality. Thus, there are diverse sources of variations that contribute to the variations reported for fetal-programming responses in beef cattle, making it difficult to interpret and apply the results. In this sense, finding a common factor among the studies with which to group them may offer an opportunity to quantify the fetal-programming effects holistically and to obtain more applicable responses. With the increasing number of publications, it is important to summarize the quantitative measurements available in the scientific literature. In the present study, data from 35 publications were used. We verified that there is a gap related to the effects of maternal nutrition to females, at the beginning of gestation, and in zebu and crossbred animals, indicating new perspectives for future fetal-programming studies. In summary, our findings highlight an association between prenatal energy and protein supply and its effects on the offspring birth weight, weaning weight, and the daily weight gain of pregnant beef cows during pregnancy.This meta-analysis aimed to identify knowledge gaps in the scientific literature on future fetal-programming studies and to investigate the factors that determine the performance of beef cows and their offspring. A dataset composed of 35 publications was used. The prenatal diet, body weight (BW), average daily gain (ADG) during pregnancy, and calf sex were elicited as possible modulators of the beef cows and their offspring performance. Then, the correlations between these variables and the outcomes of interest were investigated. A mixed multiple linear regression procedure was used to evaluate the relationships between the responses and all the possible explanatory variables. A knowledge gap was observed in studies focused on zebu animals, with respect to the offspring sex and the consequences of prenatal nutrition in early pregnancy. The absence of studies considering the possible effects promoted by the interactions between the different stressors’ sources during pregnancy was also detected. A regression analysis showed that prenatal diets with higher levels of protein improved the ADG of pregnant beef cows and that heavier cows give birth to heavier calves. Variations in the BW at weaning were related to the BW at birth and calf sex. Therefore, this research reinforces the importance of monitoring the prenatal nutrition of beef cows.

Prenatal Low-Protein and Low-Calorie Diets Differentially Alter Arcuate Nucleus Morphology in Newborn Male Rats.

BackgroundMalnutrition during the early stages of development produces alterations that can compromise the functioning of the hypothalamic circuits that regulate food intake. The purpose of this study is to analyze the effects that a low-protein and low-calorie diet has on the morphology of the arcuate nucleus (ARC) of the hypothalamus in newborn male and female rats.MethodsOn gestational day 6 (G6), six pregnant rats were divided into two groups. One group was made up of three pregnant rats, which were fed ad libitum with a control diet (20% casein), and the other one was made up of three pregnant rats, which were fed ad libitum with a low-protein diet (8% casein) and 30% of a calorie-restricted diet. On the day of birth, pups were sacrificed, resulting in four experimental groups: control male, control female, low-protein and low-calorie diet male, and low-protein and low-calorie diet female (n = 5 in each group). The volume and number of neurons, together with the neuronal density and number of apoptotic cells, were measured.ResultsMales on a low-protein and low-calorie diet showed a significant increase in the number of neurons and in the neuronal density of the ARC with regard to the rest of the groups studied. These increases were also reflected in the posterior part of the nucleus. Although the existence of sexual dimorphism was not detected in any of the parameters studied in the control groups, the number of neurons and neuronal density showed differences between males and females fed with a low-protein and low-calorie diets due to the increase in the number of neurons shown by the male. No significant differences were found in the number of apoptotic cells.ConclusionOur results show that a low-protein and low-calorie diet during the prenatal stage produces alterations in the ARC of the hypothalamus in newborn animals and, more importantly, that the effects of malnutrition are evident in males but not in females. Therefore, it is essential to follow a balanced diet during the early stages of life to ensure optimal development of the neural circuits that regulate eating.

Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner

Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome.

