Maternal Nutrient Restriction Research Articles

Placental Transcriptome Adaptations to Maternal Nutrient Restriction in Sheep.

Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35–135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.

MO019MATERNAL UNDERNUTRITION AMELIORATES CYST GROWTH IN ADPKD MODEL MICE*

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive development of kidney and liver cysts. The major factors predicting disease progression in ADPKD are total kidney volume, genotype, age, sex. Recently, several studies have suggested that dietary intervention might be a potential treatment to prevent ADPKD progression. On the other hand, it has been reported that low-birth weight infants because of maternal global nutrient restriction are at increased risk for hypertension, type 2 diabetes, and metabolic syndrome and chronic kidney disease. However, little has been reported on relationship between maternal undernutrition and cyst formation in ADPKD. Therefore the purpose of this study is to clarify whether maternal undernutrition is associated with progression in ADPKD. Method We used Pkd1 conditional knockout mice (Pkd1flox/flox･Mx1-Cre mice). The offspring of dams given food ad libitum (control(CON)) and those subjected to nutrient restriction throughout pregnancy (food restriction (FR)) were examined. In FR, nutrient-restricted mothers were given about half amount of food by control mice during pregnancy. After delivery, food for children was given ad libitum. Mice were injected with polyinosinic-polycytidylic acid for 6 consecutive days from postnatal day 5 (P5) to P10 to inactivate Pkd1. We analyzed the phenotype of cystic kidneys by kidney/body weight ratio (2KW/BW), and cystic index (CI) which was defined as the percentage of areas occupied by cysts at P20, 35, 56. We carried out a series of analyses by kidney/body weight ratio, liver /body weight ratio or cystic index (CI) which was defined as the percentage of areas occupied by cysts. Elastica-Masson staining was performed for analyzing tissue fibrosis. The fibrotic index (FI) was expressed as the (fibrotic area/ total non-cystic area) ×100 (%). For evaluation of glomerular hypertrophy, glomerular area was measured in PAS-stained kidney sections using Image J software. The assay of renal function was performed by using UN-ML kit. We also performed western blotting of signaling pathway of proliferation by using whole kidneys. Data are shown as mean ± SEM. Two-tailed Student’s t-test was performed for comparing two groups. Results Food restriction of pregnant dams reduced birth weight. (FR 1.26±0.16 g vs CON 1.55±0.11g). However, FR showed rapid gain weight. There was no significant difference after P20. There were no difference between two groups in 2KW/BW, serum blood urea nitrogen (BUN) levels, CI of kidney and liver until P35. At P56, 2KW/BW was significantly greater in FR (4.59±0.52%) than in CON mice (2.91±0.98%; p＜0.01). CI of both kidney and liver was significantly higher in FR than in CON (Kidney : FR58.1±2.04% vs CON46.3±3.04%; p＜0.05) (Liver : FR11.1±1.41% vs CON 4.89±0.61%; p＜0.001). BUN levels elevated in FR (FR 58.1±5.76mg/dL vs CON 46.3±5.11mg/dL; p＜0.05) .FR showed glomerular sclerosis with PAS staining. Mean Glomerular volume was significantly increased in FR compared with CON (P35: FR 5625±419μm2 vs CON 3255±433μm2; p＜0.001, P56: FR 5780±1195μm2 vs CON 3756±266μm2; p＜0.001) . FR group showed significantly greater fibrosis in kidney (P35: FI 15.3±2.04% vs CON 11.1±1.41%; p＜0.01,P56: FI 42.1±3.2% vs CON 30.8±3.89%; p＜0.001). In western blotting analysis, MAPK pathway and mTOR pathway were suppressed in FR compared with CON at P20. In contrast, MAPK pathway and mTOR pathway were upregulated in FR compared with CON at P56. Conclusion Maternal undernutrition accelerates disease progression via kidney fibrosis, MAPK and mTOR pathway.

Liver Proteome Profile of Growth Restricted and Appropriately Grown Newborn Wistar Rats Associated With Maternal Undernutrition.

