Maternal Nutrient Restriction Research Articles

Maternal nutrition altered embryonic MYOD1, MYF5, and MYF6 gene expression in genetically fat and lean lines of chickens.

ObjectiveThe objectives of this study were to evaluate the effects of daily feed intake during the laying period on embryonic myogenic differentiation 1 (MYOD1), myogenic factor 5 (MYF5), and myogenic factor 6 (MYF6) gene expression in genetically fat and lean lines of chickens.MethodsAn experiment in a 2×2 factorial design was conducted with two dietary intake levels (100% and 75% of nutrition recommendation) and two broiler chicken lines (fat and lean). Two lines of hens (n = 384 for each line) at 23th week of age were randomly divided into 4 treatments with 12 replicates of 16 birds. The experiment started at 27th week of age (5% egg rate) and ended at 54th week of age. Hatched eggs from the medium laying period were collected. Real time polymerase chain reaction analysis was used to analyse the MYOD1, MYF5, and MYF6 mRNA levels of E7, E9, E11, E13, and E15 body tissues and E17, E19, and E21 chest and thigh muscle samples.ResultsThe results indicated that there were significant effects of line, dietary intake, and interactions between them on MYOD1, MYF5, and MYF6 gene mRNA expression levels in embryonic tissues. Low daily feed intake did not change the expression trend of MYOD1 mRNA in either line, but changed the peak values, especially in lean line. Low daily feed intake altered the trend in MYF5 mRNA expression level in both lines and apparently delayed its onset. There was no apparent effect of low daily feed intake on the trends of MYF6 mRNA expression levels in either line, but it significantly changed the values on many embryonic days.ConclusionMaternal nutrient restriction affects myogenesis and is manifested in the expression of embryonic MYOD1, MYF5, and MYF6 genes. Long term selection for fat deposition in broiler chickens changes the pattern and intensity of myogenesis.

Maternal Nutrient Restriction Disrupts Gene Expression and Metabolites Associated with Urea Cycle, Steroid Synthesis, Glucose Homeostasis, and Glucuronidation in Fetal Calf Liver.

This study aimed to understand the mechanisms underlying the effects of maternal undernutrition (MUN) on liver growth and metabolism in Japanese Black fetal calves (8.5 months in utero) using an approach that integrates metabolomics and transcriptomics. Dams were fed 60% (low-nutrition; LN) or 120% (high-nutrition; HN) of their overall nutritional requirements during gestation. We found that MUN markedly decreased the body and liver weights of the fetuses; metabolomic analysis revealed that aspartate, glycerol, alanine, gluconate 6-phosphate, and ophthalmate levels were decreased, whereas UDP-glucose, UDP-glucuronate, octanoate, and 2-hydroxybutyrate levels were decreased in the LN fetal liver (p ≤ 0.05). According to metabolite set enrichment analysis, the highly different metabolites were associated with metabolisms including the arginine and proline metabolism, nucleotide and sugar metabolism, propanoate metabolism, glutamate metabolism, porphyrin metabolism, and urea cycle. Transcriptomic and qPCR analyses revealed that MUN upregulated QRFPR and downregulated genes associated with the glucose homeostasis (G6PC, PCK1, DPP4), ketogenesis (HMGCS2), glucuronidation (UGT1A1, UGT1A6, UGT2A1), lipid metabolism (ANGPTL4, APOA5, FADS2), cholesterol and steroid homeostasis (FDPS, HSD11B1, HSD17B6), and urea cycle (CPS1, ASS1, ASL, ARG2). These metabolic pathways were extracted as relevant terms in subsequent gene ontology/pathway analyses. Collectively, these results indicate that the citrate cycle was maintained at the expense of activities of the energy metabolism, glucuronidation, steroid hormone homeostasis, and urea cycle in the liver of MUN fetuses.

Effects of nutrient restriction during early or mid-gestation in bovine on placental development and miRNA expression in the cotyledon