Resveratrol intake during pregnancy and lactation re-programs adiposity and ameliorates leptin resistance in male progeny induced by maternal high-fat/high sucrose plus postnatal high-fat/high sucrose diets via fat metabolism regulation

BackgroundMaternal obesity is an emerging problem in the modern world. Growing evidence suggests that intrauterine high-fat (HF) exposure may predispose progeny to subsequent metabolic challenges. Progeny born to mothers who ate an HF diet also tends to eat an HF diet when growing and aggravate metabolic issues. Thus, the generational transmission of obesity is cyclical. Developing a strategy to prevent the occurrence of metabolic syndrome related to prenatal and/or postnatal HF diet is important. In this study, the reprogramming effects of maternal resveratrol treatment for the progeny with maternal HF/postnatal HF diets were investigated.MethodsSprague-Dawley dams were fed either a control or a high-fat/high sucrose diet (HFHS) from mating to lactation. After weaning, the progeny was fed chow or an HF diet. Four experimental groups were yielded: CC (maternal/postnatal control diet), HC (maternal HF/postnatal control diet), CH (maternal control/postnatal HFHS diet), and HH (maternal/postnatal HFHS diet). A fifth group (HRH) received a maternal HFHS diet plus maternal resveratrol treatment and a postnatal chow diet to study the effects of maternal resveratrol therapy. ResultsMaternal resveratrol treatment lessened the weight and adiposity of progeny that were programmed by combined prenatal and postnatal HFHS diets. Maternal resveratrol therapy ameliorated the decreased abundance of the sirtuin 1 (SIRT1) enzyme in retroperitoneal tissue and the altered leptin/soluble leptin receptor ratio of progeny. Maternal resveratrol therapy also decreased lipogenesis and increased lipolysis for progeny.ConclusionsMaternal resveratrol intervention can prevent adiposity programmed by maternal and postnatal HFHS diets by inducing lipid metabolic modulation. This study offers a novel reprogramming role for the effect of maternal resveratrol supplements against obesity.

Testis-specific changes in gene expression of post-pubertal beef bulls divergent for residual feed intake and exposure to different pre-natal diets

Context Selection for residual feed intake (RFI) and its impact on male reproductive development has had mixed reviews in the past. Our previous studies demonstrated earlier puberty, larger testes and greater percentage of progressively motile sperm in high-RFI bulls. However, the molecular mechanisms within testes of bulls with varying RFI remain unclear. Aims To determine the effect of RFI and pre-natal diet on the expression patterns of testicular genes and use this information to explain differences observed across RFI. Methods The study included 25 purebred-Angus bulls with a genetic background of either high or low RFI and fed either normal or low pre-natal nutrition from 30 to 150 days post conception. After slaughter (17 months), testicular tissue was recovered, and RNA was extracted and sequenced. Key results Of 19218 expressed genes, 17 were differentially expressed for RFI (including PLCD1, INPP4B), with no differences being observed for pre-natal diet or diet × RFI interaction (false discovery rate) < 0.1%). KEGG pathway analysis indicated that differentially expressed genes were associated with inositol phosphate metabolism, and phosphatidylinositol signalling. On the basis of a candidate gene-expression study, IGF1R was upregulated in high-RFI bulls (P < 0.1). Conclusions Increased expression of IGF1R and lowered PLCD1 and INPP4B expression could activate PI3K–Akt signalling responsible for cell growth, proliferation and steroid metabolism in high-RFI bulls. Implications Selecting bulls for feed efficiency might affect molecular networks associated with reproduction and fertility.

Prenatal Nutritional Intervention Reduces Autistic-Like Behavior Rates Among Mthfr-Deficient Mice.