BackgroundFetal growth restriction (FGR) has been associated with adverse perinatal outcomes and epigenetic modifications that impact gene expression leading to permanent changes of fetal metabolic pathways and thereby influence development of disease in childhood and adult life. In this study, we investigated the result of maternal food restriction on liver protein expression in Wistar male newborn pups.Materials & MethodsTen (n = 10) timed pregnant Wistar rats on their 14th day of gestation were randomly assigned to either control (n = 4) or food restricted group (n = 6). The control group had ad libitum access to food. In the food restricted group, maternal diet was limited in a moderate fashion (50%) from day 15 of pregnancy until delivery. All rats delivered spontaneously on day 21 and newborn pups were immediately weighed. Pups born to normally nourished mothers were considered as controls, while pups born to food restricted mothers were subdivided into two groups, based on their birth weight: growth restricted (FGR) and appropriately grown (non-FGR). Rats were euthanized immediately after birth and liver tissues of 11 randomly selected male offspring (FGR n = 4, non-FGR n = 4, control n = 3) were collected and analyzed using quantitative proteomics.ResultsIn total 6,665 proteins were profiled. Of these, 451 and 751 were differentially expressed in FGR and non-FGR vs. control, respectively, whereas 229 proteins were commonly expressed. Bioinformatics analysis of the differentially expressed proteins (DEPs) in FGR vs. control revealed induction of the super-pathway of cholesterol biosynthesis and inhibition of thyroid hormone metabolism, fatty acid beta oxidation and apelin liver signaling pathway. Analysis of DEPs in non-FGR vs. control groups showed inhibition of thyroid hormone metabolism, fatty acid beta oxidation, and apelin liver signaling pathway.ConclusionThis study demonstrates the impact of prenatal food restriction on the proteomic liver profile of FGR and non-FGR offspring underlying the importance of both prenatal adversities and birth weight on liver-dependent postnatal disease.

Effect of electro-acupuncture at ST 36 on maternal food restriction-induced lung phenotype in rat offspring.

Maternal food restriction (MFR) during pregnancy leads to pulmonary dysplasia in the newborn period and increases susceptibility to diseases, such as asthma and chronic lung disease, later in life. Previous studies have shown that maternal electro-acupuncture (EA) applied to "Zusanli" (ST 36) could prevent the abnormal expression of key lung developmental signaling pathways and improve the lung morphology and function in perinatal nicotine exposed offspring. There is a significant overlap in lung developmental signaling pathways affected by perinatal nicotine exposure and MFR during pregnancy; however, whether maternal EA at ST 36 also blocks the MFR-induced lung phenotype is unknown. Here, we examined the effects of EA applied to maternal ST 36 on lung morphology and function and the expression of key lung developmental signaling pathways, and the hypercorticoid state associated with MFR during pregnancy. These effects were compared with those of metyrapone, an intervention known to block MFR-induced offspring hypercorticoid state and the resultant pulmonary pathology. Like metyrapone, maternal EA at ST 36 blocked the MFR-induced changes in key developmental signaling pathways and protected the MFR-induced changes in lung morphology and function. These results offer a novel and safe, nonpharmacologic approach to prevent MFR-induced pulmonary dysplasia in offspring.

Melatonin-induced Changes in the Bovine Vaginal Microbiota During Maternal Nutrient Restriction in Brangus Heifers

Abstract Altering the composition of the bovine vaginal microbiota has proved challenging; with recent studies deeming the microbiota dynamic due to few overall changes being found. Therefore, the objectives of this study were to determine if gestational age, endogenous progesterone, maternal nutrient restriction, or dietary melatonin altered the composition of the bovine vaginal microbiota. Brangus heifers (n = 29) from timed artificial insemination to d 240 of gestation were used; at d 160 of gestation, heifers were assigned to either an adequate (ADQ; n = 14; 100% NRC requirements) or restricted (RES; n = 15; 60% NRC requirements) nutritional plane and were either supplemented with dietary melatonin (MEL; n = 15) or not supplemented (CON; n = 14). Samples for vaginal microbiota analysis were taken on d 0 (prior to artificial insemination), d 150 (prior to dietary treatments), and d 220 of gestation (60 days post-treatment initiation) using a double guarded culture swab. The vaginal bacterial community composition was determined through sequencing the V4 region of the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via two-way ANOVA; beta diversity was compared via PERMANOVA. The linear discriminant analysis for effect size (LEfSe) pipeline was utilized for analysis of taxonomic rank differences between bacterial communities. Gestational age, progesterone concentration, and maternal nutritional plane did not alter alpha or beta diversity of the vaginal microbiota. However, gestational age resulted in compositional changes at the order, family, and genus level. Moreover, dietary melatonin supplementation did not alter alpha diversity of the vaginal microbiota but did alter beta diversity (P = 0.02). Specifically, melatonin altered the composition at the genus level and increased the prevalence of aerobic bacteria in the vaginal tract. To date, melatonin is the first hormone associated with altering the composition of the vaginal microbiota.