The objective of this study was to determine effects of maternal nutrient restriction (NR) during early or mid-gestation on uterine composition and miRNA expression in cotyledons. Primiparous Angus-cross cows (n = 38) were synchronized and inseminated using male sexed semen, blocked by body condition score and body weight (BW), and assigned to treatments. Animals were fed either: control (CON; gain 1 kg/week) or NR (55% maintenance energy and crude protein requirements) based on BW. An initial set of animals were fed either NR (n = 8) or CON (n = 8) from day 30–110 of gestation. A second set of animals were fed CON (n = 8) d 30–190 (CON/CON); NR (n = 7) day 30–110 followed by CON day 110–190 (NR/CON); or CON (n = 7) day 30–110 followed by NR day 110–190 (CON/NR). Cows were harvested on day 110 or 190 of gestation to collect placental tissues. RNA was isolated from cotyledon samples (3 animals/group) prior to microarray analysis using known Bos taurus microRNA sequences. Relative microRNA abundance was analyzed via ANOVA. Maternal NR increased (P < 0.05) cotyledon weight and total placentome surface area irrespective of gestational day. At day 110 of gestation, 51 microRNAs were reduced while 91 microRNAs observed greater abundance (P < 0.05) in NR verses CON cotyledons. At day 190 of gestation, 40 microRNAs were reduced and 26 microRNAs were increased (P < 0.05) in both NR/CON and CON/NR verses CON cotyledons. Top KEGG pathway analysis included: axon guidance, endocytosis, neuroactive ligand receptor interaction, and MAPK signaling pathway. Early-gestation maternal NR altered microRNA abundance to a greater extent than mid-gestation NR.

Maternal food restriction during pregnancy affects offspring development and swimming performance in a placental live-bearing fish.

ABSTRACTHow pregnant mothers allocate limited resources to different biological functions such as maintenance, somatic growth, and reproduction can have profound implications for early life development and survival of offspring. Here, we examined the effects of maternal food restriction during pregnancy on offspring in the matrotrophic (i.e. mother-nourishment throughout gestation) live-bearing fish species Phalloptychus januarius (Poeciliidae). We fed pregnant females with either low or high food levels for 6 weeks and quantified the consequences for offspring size and body fat at birth and 1 week after birth. We further measured fast-start escape performance of offspring at birth, as well as swimming kinematics during prey capture at 0, 2 and 7 days after birth. We found that the length of maternal food restriction during pregnancy negatively affected offspring dry mass and lean dry mass at birth, as well as body fat gain during the first week after birth. Moreover, it impacted the locomotor performance of offspring during prey capture at birth and during the first week after birth. We did not observe an effect of food restriction on fast-start escape performance of offspring. Our study suggests that matrotrophic poeciliid fish are maladapted to unpredictably fluctuating resource environments, because sudden reductions in maternal food availability during pregnancy result in smaller offspring with slower postnatal body fat gain and an inhibition of postnatal improving swimming skills during feeding, potentially leading to lower competitive abilities after birth.

Differences in bovine placentome blood vessel density and transcriptomics in a mid to late-gestating maternal nutrient restriction model.

Prenatal development is reliant on a functioning placenta, which can be influenced by maternal nutrition. Moreover, the variation in cotyledonary capacity within an animal has not been fully examined to date. Therefore, the purpose of this study was to determine the effect of (1) placentome size and (2) maternal nutrient restriction on molecular, microscopic, and macroscopic features of bovine placentomes during late gestation. Pregnant cows (n=6) were placed into one of 2 treatments: CON (100% NRC) vs RES (60% of NRC) from day 140 until slaughter at day 240 of gestation. Placentomes of various sizes were perfused to assess macroscopic blood vessel density of the cotyledon. Microscopic imaging and RNA extraction for sequencing was performed. Macroscopic blood vessel density relative to placentome weight was not different (P=0.42) among small, medium, or large placentomes. Cotyledonary microscopic blood vessel number, area, and perimeter was increased (P<0.005) in high versus low blood perfusion areas. Differential expressed gene (DEG) analysis showed 209 upregulations and 168 downregulations in the RES group (P≤0.0001). Gene Ontology (GO) analysis showed that downregulated enriched terms were involved in blood vessel and mesenchymal stem cells development, whereas upregulated enriched terms were involved with translation and ribosomal function. This study demonstrates that placentome function is uniform across various placentome sizes within an animal. However, microscopic heterogeneity exists within each placentome. Maternal nutrient constraints alter placental transcriptomics which may yield compensatory mechanisms involved in nutrient transport including increased perimeter.

FoxO1 Regulates Neuropeptide Y and Pro-opiomelanocortin in the Hypothalamus of Rat Offspring Small for Gestational Age.