The causes and contributing factors of autism spectrum disorders (ASD) are poorly understood. One gene associated with increased risk for ASD is methylenetetrahydrofolate-reductase (MTHFR), which encodes a key enzyme in one carbon (C1) metabolism. The MTHFR 677C > T polymorphism reduces the efficiency of methyl group production with possible adverse downstream effects on gene expression. In this study, the effects of prenatal and/or postnatal diets enriched in C1 nutrients on ASD-like behavior were evaluated in Mthfr-deficient mice. Differences in intermediate pathways between the mice with and without ASD-like behaviors were tested. The findings indicate that maternal and offspring Mthfr deficiency increased the risk for an ASD-like phenotype in the offspring. The risk of ASD-like behavior was reduced in Mthfr-deficient mice supplemented with C1 nutrients prenatally. Specifically, among offspring of Mthfr+/- dams, prenatal diet supplementation was protective against ASD-like symptomatic behavior compared to the control diet with an odds ratio of 0.18 (CI:0.035, 0.970). Changes in major C1 metabolites, such as the ratios between betaine/choline and SAM/SAH in the cerebral-cortex, were associated with ASD-like behavior. Symptomatic mice presenting ASD-like behavior showed decreased levels of GABA pathway proteins such as GAD65/67 and VGAT and altered ratios of the glutamate receptor subunits GluR1/GluR2 in males and NR2A/NR2B in females. The altered ratios, in turn, favor receptor subunits with higher sensitivity to neuronal activity. Our study suggests that MTHFR deficiency can increase the risk of ASD-like behavior in mice and that prenatal dietary intervention focused on MTHFR genotypes can reduce the risk of ASD-like behavior.

Maternal Metabolic Complications in Pregnancy and Offspring Behavior Problems at 2Years of Age.

Objectives Prenatal maternal metabolic problems such as pre-pregnancy adiposity, excess gestational weight gain, and gestational diabetes mellitus (GDM) are associated with an increased risk of psychopathology in offspring. We examined whether these exposures were linked to symptoms of emotional and behavioral problems in offspring at 2years of age, or if associations were due to confounding variables. Methods Data from 815 mother-child pairs enrolled at the Edmonton site of the Canadian Healthy Infant Longitudinal Development cohort were used to examine associations between gestational metabolic complications and scores on the externalizing and internalizing scales of the Child Behavior Checklist (CBCL-1½ to 5) at age two. Associations between maternal metabolic complications and offspring psychopathology were assessed before and after adjustment for gestational diet, socioeconomic status (SES), postpartum depression (PPD), prenatal smoking and breastfeeding. Results Pre-pregnancy body mass index and GDM, but not gestational weight gain, predicted more offspring externalizing and internalizing problems. However, after adjustment for confounding variables, these associations were no longer statistically significant. Post-hoc analyses revealed that gestational diet accounted for unique variance in both externalizing (semi-partial rdiet = - 0.20, p < 0.001) and internalizing (semi-partial rdiet = - 0.16, p = 0.01) problems. PPD and SES also accounted for a similar amount of variance for both externalizing (semi-partial rPPD = 0.17, p < 0.001; rses = - 0.11, p = 0.03) and internalizing problems (semi-partial rPPD = 0.21, p < 0.001; rses = - 0.14, p = 0.004). Conclusions for Practice Since the confounding effect of gestational diet persisted after adjustment for, and was similar in magnitude to, SES and PPD, future research should consider the impact of unhealthy prenatal diets on offspring neurodevelopment.

Regulation of cerebral arterial BKCa channels by angiotensin II signaling in adult offspring exposed to prenatal high sucrose diets.

Prenatal insults have been shown to affect vascular functions, leading to increased risks of cardiovascular diseases in offspring. The present study determined whether high sucrose (HS) intake in pregnancy affected central vascular functions in middle cerebral artery (MCA) of offspring. Sprague-Dawley rats were fed a standard food and tap water with normal or high (20%) sucrose content during pregnancy. Offspring were maintained with normal diets and tap water. Central vascular functions and related ion channels were assessed in male offspring at 5 months old. Compared with the control, angiotensin II (AII)-induced vasoconstrictions were significantly higher in the MCA of the offspring exposed to prenatal HS. In the MCA, large conductance Ca2+-activated K+ channels (BKCa) currents were decreased with a reduction of opening frequency, sensitivity to intracellular Ca2+/membrane voltage, and BKβ1 expression. mRNA levels of AT1α and AT2, as well as AT1/AT2 ratio, were significantly increased in the MCA of offspring following exposure to prenatal HS diets. The data suggested that prenatal HS diets could alter microvascular activities in the MCA, probably via changes of BKCa channels in the brain.