Effects of Maternal Nutrient Restriction During Gestation on LH Production in the Female Bovine Fetus

Abstract Gestational nutrient restriction causes epigenetic and phenotypic changes that affect multiple physiological processes in the offspring. Gonadotropes, the cells in the anterior pituitary that secrete luteinizing hormone (LH) and follicle-stimulating hormone (FSH), are particularly sensitive to nutritional changes during fetal development. Our objective herein was to investigate the effects of gestational nutrient restriction on LH protein content and number of gonadotropes in the fetal bovine pituitary. We hypothesized that moderate nutrient restriction during mid to late gestation decreases pituitary LH production, which is associated with a reduced number of gonadotropes. Embryos were produced in vitro with X-bearing semen from a single sire then split to generate monozygotic twins. Each identical twin was transferred to a virgin dam yielding four sets of female twins. At gestational d 158, the dams were randomly assigned into two groups, one fed 100% NRC requirements (control) and the other fed 70% of NRC requirements (restricted) during the last trimester of gestation, ensuring each pair of twins had one twin in each group. At gestational d 265, the fetuses (n = 4/group) were euthanized by barbiturate overdose, and the pituitaries were collected. Western blots were performed using an ovine LH-specific antibody (Dr. A.F. Parlow, NIDDK). The total LH protein content in the pituitary tended to be decreased in the restricted fetuses compared to controls (P < 0.10). However, immunohistochemistry analysis of the pituitary did not reveal any significant changes in the total number of LH-positive cells (control = 460±23 cells/0.5 mm2; restricted = 496±45 cells/0.5 mm2, P = 0.58). In conclusion, while maternal nutrient restriction during gestation resulted in a trend of reduced LH content in the fetal pituitary, immunohistological findings suggest that these changes are likely related to the individual potential of each gonadotrope to produce LH, rather than alterations in cell differentiation during fetal development.

Maternal nutrient restriction alters thyroid hormone dynamics in placentae of sheep having small for gestational age fetuses

Thyroid hormones regulate a multitude of metabolic and cellular processes involved in placental and fetal growth, while maternal nutrient restriction (NR) has the potential to influence these processes. Those fetuses most impacted by NR, as categorized by weight, are termed small for gestational age (SGA), but the role of thyroid hormones in these pregnancies is not fully understood. Therefore, the aims of the present study were to determine effects of NR during pregnancy on maternal and fetal thyroid hormone concentrations, as well as temporal and cell-specific expression of mRNAs and proteins for placental thyroid hormone transporters, thyroid hormone receptors, and deiodinases in ewes having either SGA or normal weight fetuses. Ewes with singleton pregnancies were fed either a 100% NRC (n = 8) or 50% NRC (NR; n = 28) diet from Days 35 to 135 of pregnancy with a single placentome surgically collected on Day 70. Fetal weight at necropsy on Day 135 was used to designate the fetuses as NR NonSGA (n = 7; heaviest NR fetuses) or NR SGA (n = 7; lightest NR fetuses). Thyroid hormone levels were lower in NR SGA compared to NR NonSGA ewes, while all NR fetuses had lower concentrations of thyroxine at Day 135. Expression of mRNAs for thyroid hormone transporters SLC16A2, SLC16A10, SLCO1C1, and SLCO4A1 were altered by day, but not nutrient restriction. Expression of THRA mRNA and protein was dysregulated in NR SGA fetuses with protein localized to syncytial and stromal cells in placentomes in all groups. The ratio of deiodinases DIO2 and DIO3 was greater for NR SGA placentae at Day 70, while DIO3 protein was less abundant in placentae from NR SGA than 100% NRC ewes. These results identify mid-gestational modifications in thyroid hormone-associated proteins in placentomes of ewes having SGA fetuses, as well as a potential for placentomes from NonSGA pregnancies to adapt to, and overcome, nutritional restrictions during pregnancy.