Adulthood obesity, diabetes, and metabolic diseases are associated with small for gestational age (SGA) newborns. This association could be related to abnormal appetite signaling pathways in the hypothalamus. This study investigated the appetite regulation by the hypothalamus of SGA newborns by establishing an SGA rat model and culturing SGA neural progenitor cells (NPCs) in vitro. Models of SGA were established by maternal food restriction embryonic day 10 (E10). At E18, postpartum day 1 (P1), and P5, hypothalamic neural precursor cells (NPCs) of offspring were cultured in vitro. Immunofluorescence, Western blot (WB), and qRT-PCR were used to assess NPY, POMC, and FoxO1 expression levels. The effects on mRNA expression of the FoxO1-specific inhibitor AS1842856 were examined. The results indicated that compared with controls, NPY was higher, and POMC was lower at embryonic day 18 (E18), postpartum day 1 (P1), and P5. The proliferation and migration of NPCs in the third ventricle of SGA hypothalami were lower than in controls. After treatment with the FoxO1 inhibitor AS1842856, the differences in the mRNA expression of NPY and POMC between the two groups disappeared. NPY and POMC mRNA levels in the SGA group treated with AS1842856 were not significantly different compared with the control group without AS1842856 treatment. In conclusion, SGA pups showed an increase in appetite-promoting NPY and a decrease in appetite-reducing POMC, probably contributing to adulthood weight gain, obesity, and endocrine disorders.

The degree of maternal nutrient restriction during late gestation influences the growth and endocrine profiles of offspring from beef cows

Context Cow–calf operations in Argentina are managed under extensive grazing condition and the quality of forages is often poor during the second half of gestation. The severity of nutrient restriction in bovine gestation, caused by seasonal pasture production, often results in poor production traits in progeny. Aims The objective of the current study was to determine whether different levels of maternal nutrient intake in beef cows during late gestation affect fetal and postnatal growth, glucose metabolism, and insulin-like growth factor 1 (IGF1) concentrations in offspring of beef cattle. Methods At 180 ± 4 days of gestation, multiparous Angus cows (n = 56) were blocked by bodyweight (BW) and expected calving date, and assigned to pens (2 or 3 cows/pen). Pens (n = 8 per treatment) were then randomly assigned to the following treatments: severely restricted (SR; 50% of net energy and 58% of CP requirements), moderately restricted (MR; 75% of net energy and 85% of CP requirements), or control (CON; 100% of net energy and 116% of CP requirements). Pen was the experimental unit and data were analysed by ANOVA or repeated measures analysis, as appropriate. After calving, all cows were managed in a single group until weaning. Key results Cow BW and body condition score decreased as nutritional restriction increased (P &lt; 0.05). At parturition, birth weight of calves from SR dams and MR dams was lower than that of calves from CON dams (P = 0.05; 4.9 kg and 2.1 kg respectively). Average daily gain of calves from birth to 24 days of age was higher (P = 0.01) in calves from SR dams than in calves from CON and MR dams. Calves from MR dams were lighter (P = 0.04) than were calves from SR and CON dams at weaning. Treatments did not affect milk production or composition (P &gt; 0.10) or glucose–insulin metabolism of offspring during lactation (P &gt; 0.10). Concentration of IGF1 tended to be lower in MR progeny than in SR and CON progeny during lactation (P = 0.09). Conclusions Late gestation maternal nutrient restriction, irrespective of the severity of the restriction, decreased birth weight of offspring; however, severe nutrient restriction induced early postnatal compensatory growth. Implications The severe nutritional restriction produced calves with weaning weights indistinguishable from the control cows due to early postnatal compensatory growth. However, the longer-term effects of nutritional restriction of the dam in the second half of pregnancy on metabolic and reproductive performance in replacement heifers or meat production/quality in steers is yet to be determined.

Placental mTOR Signaling and Sexual Dimorphism in Metabolic Health across the Lifespan of Offspring

Robust evidence of fetal programming of adult disease has surfaced in the last several decades. Human and preclinical investigations of intrauterine insults report perturbations in placental nutrient sensing by the mechanistic target of rapamycin (mTOR). This review focuses on pregnancy complications associated with placental mTOR regulation, such as fetal growth restriction (FGR), fetal overgrowth, gestational diabetes mellitus (GDM), polycystic ovarian syndrome (PCOS), maternal nutrient restriction (MNR), preeclampsia (PE), maternal smoking, and related effects on offspring birthweight. The link between mTOR-associated birthweight outcomes and offspring metabolic health trajectory with a focus on sexual dimorphism are discussed. Both human physiology and animal models are summarized to facilitate in depth understanding. GDM, PCOS and fetal overgrowth are associated with increased placental mTOR, whereas FGR, MNR and maternal smoking are linked to decreased placental mTOR activity. Generally, birth weight is reduced in complications with decreased mTOR (i.e., FGR, MNR, maternal smoking) and higher with increased mTOR (GDM, PCOS). Offspring display obesity or a higher body mass index in childhood and adulthood, impaired glucose and insulin tolerance in adulthood, and deficiencies in pancreatic beta-cell mass and function compared to offspring from uncomplicated pregnancies. Defining causal players in the fetal programming of offspring metabolic health across the lifespan will aid in stopping the vicious cycle of obesity and type II diabetes.