Intergenerational impact of paternal lifetime exposures to both folic acid deficiency and supplementation on reproductive outcomes and imprinted gene methylation.

Do paternal exposures to folic acid deficient (FD), and/or folic acid supplemented (FS) diets, throughout germ cell development adversely affect male germ cells and consequently offspring health outcomes? Male mice exposed over their lifetimes to both FD and FS diets showed decreased sperm counts and altered imprinted gene methylation with evidence of transmission of adverse effects to the offspring, including increased postnatal-preweaning mortality and variability in imprinted gene methylation. There is increasing evidence that disruptions in male germ cell epigenetic reprogramming are associated with offspring abnormalities and intergenerational disease. The fetal period is the critical time of DNA methylation pattern acquisition for developing male germ cells and an adequate supply of methyl donors is required. In addition, DNA methylation patterns continue to be remodeled during postnatal spermatogenesis. Previous studies have shown that lifetime (prenatal and postnatal) folic acid deficiency can alter the sperm epigenome and increase the incidence of fetal morphological abnormalities. Female BALB/c mice (F0) were placed on one of four amino-acid defined diets for 4 weeks before pregnancy and throughout pregnancy and lactation: folic acid control (Ctrl; 2 mg/kg), 7-fold folic acid deficient (7FD; 0.3 mg/kg), 10-fold high FS (10FS, 20 mg/kg) or 20-fold high FS (20FS, 40 mg/kg) diets. F1 males were weaned to their respective prenatal diets to allow for diet exposure during all windows of germline epigenetic reprogramming: the erasure, re-establishment and maintenance phases. F0 females were mated with chow-fed males to produce F1 litters whose germ cells were exposed to the diets throughout embryonic development. F1 males were subsequently mated with chow-fed female mice. Two F2 litters, unexposed to the experimental diets, were generated from each F1 male; one litter was collected at embryonic day (E)18.5 and one delivered and followed postnatally. DNA methylation at a global level and at the differentially methylated regions of imprinted genes (H19, Imprinted Maternally Expressed Transcript (Non-Protein Coding)-H19, Small Nuclear Ribonucleoprotein Polypeptide N-Snrpn, KCNQ1 Opposite Strand/Antisense Transcript 1 (Non-Protein Coding)-Kcnq1ot1, Paternally Expressed Gene 1-Peg1 and Paternally Expressed Gene 3-Peg3) was assessed by luminometric methylation analysis and bisulfite pyrosequencing, respectively, in F1 sperm, F2 E18.5 placenta and F2 E18.5 brain cortex. F1 males exhibited lower sperm counts following lifetime exposure to both folic acid deficiency and the highest dose of folic acid supplementation (20FS), (both P < 0.05). Post-implantation losses were increased amongst F2 E18.5 day litters from 20FS exposed F1 males (P < 0.05). F2 litters derived from both 7FD and 20FS exposed F1 males had significantly higher postnatal-preweaning pup death (both P < 0.05). Sperm from 10FS exposed males had increased variance in methylation across imprinted gene H19, P < 0.05; increased variance at a few sites within H19 was also found for the 7FD and 20FS groups (P < 0.05). While the 20FS diet resulted in inter-individual alterations in methylation across the imprinted genes Snrpn and Peg3 in F2 E18.5 placenta, ≥50% of individual sites tested in Peg1 and/or Peg3 were affected in the 7FD and 10FS groups. Inter-individual alterations in Peg1 methylation were found in F2 E18.5 day 10FS group brain cortex (P < 0.05). Not applicable. The cause of the increase in postnatal-preweaning mortality was not investigated post-mortem. Further studies are required to understand the mechanisms underlying the adverse effects of folic acid deficiency and supplementation on developing male germ cells. Genome-wide DNA and histone methylome studies as well as gene expression studies are required to better understand the links between folic acid exposures, an altered germ cell epigenome and offspring outcomes. The findings of this study provide further support for paternally transmitted environmental effects. The results indicate that both folic acid deficiency and high dose supplementation can be detrimental to germ cell development and reproductive fitness, in part by altering DNA methylation in sperm. This study was supported by a grant to J.M.T. from the Canadian Institutes of Health Research (CIHR #89944). The authors declare they have no conflicts of interest.