Caspase-3 regulates ureteric branching in mice via cell migration

Inhibition of caspase-3 (Casp3) reduces ureteric branching in organ culture but the mechanism remains unclear. Since Casp3 has non-apoptotic functions, we examined whether Casp3 regulates ureteric branching by promoting cell migration, using a ureteric bud (UB) cell line and Casp3-deficient (Casp3−/−) mice. Also, we examined whether Casp3 plays a role in the reduced ureteric branching of metanephroi from nutrient restricted mothers, in which Casp3 activity is suppressed. A Casp3 inhibitor Ac-DNLD-CHO reduced FGF2-induced cord formation of UB cells in 3D culture. UB cell migration assessed by Boyden chamber and wound healing assays was inhibited by Ac-DNLD-CHO. Glomerular number was reduced by ≈ 30%, and ureteric tip number was lower in Casp3−/− mice compared with controls. Maternal nutrient restriction decreased ureteric tip number in controls but not in Casp3−/−. In conclusion, Casp3 regulates ureteric branching by promoting UB cell migration. Inhibited ureteric branching by maternal nutrient restriction may be mediated by Casp3.

Effect of electroacupuncture on lung dysplasia in rats with intrauterine growth restriction induced by maternal food restriction

To investigate the protective effect of electroacupuncture (EA) at "Zusanli" (ST 36) in pregnant rats on lung dysplasia of newborn rats with intrauterine growth restriction (IUGR) induced by maternal food restriction. Twenty-four female SD rats were randomly divided into a control group, a control+EA group, a model group and a model+EA group, 6 rats in each group. From the 10th day into pregnancy to the time of delivery, the rats in the model group and the model+EA group were given with 50% dietary restriction to prepare IUGR model. From the 10th day into pregnancy to the time of delivery, the rats in the control+EA group and the model+EA group were treated with EA at bilateral "Zusanli" (ST 36), once a day. The body weight of offspring rats was measured at birth, and the body weight and lung weight of offspring rats were measured on the 21st day after birth. The lung function was measured by small animal lung function detection system; the lung tissue morphology was observed by HE staining; the content of peroxisome proliferator activated receptor γ (PPARγ) in lung tissue was detected by ELISA. Compared with the control group, the body weight at birth as well as the body weight, lung weight, lung dynamic compliance (Cdyn) and PPARγ at 21 days after birth in the model group were significantly decreased (P<0.01), and the peak inspiratory flow (PIF) and inspiratory resistance (RI) were significantly increased (P<0.01); the number of alveoli was significantly decreased, and the alveolar area and alveolar septal thickness were significantly increased, and some alveoli were ruptured and fused. Compared with the model group, the body weight at birth as well as the body weight, lung weight, Cdyn and PPARγ at 21 days after birth in the model+EA group were significantly increased (P<0.01, P<0.05), and the PIF and RI were significantly reduced (P<0.05); the number of alveoli was significantly increased, and the alveolar area and alveolar septal thickness were significantly reduced, and the rupture and fusion of alveolar was improved. EA at "Zusanli" (ST 36) may protect the lung function and lung histomorphology changes by regulating the level of PPARγ of lung in IUGR rats induced by maternal food restriction.

Maternal nutrient restriction in late pregnancy programs postnatal metabolism and pituitary development in beef heifers

Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. Therefore, an experiment was conducted to evaluate postnatal growth, metabolism, and development of beef heifers exposed to late gestation maternal nutrient restriction. Pregnancies were generated via transfer of in vitro embryos produced using X-bearing sperm from a single Angus sire. Pregnant dams were randomly assigned to receive either 100% (control; n = 9) or 70% (restricted; n = 9) of their total energy requirements from gestational day 158 to parturition. From post-natal day (PND) 301 until slaughter (PND485), heifers were individually fed ad libitum in a Calan gate facility. Calves from restricted dams were lighter than controls at birth (P<0.05) through PND70 (P<0.05) with no difference in body weight from PND105 through PND485 (P>0.10). To assess pancreatic function, glucose tolerance tests were performed on PND315 and PND482 and a diet effect was seen with glucose area under the curve being greater (P<0.05) in calves born to restricted dams compared to controls. At slaughter, total internal fat was greater (P<0.05) in heifers born to restricted dams, while whole pituitary weight was lighter (P<0.05). Heifers from restricted dams had fewer growth hormone-positive cells (somatotrophs) compared to controls (P<0.05). Results demonstrate an impaired ability to clear peripheral glucose in heifers born to restricted dams leading to increased deposition of internal fat. A reduction in the number of somatotrophs may contribute to the adipogenic phenotype of heifers born to restricted dams due to growth hormone’s known anabolic roles in growth, lipolysis, and pancreatic islet function.

Melatonin-induced changes in the bovine vaginal microbiota during maternal nutrient restriction.

Altering the composition of the bovine vaginal microbiota has proved challenging, with recent studies deeming the microbiota dynamic due to few overall changes being found. Therefore, the objectives of this study were to determine whether gestational age, endogenous progesterone, maternal nutrient restriction, or dietary melatonin altered the composition of the bovine vaginal microbiota. Brangus heifers (n = 29) from timed artificial insemination to day 240 of gestation were used; at day 160 of gestation, heifers were assigned to either an adequate (ADQ; n = 14; 100% NRC requirements) or restricted (RES; n = 15; 60% NRC requirements) nutritional plane and were either supplemented with dietary melatonin (MEL; n = 15) or not supplemented (CON; n = 14). Samples for vaginal microbiota analysis were taken on day 0 (prior to artificial insemination), day 150 (prior to dietary treatments), and day 220 of gestation (60 d post-treatment initiation) using a double guarded culture swab. The vaginal bacterial overall community structure was determined through sequencing the V4 region of the 16S rRNA gene using the Illumina Miseq platform. Alpha diversity was compared via 2-way ANOVA; β diversity was compared via PERMANOVA. The linear discriminant analysis for effect size (LEfSe) pipeline was utilized for analysis of taxonomic rank differences between bacterial communities. Gestational age, progesterone concentration, and maternal nutritional plane did not alter α or β diversity of the vaginal microbiota. However, gestational age resulted in compositional changes at the order, family, and genus level. Moreover, dietary melatonin supplementation did not alter α diversity of the vaginal microbiota but did alter β diversity (P = 0.02). Specifically, melatonin altered the composition at the genus level and increased the prevalence of aerobic bacteria in the vaginal tract. To date, melatonin is the first hormone associated with altering the composition of the bovine vaginal microbiota.

The Influence of Maternal Dietary Intake During Mid-Gestation on Growth, Feedlot Performance, miRNA and mRNA Expression, and Carcass and Meat Quality of Resultant Offspring

This research analyzed how maternal plane of nutrition during mid-gestation impacts growth, blood metabolites, expression of microRNA and messenger RNA in skeletal muscle, feedlot performance, and carcass characteristics of progeny. Thirty-two cows were bred to the same Angus sire and fed to either maintain a body condition score (BCS) of 5.0 to 5.5 (maintenance [MAIN]; n = 15) or to lose 1 BCS (restriction [REST]; n = 17) over an 84-d period of mid-gestation. Following the second trimester, all cows were co-mingled and fed at maintenance for the remainder of gestation. Following the 84-d treatment period, REST cows had a lower (P &amp;lt; 0.01) BCS than MAIN cows. At the end of the third trimester, there was no difference (P = 0.78) in BCS between the treatment groups. There was no difference (P &amp;gt; 0.10) between offspring in birthweight, weaning weight, average daily gain, feed efficiency, dry matter intake, carcass yield, steak quality, or in circulating levels of glucose, cortisol, insulin, or insulin-like growth factor-1. REST offspring expressed more (P &amp;lt; 0.05) miR-133a, miR-133b, miR-181d, miR-214, miR-424 and miR-486 at weaning than MAIN offspring. At harvest, REST offspring expressed more (P &amp;lt; 0.05) miR-133a and less (P &amp;lt; 0.01) miR-486 than MAIN offspring. REST steaks were perceived as more tender (P = 0.05) by a trained sensory panel. These results indicate that maternal nutrient restriction during mid-gestation resulting in a loss of 1 BCS has an effect on microRNA expression in the skeletal muscle but does not alter postnatal growth potential, carcass quality, or end product quality of the offspring. This suggests that moderate restriction in maternal nutrition during the second trimester, which results in a drop in BCS that can be recovered during the third trimester, should not cause alarm for producers when considering future offspring performance.