Mid- to late-gestational maternal nutrient restriction followed by realimentation alters development and lipid composition of liver and skeletal muscles in ovine fetuses.

Maternal nutrient restriction during gestation adversely affects offspring growth and development of liver and skeletal muscle tissues. Realimentation following nutrient restriction may alleviate these negative impacts on development but may alter metabolism and tissue composition. Forty-eight ewes, pregnant with singletons, were fed to meet 100% National Research Council (NRC) recommendations starting at the beginning of gestation. On day 50 of gestation, seven ewes were euthanized (BASE), and fetal liver, skeletal muscles, and blood samples were collected. The remaining animals were fed either 100% of NRC recommendations (CON) or 60% NRC recommendations (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternate diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, the remaining ewes were euthanized, and fetal samples were collected. At day 130 of gestation, maternal nutrient restriction during late-gestation (RES-RES and CON-RES) decreased fetal liver weight (P < 0.01) and cross-sectional area in triceps brachii (P = 0.01; TB), longissimus dorsi (P = 0.02; LM), and semitendinosus (P = 0.05; STN) muscles. Maternal nutrient restriction during mid-gestation increased hepatocyte vacuole size at day 130 of gestation. Late-gestational maternal nutrient restriction increased mRNA expression of insulin-like growth factor (IGF) binding protein-1 (P < 0.01), glycogen synthase 2 (P = 0.01; GYS2), and pyruvate dehydrogenase kinase 1 (P < 0.01; PDHK1) in the liver and IGF receptor 1 (P = 0.05) in the LM. Lipid concentration in the LM was decreased by late-gestational nutrient restriction (P = 0.01) and increased by mid-gestational nutrient restriction in STN (P = 0.03) and TB (P < 0.01). Principal component analysis of lipidomics data demonstrated clustering of principal components by day of gestation and elastic net regression identified 50, 44, and 29 lipids that classified the treatments in the fetal liver, LM, and blood, respectively. In conclusion, restricting maternal nutrition impacts fetal liver and muscle morphology, gene expression, and lipid metabolism, whereas realimentation attenuated some of these effects. Therefore, realimentation may be a viable strategy to reduce the impacts of nutrient restriction, but can lead to alterations in lipid metabolism in sheep.

PSV-2 Maternal nutrient restriction and re-alimentation influences liver and muscle tissue development and gene expression

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on fetal liver and muscle development, 48 pregnant ewes with singletons, were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, ewes (n = 7) were euthanized and fetal liver and skeletal muscle samples were collected. The remaining animals were fed either CON or 60% NRC requirements (RES), a subset were euthanized at day 90 of gestation (n = 7/treatment), and fetal samples obtained. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver was analyzed for general tissue morphology, and fetal skeletal muscles were analyzed for lipid accumulation. mRNA expression of growth and metabolic factors were quantified in liver and muscle tissues. Hepatocellular vacuolation was increased in RES-CON and RES-RES compared with CON-CON and CON-RES (P &amp;lt; 0.01). In semitendinosus and triceps brachii, intramyocellular lipid content increased 19% and 15%, respectively, in RES-CON and RES-RES compared with CON-CON and CON-RES (P£0.02) and in longissimus dorsi, lipid content was decreased 7% in CON-RES and RES-RES compared with CON-CON and RES-CON (P=0.01). In liver, insulin-like growth factor binding protein-1, glycogen synthase 2, and pyruvate dehydrogenase kinase 1 expression increased 1.92-fold, 1.45-fold, and 1.47-fold, respectively (P£0.03) in CON-RES and RES-RES compared with RES-CON and CON-CON. In LD, IGF1-R expression increased 3.19-fold in CON-RES and RES-RES compared with RES-CON and CON-CON (P = 0.05). These results demonstrate that maternal nutrient restriction followed by re-alimentation restores liver and muscle gene expression of growth and metabolic factors while negatively impacting liver composition and muscle lipid content potentially leading to altered tissue function and metabolism later in life. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

249 Effects of Maternal Nutrient Restriction During Late Gestation on Uterine Blood Flow and Placental Size in the Primiparous Bovine Dam