Maternal high-sucrose diets altered vascular large-conductance Ca2+-activated K+ channels via reactive oxygen species in offspring rats.

Overnutrition during pregnancy could increase risks of cardiovascular diseases in late life. This study investigated whether and how reactive oxygen species (ROS) may influence functions of large-conductance Ca2+-activated K+ channels (BKCa) in the offspring exposed to prenatal high sucrose (HS). We found that prenatal HS diets significantly increased phenylephrine (PE)-induced vessel contractions in mesenteric arteries of the adult offspring. Pretreatment with iberiotoxin (BKCa blocker, IBTX) significantly increased PE-mediated vascular contractions in the control, not in the HS group. Electrophysiological studies demonstrated that BKCa current density and single-channel current were reduced in the vascular smooth muscle cells (VSMCs) of the HS offspring. The expression of BKCa alpha, beta1 subunits in mesenteric arteries was decreased in the HS offspring, indicating that both activity and number of BKCa channels in HS offspring were reduced. Superoxide production and NADPH oxidase (NOX)4 of the HS offspring were elevated. Following inhibiting NOX by apocynin, vasoconstriction in the HS offspring was weakened and the reduced currents in the VSMCs were improved with altered protein kinase B (AKT) pathway. The results suggested that NOX4-derived ROS might inhibit the offspring vascular BKCa channel activity via AKT pathway.

Maternal high salt diet altered Adenosine-mediated vasodilatation via PKA/BK channel pathway in offspring rats.

High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries. Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K+ channels and Adenosine signal pathways. Adenosine-mediated vasodilatation was reduced in coronary arteries in HS. There was no difference in gene expression of A2A receptors between the two groups. After pretreatment with PKA inhibitor, vasodilatation to Adenosine was decreased to a smaller extent in HS than that in control. Forskolin (activator of adenylate cyclase)-mediated vasodilatation was decreased in HS. Iberiotoxin (large-conductance Ca2+ -activated K+ channel [BK channel] inhibitor) attenuated Forskolin-induced vasodilatation in control, not in HS group. Currents of BK channels decreased in coronary artery smooth muscle cells, and PKA-modulated BK channel functions were declined. Protein levels of BK β1 and PKA C-subunits in coronary arteries of HS offspring were reduced. Prenatal HS diets altered Adenosine-mediated coronary artery vasodilatation in the offspring, which was linked to downregulation of cAMP/PKA/BK channel pathway.

Associations between Prenatal and Early Childhood Fish and Processed Food Intake, Conduct Problems, and Co-Occurring Difficulties