Cerebrum, liver, and muscle regulatory networks uncover maternal nutrition effects in developmental programming of beef cattle during early pregnancy

The molecular basis underlying fetal programming in response to maternal nutrition remains unclear. Herein, we investigated the regulatory relationships between genes in fetal cerebrum, liver, and muscle tissues to shed light on the putative mechanisms that underlie the effects of early maternal nutrient restriction on bovine developmental programming. To this end, cerebrum, liver, and muscle gene expression were measured with RNA-Seq in 14 fetuses collected on day 50 of gestation from dams fed a diet initiated at breeding to either achieve 60% (RES, n = 7) or 100% (CON, n = 7) of energy requirements. To build a tissue-to-tissue gene network, we prioritized tissue-specific genes, transcription factors, and differentially expressed genes. Furthermore, we built condition-specific networks to identify differentially co-expressed or connected genes. Nutrient restriction led to differential tissue regulation between the treatments. Myogenic factors differentially regulated by ZBTB33 and ZNF131 may negatively affect myogenesis. Additionally, nutrient-sensing pathways, such as mTOR and PI3K/Akt, were affected by gene expression changes in response to nutrient restriction. By unveiling the network properties, we identified major regulators driving gene expression. However, further research is still needed to determine the impact of early maternal nutrition and strategic supplementation on pre- and post-natal performance.

Impact of Maternal Food Restriction on Heart Proteome in Appropriately Grown and Growth-Restricted Wistar-Rat Offspring.

Objective: Fetal growth restriction is associated with increased postnatal cardiovascular morbidity. The alterations in heart physiology and structure caused by in utero nutrient deprivation have not been extensively studied. We aim to investigate the impact of maternal food restriction on the cardiac proteome of newborn rats with normal (non-fetal growth-restricted (FGR)) and reduced (FGR) birth weight. Methods: On day 14 of gestation, 10 timed pregnant rats were randomized into two nutritional groups: (a) Standard laboratory diet and (b) 50% global food restriction. Pups born to food-restricted mothers were subdivided, based on birthweight, into fetal growth-restricted (FGR) and non-FGR, while pups born from normally nourished mothers were considered controls. Rat neonates were euthanized immediately after birth and the hearts of 11 randomly selected male offspring (n = 4 FGR, n = 4 non-FGR, n = 3 control group) were analyzed using quantitative proteomics. Results: In total, 7422 proteins were quantified (q < 0.05). Of these, 1175 were differentially expressed in FGR and 231 in non-FGR offspring vs. control with 151 common differentially expressed proteins (DEPs) between the two groups. Bioinformatics analysis of DEPs in FGR vs. control showed decreased integrin and apelin cardiac fibroblast signaling, decreased muscle contraction and glycolysis, and over-representation of a protein network related to embryonic development, and cell death and survival. Conclusion: Our study illustrates the distinct proteomic profile of FGR and non-FGR offspring of food-restricted dams underlying the importance of both prenatal adversities and birth weight in cardiac physiology and development.

Gestation Food Restriction and Refeeding Compensate Maternal Energy Status and Alleviate Metabolic Consequences in Juvenile Offspring in a Rabbit Model.

Nutritional status during gestation can influence mother and offspring metabolism. Undernutrition in pregnancy affects women in both western and developing countries, and it is associated with a high prevalence of chronic diseases in later life. The present work was conducted in the rabbit model, as a longitudinal study, to examine the effect of food restriction during early and mid-gestation, and re-feeding ad libitum until the end of pregnancy on metabolic status and body reserves of mother and, its association with development and metabolism of fetuses and female offspring to the juvenile stage. Little changes in live body weight (LBW), compensatory feed intake, similar body reserves, and metabolism were observed in dams. Placenta biometry and efficiency were slightly affected, but fetal BW and phenotype were not modified. However, hyperinsulinemia, insulin resistance, and hypertriglyceridemia were demonstrated in pre-term fetuses. In the juvenile period, these changes were not evidenced, and a similar pattern of growth and serum metabolic parameters in offspring of food-restricted mothers were found, except in serum aminotransferases levels, which increased. These were associated with higher liver fibrosis. Maternal food restriction in the early and mid-pregnancy followed by re-feeding in our rabbit model established a compensatory energy status in dams and alleviated potential long-term consequences in growth and metabolism in the offspring, even if fetal metabolism was altered.