Abstract To determine effects of late gestational maternal nutrient restriction (NR) on uteroplacental blood flow and placental growth, primiparous fall-calving crossbred beef heifers [BW: 451 ± 28 (SD) kg; BCS: 5.4 ± 0.7] were individually-fed either 100% (control; CON; n = 12) or 70% (n = 13) of energy and protein requirements for maintenance, pregnancy, and growth during the last 120 days of gestation. Transrectal color Doppler ultrasonography of both uterine arteries was conducted pre-treatment and every 21 d during treatments. Placentas were split into ipsilateral and contralateral sides, dissected (cotyledonary vs. intercotyledonary), and dried. Data were analyzed with treatment, treatment initiation date, and calf sex (when P &amp;lt; 0.25) as fixed effects. Uterine blood flow included day and treatment x day (repeated measures). Dam BW was less (P ≤ 0.01) from d 223 of gestation through parturition for NR dams, but calf BW was not affected (P = 0.72) by treatment. The interaction affected (P &amp;lt; 0.01) heart rate, where NR dams had decreased heart rate after treatments began. Treatment did not affect (P ≥ 0.20) uterine artery blood flow or hemodynamics, but all variables were affected (P ≤ 0.04) by day. Contralateral total and cotyledonary weights tended (P ≤ 0.09) to be greater and ipsilateral and total cotyledonary:intercotyledonary ratios were greater (P ≤ 0.01) for CON. Cotyledon number, cotyledon size, and total cotyledonary, intercotyledonary, and placental weight were not affected (P ≥ 0.15) by treatment. Relative to dam BW, uterine blood flow was not affected (P = 0.83), but relative placental weight tended to be greater (P = 0.09) in NR dams. In the current study, NR dams lost maternal BW during late gestation and had less contralateral placental growth, yet uterine blood flow was maintained and placental size relative to BW ensured fetal growth similar to CON offspring.

PSX-A-16 Late-Breaking: Maternal nutrient restriction and re-alimentation influences liver protein expression in fetal sheep

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on the fetal liver proteome, 48 pregnant ewes with singletons were fed a control diet [100% National Research Council (NRC) requirements (CON)] starting at the beginning of gestation. On day 50 of gestation, a subset of ewes were fed either CON or 60% NRC requirements (RES). A subset of ewes were euthanized at day 90 of gestation (n = 7/treatment), and fetal liver samples collected. Remaining ewes were maintained on the current diet (CON-CON, n=6; RES-RES, n = 7) or switched to alternative diet (CON-RES, RES-CON; n=7/treatment). On day 130 of gestation, remaining ewes were euthanized, and fetal samples collected. Fetal liver proteins were extracted, digested by trypsin and subjected to multiplexed, label-based quantitative mass spectrometry analysis integrating Tandem Mass Tags. Proteins were identified and quantified using Proteome Discoverer (v2.5, Thermo Scientific) and differential abundance analysis was performed using ANOVA and post hoc Tukey’s HSD test. Hierarchal clustering analysis showed clustering of treatments by day of gestation. However, differences were also observed between treatments. At day 90 of gestation, 23 proteins were differentially expressed in RES compared with CON among which glycyl tRNA synthetase and pyruvate carboxylase were increased 12% and 10%, respectively (P &amp;lt; 0.03). At day 130 of gestation, 24, 5, and 71 proteins were differentially expressed in CON-RES, RES-CON, and RES-RES, respectively, compared with CON-CON. Carnosine dipeptidase 2 was decreased 7% in CON-RES and rho associated protein kinase and glycogen synthase 2 were increased 20% and 26% in RES-CON and RES-RES, respectively, compared with CON-CON (P &amp;lt; 0.04). These results indicate that nutrient restriction during mid- and late-gestation impacts expression of proteins involved in gluconeogenesis, glycogenesis, and the formation of carnosine, an integral molecule in beta-oxidation, and that re-alimentation alters proteins involved in cell migration pathways. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.

PSI-13 Effects of maternal nutrient restriction and melatonin supplementation on fetal mammary gland vascularity

Abstract The objective was to determine fetal mammary gland vascularity following dietary melatonin supplementation in late pregnant nutrient restricted Brangus heifers carrying female fetuses from two different seasons (spring calving, n = 12; fall calving, n = 13). Heifers were assigned one of four nutritional treatments at day 160 of gestation; adequate fed (ADQ-CON; 100% NRC; n = 6), nutrient restricted (RES-CON; 60% NRC; n = 6), adequate fed with 20 mg of melatonin (ADQ-MEL; n = 6), and nutrient restricted with 20 mg of melatonin (RES-MEL; n = 7). Fetal mammary glands were collected at day 240 of gestation following Cesarean delivery. Mammary gland vascularity was determined via immunofluorescence staining and analyzed via ANOVA. In spring calving heifers, maternal body weight was decreased (P = 0.002) in RES (528±11 kg) vs ADQ (601±11 kg) fed. Fetal body weight, fetal mammary gland weight, and mammary gland vascularity were not different (P &amp;gt; 0.15) among treatments. In fall calving heifers, a nutrition by treatment interaction (P = 0.048) was observed for maternal body weight, which was increased in ADQ-MEL versus all groups. Fetal body weight and fetal mammary gland weight were not different (P &amp;gt; 0.45) among groups. In fall calving, fetal mammary gland capillary number and average size were not different (P &amp;gt; 0.40) among groups. However, a nutrition by treatment interaction was observed for capillary area (P = 0.05), which was increased in RES-MEL versus ADQ-MEL. In addition, a nutrition by treatment interaction was observed for capillary perimeter (P = 0.001), which was increased in RES-MEL versus all groups. Overall, maternal nutrient restriction and melatonin supplementation did not impact fetal mammary gland vascularity in spring calving heifers; however, melatonin supplementation during nutrient restriction in fall calving heifers may increase fetal mammary gland vascularity. In conclusion, seasonal differences and natural melatonin production may influence melatonin-induced changes in fetal development.