Little is known about early life diet as a risk factor for early-onset persistent conduct problems (EOP CP). To investigate this, we used data from the Avon Longitudinal Study of Parents and Children, a UK-based prospective epidemiological birth cohort. 5727 mother-child pairs (49.9 % boys) monitored since pregnancy (delivery date between 1 April, 1991 and 31 December, 1992) reported intake of fish and processed foods at 32 weeks gestation and, for the child, at 3 years; EOP (n = 666) and Low conduct problem (Low CP, n = 5061) trajectories were measured from 4 to 13 years; hyperactivity and emotional difficulties were assessed in childhood (4–10 years) and early adolescence (12–13 years), in addition to potential confounding factors (family adversity, birth complications, income). Compared to Low CP, mothers of EOP children consumed less fish (p < 0.01) and more processed food (p < 0.05) prenatally, while EOP children consumed more processed food at 3 years (p < 0.05). For EOP, but not Low CP children, consuming less than two servings/week of fish (vs. two or more servings/week, p < 0.05), and one or more servings/day of processed food (vs. less than one serving/day, p < 0.01), was associated with higher emotional difficulties in early adolescence. Conclusions: Findings suggest that prenatal and postnatal diets high in processed food, and low in fish, associate with an EOP CP trajectory and co-occurring difficulties in early adolescence. As small effect size differences were found, further studies are needed to investigate the long-term impact of early unhealthy diet.

Effect of the prenatal maternal environments and diets on cord blood interleukin-4 and interferon -gamma: A pilot study.

TThe environment of a pregnant woman can affect not only fetal growth and development, but also diseases in childhood. Neonatal cord blood cytokines are commonly used to evaluate the immune development of neonates. The purpose of this study was to evaluate the effects of the environment and diet during pregnancy on IL-4 and IFN-γ in neonatal cord blood. A total of 111 pregnant women participated in this study from April to November 2010. Allergy history, sensitization assessed by the skin prick test, dietary intake and indoor environment were evaluated. IL-4 and IFN-γ levels were measured in the complete cord blood of neonates using real-time PCR. There were 54 pregnant women with allergic disease. Both IL-4 and IFN-γ levels in neonatal cord blood were higher in samples from allergic mothers than in non-allergic mothers (p<0.05). The indoor environment and nutrient intake were not different between allergic and non-allergic mothers, except regarding carpet use. When the cytokine levels were divided into quartiles, lower folate and vitamin B6 intake was associated with the highest levels of IL-4 in neonatal cord blood (p<0.05), and higher folate and vitamin B6 intake was associated with highest levels of IFN-γ in neonatal cord blood. In this study, a strong association between IL-4 and IFN-γ levels in cord blood and the intake of folate and vitamin B6 was found, which indicates that food intake during pregnancy might have a strong influence on IL-4 and IFN-γ levels in cord blood, to a greater extent than environmental factors.

Preventive effects of individualized dietary and exercise interventions on gestational diabetes mellitus in gravidas with overweight and obesity before pregnancy

Objective To investigate the preventive effects of individualized dietary and exercise intervention on gestational diabetes mellitus (GDM) in gravidas with overweight and obesity before pregnancy. Methods A quasi-experimental trial was conducted in a level three class A hospital in Beijing. A total of 66 pregnant women, who met the inclusion criteria and went to outpatient during gestational weeks 8-12, were divided into experimental group (n=32) and control group (n=34) according to the sequence of hospitalization time. The patients of control group were given prenatal diets, excises and the knowledge education of body weight increasing, while the patients of experimental group were taken individualized interventions and weekly telephone follow-up. We compared 50 glucose screening test positive rate between two groups when gravidas were in gestational 24-28 weeks. Results The incidences of 50 glucose screening test positive rate and GDM were 53.1% and 28.1% in the experimental group, while they were 82.4% and 55.9% respectively in the control group(χ2=6.491, 5.200; P<0.05). Conclusions Individualized dietary and exercise direction can effectively decrease the incidence of GDM for gravidas with overweight and obesity before pregnancy. Key words: Diabetes mellitus, Gestation; Overweight or obese before pregnant; Individualized diet guide; Individualized exercise

Impact of Prenatal Exposure to Humanized High Fat Diets on Murine Metabolic Phenotype