Effects of maternal nutrient restriction during the periconceptional period on placental development in the mouse.

Maternal undernutrition has detrimental effects on fetal development and adult health. Total caloric restriction during early pregnancy followed by adequate nutrition for the remainder of gestation, is particularly linked to cardiovascular and metabolic disease risks during adulthood. The placenta is responsible for transport of nutrients from the maternal to fetal circulation, and the efficiency with which it does so can be adjusted to the maternal nutrient supply. There is evidence that placental adaptations to nutrient restriction in early pregnancy may be retained even when adequate nutrition is restored later in pregnancy, leading to a potential mismatch between placental efficiency and maternal nutrient supplies. However, in the mouse, 50% caloric restriction from days 1.5–11.5 of gestation, while temporarily altering placental structure and gene expression, had no significant effect on day 18.5. The periconceptional period, during which oocyte maturation, fertilization, and preimplantation development occur may be especially critical in creating lasting impact on the placenta. Here, mice were subjected to 50% caloric restriction from 3 weeks prior to pregnancy through d11.5, and then placental structure, the expression of key nutrient transporters, and global DNA methylation levels were examined at gestation d18.5. Prior exposure to caloric restriction increased maternal blood space area, but decreased expression of the key System A amino acid transporter Slc38a4 at d18.5. Neither placental and fetal weights, nor placental DNA methylation levels were affected. Thus, total caloric restriction beginning in the periconceptional period does have a lasting impact on placental development in the mouse, but without changing placental efficiency.

Maternal self-efficacy is associated with mother-child feeding practices in middle childhood

ObjectiveMaternal self-efficacy (MSE) is a well-established correlate of health outcomes in young children, though little is known about this association in older children. The purpose of this cross-sectional study was to examine how MSE relates to mother-child feeding practices in middle childhood. MethodsA total of 306 children ages 8–12 (Mean age = 9.72, SD = 0.91, 52.9% female) and their mothers participated in this study. Mothers completed the New General Self-Efficacy Scale and the Child Feeding Questionnaire. A series of hierarchical regression models were used to examine how MSE related to maternal food restriction, maternal pressure to eat, and maternal food monitoring. ResultsAfter accounting for maternal Body Mass Index (BMI), education, and age, and child Body Mass Index Percentile (BMI%ile) and age within the first step of each regression model, MSE emerged as a significant predictor for maternal restriction of foods (p = .024) and maternal food monitoring (p = .048). MSE was not significantly related to maternal pressure to eat. ConclusionsThis study is the first to establish that higher MSE is significantly related to healthier mother-child feeding practices in middle childhood, providing preliminary justification for enhancing MSE within comprehensive family interventions to support child weight-related health.

Maternal undernutrition modulates hepatic MicroRNAs expression in the early life of offspring

Emerging studies revealed that a poor intrauterine environment elicited by maternal nutrient restriction (MNR) is associated with an increased risk of metabolic diseases in adulthood. Previous research has shown that microRNAs (miRNAs) exert pivotal roles in modulating molecular pathways involved in disease pathogenesis and progression. In this respect, we herein examined miRNA profiles in samples of liver from offspring whose mothers were fed either with a 50% food-restricted diet or standard laboratory chow during pregnancy. Our findings enumerated that miR-181a, involved in lipid metabolism, was found to be downregulated in the liver of MNR offspring at 1 day of age when compared to that of control offspring. We also noted that overexpression of miR-181a reduced the lipid droplets after treatment with oleic acid for 48 h, which suppressed the expressions levels of SIRT1, FOXO1, KLF6 and PPARγ in BRL-3A cells, while the opposite results were observed with decreased expression of miR-181a. Furthermore, the luciferase reporter assay confirmed the direct interactions between miR-181a with KLF6 and SIRT1. In adults, the MNR offspring elucidated increased TG content, decreased expression of miR-181a, and increased expressions levels of SIRT1, FOXO1, KLF6, and PPARγ in liver tissues. Collectively, these findings provided novel evidence that MNR could regulate miRNAs expression, which might be related to lipid metabolism in MNR offspring.