248 Maternal Nutrient Restriction During Mid-gestation Decreases Uteroplacental Release and Fetal Uptake of Essential Amino Acids in Sheep

Abstract To examine the effects of maternal nutrient restriction on net uteroplacental flux during mid-gestation, 14 singleton ewes (48.2 ± 4.0 kg body weight) were fed 100% (control; CON; n = 7) or 60% of nutrient requirements (restricted; RES; n = 7) from day 50–90 (mid-gestation). On day 90, uteroplacental blood flow was measured via Doppler ultrasonography and blood samples were collected from the femoral artery, uterine vein, umbilical artery, and umbilical vein. Blood vessel glucose and amino acids (AA) concentrations were measured and arterial-venous (uterine, AV; fetal, va) differences and net fluxes were calculated. Data were analyzed using the GLM procedure of SAS for effects of treatment. Nutrient restriction during mid-gestation did not influence (P ≥ 0.17) uterine or umbilical blood flows. Uterine AV and fetal va differences of total, essential, and nonessential AA were not influenced (P &amp;gt; 0.10) by nutrient restriction. Nutrient restriction decreased (P ≤ 0.05) uterine and uteroplacental release of total AA and tended to decrease (P = 0.07) total AA uptake by the fetus. Uteroplacental release and fetal uptake of essential AA were decreased (P = 0.03) with RES by 53.4% and 45%, respectively. Uterine and uteroplacental release of nonessential AA were decreased (P = 0.03) with RES but, fetal uptake was not affected (P = 0.14). Nutrient restriction decreased (P ≤ 0.04) fetal uptake of methionine, phenylalanine, threonine, and valine and tended to decrease (P ≤ 0.10) fetal uptake of isoleucine, leucine, and tryptophan. Umbilical artery glucose concentrations were 32% lesser (P = 0.01) with RES and RES tended to increase (P = 0.08) fetal glucose uptake. Nutrient restriction during mid-gestation altered uteroplacental and fetal flux of AA in the current study. The results may indicate that fetal metabolism shifts to adapt to reduced AA supply which results in greater glucose utilization.

92 Maternal Nutrient Restriction of Primiparous Beef Heifers During Late Gestation Decreases Colostrum Yield and Reduces Calf Vigor

Abstract We hypothesized that late gestational nutrient restriction (NR) would reduce colostrum yield and impair offspring transition to postnatal life. Primiparous, fall-calving crossbred beef heifers (BW: 451 ± 28 [SD] kg; BCS: 5.4 ± 0.7) were individually-fed either 100% (control; CON; n = 12) or 70% (n = 13) of NASEM net energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to parturition. Delivery duration was determined as minutes from first fetal feet expulsion to birth. Calves were reared naturally by their dams and monitored for times from birth to first sternal recumbency, attempt to stand, and stand; vigor scores (1 = very weak, 5 = extremely vigorous) were assigned at 2, 5, 10, and 20 min of age. Total colostrum from one rear quarter was collected pre-suckling. Calf rectal temperatures were recorded at 0, 6, 12, 24, and 48 h postnatally. Data were analyzed with the fixed effects of treatment (single point) or treatment, hour, and their interaction (over time, using repeated measures). Date of calving was a fixed effect; calf sex was included when P &amp;lt; 0.25. Heifers fed CON had greater (P = 0.04) colostrum weight and volume than NR. Although gestational nutrition did not affect (P = 0.72) calf birth weight, calves born to CON heifers had faster (P = 0.02) times to stand and tended to have faster (P = 0.09) times to attempt to stand. Calves from CON heifers had greater (P = 0.05) 20 min vigor scores. Rectal temperatures at 0 h were greater (P = 0.02) in CON calves, but at 24 h were greater (P = 0.04) in NR calves. These data indicate that heifers nutrient restricted during late gestation have reduced colostrum yield and less vigorous calves, which may influence postnatal calf survival.