Prenatal exposures, including maternal diet, can alter risk for metabolic disease across the lifecourse. This study examines the effects of 2 prenatal high fat diets (HFDs) on mice offspring weight, nutrient utilization, and activity at 2 and 4 months of age. Two HFDs (43% fat kcal) were developed to mirror human intake: 1) Western (W) and 2) Mediterranean (M). Dams (n=44) were randomized to W, M, or Control (C) (7% fat) 2 wks prior to mating through pregnancy and lactation; pups were weaned onto C diet. One male (n=36) and 1 female (n=35) pup/litter were followed longitudinally with weekly weights and comprehensive phenotyping at 2 and 4 mos of age. ANOVA with Tukey's post-hoc analysis compared pups' mean metabolic outcomes across maternal prenatal diet groups. Prenatal HFD had a greater impact on females than males. M females were less ambulatory (p=0.046, 0.021) with less horizontal (p=0.023, 0.063) and vertical (p=0.035, 0.031) activity than C females at 2 and 4 mos, respectively. A similar trend was observed in 2 mo M males with less ambulatory (p=0.064) and horizontal (p=0.063) activity; by 4 mos, no activity differences were noted. At 4 mos, glucose oxidation (p=0.044) and respired CO2 (p=0.016) were lower in M females vs. C, consistent with increased utilization of fat as a primary fuel. All significant findings were during the light cycle, suggesting HFD impacts resting activity. MANOVA analysis found increased weight in M females but not males (p=0.047 and p=0.260). Thus, prenatal HFD alters female activity and nutrient utilization into early adulthood. A third round of phenotyping will be performed at 8 mos to characterize life course effects.

Enriching the Diet In N‐3 Polyunsaturated Fatty Acids Reduces Adiposity and Adipocyte Size in a Broiler Chick Model for Childhood Obesity

Epidemiological studies suggest that enriching prenatal and perinatal diets in long‐chain omega‐3 polyunsaturated fatty acids (LC n‐3 PUFA) may be a tool with which to reduce adiposity, improve metabolic status and reduce the risk of childhood obesity. We used broiler chickens, which rapidly deposit adipose tissue post‐hatch and share a number of metabolic features with humans, to test the hypothesis that consumption of diets enriched in LC n‐3 PUFA during the early post‐hatch period of rapid adipose development reduces adiposity. From seven to 21 days of age,Cobb500 broiler chicks (n=10/group) were fed isocaloric diets formulated using either lard (primarily saturated), corn oil (primarily monounsaturated), flaxseed oil (PUFA, enriched in alpha linolenic acid (ALA, 18:3, n‐3)), or fish oil (PUFA, enriched in eicosapentaenoic acid (EPA, 20:5, n‐3) and docosahexaenoic acid (DHA, 22:6, n‐3)), each at 8% by weight. Abdominal fat pad weight, but not body weight, was significantly (p=0.0327) lower in birds fed the fish oil diet (21.3g±5.5) than those fed lard (26.7g±5.9), but did not differ in birds fed flax and corn‐oil based diets relative to lard. Fish oil also significantly reduced abdominal adipocyte size compared to all other diets (p&lt;0.05). Subcutaneous adipocyte size was significantly smaller in corn, flax and fish oil groups relative to lard (p&lt;0.05). Plasma non‐esterified fatty acid levels, as a reflection of lipolysis, increased in birds fed fish oil diets as compared to lard diets (p=0.0194). Collectively, our data suggest that altering the type of fatty acids consumed during childhood may attenuate adipose deposition and adipocyte size, which could have benefits in reducing childhood obesity.

Hippocampal apoptosis involved in learning deficits in the offspring exposed to maternal high sucrose diets