219 Effects of maternal nutrient restriction and rumen-protected arginine supplementation on post-ruminal digestive enzyme activities of lamb offspring

Abstract To determine the effects of maternal nutrient restriction and rumen-protected arginine supplementation on post-ruminal digestive enzymes in lambs, 31 multiparous, Rambouillet ewes were allocated to one of three dietary treatments at 54 d of gestation. Dietary treatments were 100% of nutrient requirements (control, CON; n=11), 60% of control (restricted, RES; n=10), or RES plus a rumen-protected arginine supplement dosed at 180 mg/kg BW once daily (RES-ARG; n=10). At parturition, lambs were immediately removed from dams and reared independently. Milk-replacer and alfalfa hay + creep feed was offered for ad libitum intake. At day 54 of age, lambs were slaughtered and the pancreas and small intestine were collected. Pancreatic (α-amylase, trypsin) and small intestinal (maltase, glucoamylase, sucrase, isomaltase, lactase) digestive enzyme activities were assayed. Data were analyzed using the GLM procedure of SAS with treatment and fetal sex included in the model statement. Contrast statements were used to determine differences between means for effects of restriction (CON vs. RES and RES-ARG) and rumen-protected arginine supplementation (RES vs. RES-ARG). There was no influence (P≥0.32) of maternal nutrient restriction or rumen-protected arginine supplementation on pancreatic or small intestinal protein concentrations. No treatment effects were observed (P≥0.14) for enzymes involved in starch digestion including pancreatic α-amylase and small intestinal maltase, glucoamylase, and isomaltase. Sucrase activity was undetected in the small intestine of lambs across all treatments. Maternal nutrient restriction tended to increase (P=0.09) pancreatic trypsin specific activity in lambs. Lactase specific activity in the small intestine of lambs tended to decrease (P=0.08) with maternal nutrient restriction. Rumen-protected arginine supplementation to gestating ewes did not influence (P≥0.19) digestive enzyme activities of lamb offspring. These data suggest that maternal nutrient restriction may result in increased pancreatic trypsin activity of lambs to potentially compensate for inadequate pre-natal nutrient supply.

PSIV-16 Maternal Nutrient Restriction Followed by Re-alimentation Alters Distinct Metabolic Pathways in Sheep Offspring

Abstract To determine the effects of maternal nutrient restriction and re-alimentation on offspring metabolism, 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, muscle, and blood 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, longissimus dorsi, and blood metabolites were analyzed using LC-MS/MS at Metabolon Inc. Pathway enrichment analysis was conducted using MetaboAnalyst 4.0. In liver, muscle, and blood, 64, 44, and 34 pathways were enriched between treatments at day 130 gestation and 10, 6, and 11 pathways were enriched at day 90 gestation, respectively. Arginine and proline metabolism; primary bile acid biosynthesis; and valine, leucine, and isoleucine biosynthesis were the most highly enriched pathways in RES compared with CON in liver, muscle, and blood, respectively. Additionally, the pentose phosphate pathway; valine, leucine, and isoleucine metabolism; and phenylalanine metabolism were the most highly enriched pathways in RES-CON compared with CON-CON in liver, muscle, and blood, respectively. In liver, ribulose 5-phosphate, xylulose 5-phosphate, and ribose 5-phosphate were decreased 1.82-, 1.54-, and 2.38-fold, respectively in RES-CON compared with CON-CON (P ≤ 0.05). Total triacylglycerols were increased 3.04-fold in muscle and decreased 1.57-fold in blood in RES-CON and RES-RES compared with CON-CON and CON-RES (P ≤ 0.05). Mid-gestational nutrient restriction and subsequent re-alimentation altered distinct metabolic amino acid, carbohydrate, and lipid pathways, potentially altering postnatal growth. Supported by USDA-AFRI grants 2016-67016-24884 and 2017-67016-26568.