342 Effects of Maternal Nutrient Restriction During Late Gestation on Primiparous Dam Performance and Fetal Growth

Abstract To determine the effects of late gestational nutrient restriction (NR) on heifer performance, fetal growth, and calving difficulty, single-sired fall-calving Hereford-SimAngus heifers (BW: 451 ± 28 [SD] kg; BCS: 5.4 ± 0.7) bred to a single sire were allocated by fetal sex and expected calving date to either 100% (control; CON; n = 12) or 70% (n = 13) of NASEM net energy and metabolizable protein requirements for maintenance, pregnancy, and growth. Beginning on d 160 of gestation, heifers were individually fed chopped sorghum sudan hay (1.74 Mcal ME, 6.66% CP, 72.0% NDF; DM basis) and based on individual intakes, supplemented to meet targeted nutritional planes. Dam BW, BCS, and backfat (BF) were determined pre-treatment, every 21 d (BW) or 42 d (BCS and BF) during treatments, and post-calving. At birth, calf BW and size (length, heart girth, abdominal girth, flank girth, cannon circumference, cannon length, shoulder height, and ribeye area) were measured. Data were analyzed with treatment, treatment initiation date, and calf sex (when P &amp;lt; 0.25) as fixed effects. Dam BW tended to be less (P = 0.09) and BCS was less (P = 0.04) at d 202 of gestation for NR dams. Dam BW, BCS, and BF were less (P ≤ 0.01) in NR dams for the remainder of gestation. Post-calving, NR dams weighed 64 kg less (P ≤ 0.01) than CON, with a BCS of 3.6 ± 0.1. Nutrient restriction did not affect (P ≥ 0.27) calf gestation length, BW, or size. Calf BW as % post-calving dam BW tended to be greater (P = 0.09) for NR calves. Fetal presentation was normal for all CON births, while 23.1% of NR dams had fetal malpresentation (P = 0.12). In the current study, NR dam BW and BCS were sacrificed during late gestation without altering fetal growth trajectory.

PSI-14 Effects of maternal nutrient restriction during late gestation on neonatal beef calf serum chemistry and complete blood cell count

Abstract To determine effects of late gestational nutrient restriction (NR) on neonatal blood chemistry and hematology, primiparous fall-calving crossbred beef heifers [BW: 451 ± 28 (SD) kg; BCS: 5.4 ± 0.7] were individually fed either 100% (control; CON; n = 12) or 70% (n = 13) of NASEM net energy and metabolizable protein requirements for maintenance, pregnancy, and growth from d 160 of gestation to parturition. Calf jugular blood was obtained at 0 (pre-suckling), 6, 12, 24, and 48 h postnatally to determine serum chemistry and complete blood cell count. Data were analyzed with fixed effects of treatment, hour, and their interaction, using repeated measures. Calving date was a fixed effect; calf sex was included when P &amp;lt; 0.25. The treatment x hour interaction (P &amp;lt; 0.10) affected total protein, globulin, gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST), creatinine, creatine kinase, red blood cells (RBC), hemoglobin, hematocrit, sodium, anion gap, and potassium. Total protein and globulin at 6 to 48 h were greater (P ≤ 0.02) in NR calves. Calves from NR heifers had greater (P &amp;lt; 0.08) GGT at 6, 12, and 48 h and greater (P ≤ 0.07) AST at 0 to 24 h. Creatinine at 24 h and creatine kinase at 6 to 24 h were greater (P &amp;lt; 0.04) in NR calves. Hematocrit from 6 to 24 h and RBC and hemoglobin at 6 and 12 h were greater (P ≤ 0.09) in CON calves. Sodium from 0 to 48 h and anion gap at 6 h were greater (P &amp;lt; 0.09) in CON calves. Calves from NR heifers had greater (P = 0.03) 0 h potassium. Treatment affected chloride, which was greater (P = 0.08) in CON calves. These data indicate calves born to nutrient restricted heifers may experience more trauma at calving but have improved passive transfer.

Breastfeeding undernutrition changes iBAT-involved thermogenesis protein expression and leads to a lean phenotype in adult rat offspring

Nutritional insults early in life have been associated with metabolic diseases in adulthood. We aimed to evaluate the effects of maternal food restriction during the suckling period on metabolism and interscapular brown adipose tissue (iBAT) thermogenically involved proteins in adult rat offspring. Wistar rats underwent food restriction by 50% during the first two-thirds of lactation (FR50 group). Control rats were fed ad libitum throughout lactation (CONT group). At birth, the litter size was adjusted to eight pups, and weaning was performed at 22 days old. Body weight and food and water intake were assessed every two days. High- (HCD, 4,589 cal) and normal-caloric diet (NCD, 3,860 cal) preferences, as well as food intake during the dark part of the cycle, were assessed. At 100 days old, the rats were euthanized, and blood and tissues were removed for further analyses. Adult FR50 rats, although hyperphagic and preferring to eat HCD (P<.001), were leaner (P<.001) than the CONT group. The FR50 rats, were normoglycemic (P=.962) and had hypertriglyceridemia (P<.01). In addition, the FR50 rats were dyslipidemic (P<.01), presenting with a high atherogenic risk by the Castelli indexes (P<.01), had a higher iBAT mass (P<.01), fewer β3 adrenergic receptors (β3-AR, P<.05) and higher iBAT expression of uncoupled protein 1 (UCP1, P<.05) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α, P<.001) than the CONT rats. In conclusion, maternal food restriction during early breastfeeding programs rat offspring to have a lean phenotype, despite hyperphagia, and increased iBAT UCP1 and PGC-1α protein expression.

Reduction of In Vivo Placental Amino Acid Transport Precedes the Development of Intrauterine Growth Restriction in the Non-Human Primate.

Intrauterine growth restriction (IUGR) is associated with reduced placental amino acid transport (AAT). However, it remains to be established if changes in AAT contribute to restricted fetal growth. We hypothesized that reduced in vivo placental AAT precedes the development of IUGR in baboons with maternal nutrient restriction (MNR). Baboons were fed either a control (ad libitum) or MNR diet (70% of control diet) from gestational day (GD) 30. At GD 140, in vivo transplacental AA transport was measured by infusing nine (13)C- or (2)H-labeled essential amino acids (EAAs) as a bolus into the maternal circulation at cesarean section. A fetal vein-to-maternal artery mole percent excess ratio for each EAA was measured. Microvillous plasma membrane (MVM) system A and system L transport activity were determined. Fetal and placental weights were not significantly different between MNR and control. In vivo, the fetal vein-to-maternal artery mole percent excess ratio was significantly decreased for tryptophan in MNR. MVM system A and system L activity was markedly reduced in MNR. Reduction of in vivo placental amino acid transport precedes fetal growth restriction in the non-human primate, suggesting that reduced placental amino acid transfer may contribute to IUGR.

Mechanisms linking hypoxia to phosphorylation of insulin-like growth factor binding protein-1 in baboon fetuses with intrauterine growth restriction and in cell culture.

Hypoxia increases fetal hepatic insulin-like growth factor binding protein-1 (IGFBP-1) phosphorylation mediated by mechanistic target of rapamycin (mTOR) inhibition. Whether maternal nutrient restriction (MNR) causes fetal hypoxia remains unclear. We used fetal liver from a baboon (Papio sp.) model of intrauterine growth restriction due to MNR (70% global diet of Control) and liver hepatocellular carcinoma (HepG2) cells as a model for human fetal hepatocytes and tested the hypothesis that mTOR-mediated IGFBP-1 hyperphosphorylation in response to hypoxia requires hypoxia-inducible factor-1α (HIF-1α) and regulated in development and DNA-damage responses-1 (REDD-1) signaling. Western blotting (n=6) and immunohistochemistry (n=3) using fetal liver indicated greater expression of HIF-1α, REDD-1 as well as erythropoietin and its receptor, and vascular endothelial growth factor at GD120 (GD185 term) in MNR versus Control. Moreover, treatment of HepG2 cells with hypoxia (1% pO2 ) (n=3) induced REDD-1, inhibited mTOR complex-1 (mTORC1) activity and increased IGFBP-1 secretion/phosphorylation (Ser101/Ser119/Ser169). HIF-1α inhibition by echinomycin or small interfering RNA silencing prevented the hypoxia-mediated inhibition of mTORC1 and induction of IGFBP-1 secretion/phosphorylation. dimethyloxaloylglycine (DMOG) induced HIF-1α and also REDD-1 expression, inhibited mTORC1 and increased IGFBP-1 secretion/phosphorylation. Induction of HIF-1α (DMOG) and REDD-1 by Compound 3 inhibited mTORC1, increased IGFBP-1 secretion/ phosphorylation and protein kinase PKCα expression. Together, our data demonstrate that HIF-1α induction, increased REDD-1 expression and mTORC1 inhibition represent the mechanistic link between hypoxia and increased IGFBP-1 secretion/phosphorylation. We propose that maternal undernutrition limits fetal oxygen delivery, as demonstrated by increased fetal liver expression of hypoxia-responsive proteins in baboon MNR. These findings have important implications for our understanding of the pathophysiology of restricted fetal growth.