The hippocampus plays a crucial role in learning and memory, and neuronal apoptosis in the hippocampus contributes to learning deficits. Metabolism problems in pregnancy related to excessive fuel consumption (e.g., high fat, high sugar) may influence cognitive and behavioral functions in the offspring by affecting developing brain cells. This study determined the influence of maternal high sucrose (HS) diets on behavior and hippocampal neurons in the young offspring. The ratio of brain weight to body weight in the offspring exposed to prenatal HS diets was significantly decreased; the Morris water maze showed that the offspring exposed to prenatal HS diets exhibited increased escape latencies and path length during navigation testing, while there were no changes in time spent in the target quadrant and number of target approaches. In the offspring exposed to prenatal HS, TUNEL-positive cells were significantly increased in CA1, CA2 and CA3 of the hippocampus; protein expression of insulin-like growth factor-I, PI3K and phosphorylated Akt was significantly decreased, while caspase-3 and N-methyl-d-aspartate receptors were significantly increased in the hippocampus, and there was no change in expression of Bcl-2 and Akt. The results demonstrated that prenatal HS diets could induce the spatial acquisition deficits in the young offspring associated with hippocampal apoptosis, and altered signaling factors for antiapoptosis in the hippocampus might play a critical role in cognition disorders in young children.

Maternal High-Salt Intake During Pregnancy Reprogrammed Renin–Angiotensin System-Mediated Cardiomyocyte Apoptosis in the Adult Offspring Heart

Excess salt intake during pregnancy may alter fetal organ structures and functions leading to increased risks in the development of cardiovascular diseases in later life. The present study determined whether and how the prenatal high-salt (HS) diets affect renin-angiotensin system (RAS) that may mediate cardiac cell death. Angiotensin II receptors, AT1 and AT2, protein expression was increased in the myocardium of the offspring exposed to prenatal HS; apoptotic cells appeared in the myocardium of the adult offspring. Mitochondrion was isolated in cell experiments, and the data showed cardiomyocyte apoptosis requiring cytochrome C release. Pretreating H9C2 cells with AT2 agonist CGP42112A induced cell apoptosis in DNA fragments and activated caspase 3. CGP42112A increased mitochondrion cytochrome C release and apoptosis in the cells. Both in vitro and in vivo study demonstrated that cardiomyocyte apoptosis was related to AT2 activation. Prenatal HS diets may reprogram RAS that mediates apoptosis in the offspring myocardium, and AT2 may contribute to cardiomyocyte apoptosis via the cytochrome C release pathway.

F0 Prenatal/Lactation Diets Varying in Saturated Fat and Long-Chain Polyunsaturated Fatty Acids Alters the Insulin Sensitivity of F1 Rats Fed a High Fat Western Diet Post-weaning

Previous research has shown that prenatal diets rich in specific nutrients (e.g. taurine, omega-3 fatty acids) may provide protective cardiometabolic effects for adult offspring. The purpose of the current study was to investigate the potential of a prenatal-lactation diet rich in omega-3 longchain polyunsaturated fatty acids (omega-3 LC PUFAs) to improve metabolic function in offspring fed a high saturated fat “Western” diet postweaning. We compared growth and metabolic biomarkers of three groups of Sprague Dawley rat offspring all weaned to a high saturated fat “Western” (Western) diet, but whose mothers were fed one of three different diets during pregnancy-lactation: 1) omega-3 “PUFA”-rich (PUFA/Western); 2) control (Control/Western); and 3) high saturated fat “Western” (Western/Western). PUFA/Western offspring had significantly lower fasting insulin (P < 0.01) and HOMA-IR (P < 0.01), and lower mean plasma triglycerides than Western/ Western animals. Additionally, mean HOMA-IR, fasting plasma insulin, and triglycerides were 19%, 10% and 14% lower, respectively, than those of Control/Western animals, although these differences were not statistically significant. Western/Western adult offspring had the highest fasting plasma insulin, triglycerides, and insulin-resistance (HOMA-IR) of the three groups. Our results indicated that a maternal omega-3 PUFA-rich diet during pregnancy-lactation may provide modest protective metabolic effects for adult offspring, even when consuming a high energy and saturated fat diet.

Prenatal Low-Protein and Postnatal High-Fat Diets Induce Rapid Adipose Tissue Growth by Inducing Igf2 Expression in Sprague Dawley Rat Offspring1–3

Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes.