scholarly journals 345 The effects of maternal nutrient restriction followed by re-alimentation on offspring growth and metabolism in sheep

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 98-98
Author(s):  
Brandon I Smith ◽  
Manuel A Vásquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Kendall C Swanson ◽  
Anna T Grazul-Bilska ◽  
...  
Keyword(s):  
Maternal Nutrition ◽  
Management Practice ◽  
Fetal Liver ◽  
Control Diet ◽  
Liver Lipid ◽  
Nutrient Restriction ◽  
Triceps Brachii ◽  
Liver Growth ◽  
Offspring Growth ◽  
Negative Impacts

Abstract The duration and timing of inadequate maternal nutrition can have detrimental effects on metabolism and organogenesis in the offspring. Re-alimentation, a common management practice that involves feeding full nutrient requirements following a period of nutrient restriction, may reduce the negative impacts of maternal nutrient restriction. To determine the effects of maternal nutrient restriction and re-alimentation on offspring growth,48 primiparous ewes, confirmed pregnant with singletons, were fed a control diet consisting of100% NRC requirements (CON) starting on day25 of gestation. On day50 of gestation, ewes (n = 7) were euthanized and fetal liver, muscle, and blood samples were collected. The remaining animals were fed either CON or60% NRC requirements (RES). On day90 of gestation, a portion of ewes were euthanized (n = 7 per treatment) and fetal samples and weights were collected. Remaining ewes were maintained on the current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to the alternative diet (CON-RES, RES-CON; n = 7/treatment). On day130 of gestation, all remaining ewes were euthanized. All fetal BW, liver, longissimus muscle, semitendinosus, and triceps brachii weights were determined for each day of gestation. Fetal BW’s were not different between treatment groups (P = 0.29; P = 0.83). Fetal liver weights decreased12.89% in RES-RES compared with CON-CON at day130 (P = 0.049), but were not different at day90 (P = 0.69). There was a tendency for decreased semitendinosus weight in RES group compared with CON at day90 (P = 0.055). Liver lipid droplet accumulation was analyzed for day90 and130 using histochemistry and an effect of maternal nutrition was not observed (P = 0.562). In summary, maternal nutrient restriction reduces offspring muscle and liver growth. To gain insight into the effects of maternal nutrient restriction and re-alimentation on liver development and metabolism, analysis of liver morphology, gene expression, and global metabolomics are needed. Supported by USDA-AFRI grant2016-67016-24884

scholarly journals Maternal nutrition alters the expression of insulin-like growth factors in fetal sheep liver and skeletal muscle

2000 ◽  
Vol 167 (3) ◽  
pp. 429-437 ◽  
Author(s):  
JM Brameld ◽  
A Mostyn ◽  
J Dandrea ◽  
TJ Stephenson ◽  
JM Dawson ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Growth Hormone Receptor ◽  
Maternal Nutrition ◽  
Fetal Liver ◽  
Mrna Abundance ◽  
Nutrient Restriction ◽  
Fetal Sheep ◽  
Gestation Age ◽  
Igf I ◽  
Metabolisable Energy

We investigated the influence of maternal dietary restriction between days 28 and 80 of gestation followed by re-feeding to the intake of well-fed ewes up to 140 days of gestation (term is 147 days) in sheep, on expression of mRNA for insulin-like growth factor (IGF)-I, IGF-II and growth hormone receptor (GHR) in fetal liver and skeletal muscle. Singleton bearing ewes either consumed 3.2-3.8 MJ/day of metabolisable energy (ME) (i.e. nutrient restricted - approximately 60% of ME requirements, taking into account requirements for both ewe maintenance and growth of the conceptus) or 8.7-9.9 MJ/day (i.e. well fed - approximately 150% of ME requirements) between days 28 and 80 of gestation. All ewes were then well fed (150% of ME requirements) up to day 140 of gestation and consumed 8-10.9 MJ/day. At days 80 and 140 of gestation, five ewes were sampled from each group and fetal tissues taken. There was no difference in fetal body weight or liver weights between groups at either sampling date, or skeletal muscle (quadriceps) weight at 140 days. IGF-I mRNA abundance was lower in livers of nutrient-restricted fetuses at day 80 of gestation (nutrient restricted 2.35; well fed 3.70 arbitrary units), but was higher than well-fed fetuses at day 140 of gestation, after 60 days of re-feeding (restricted/re-fed 4.27; well fed 2.83;s.e.d. 0.98 arbitrary units, P=0.061 for dietxage interaction). IGF-II mRNA abundance was consistently higher in livers of nutrient-restricted fetuses (80 days: nutrient restricted 7.78; well fed 5.91; 140 days: restricted/re-fed 7.23; well fed 6.01;s.e.d. 1.09 arbitrary units, P=0.061 for diet). Nutrient restriction had no effect on hepatic GHR mRNA abundance, but re-feeding of previously nutrient-restricted fetuses increased GHR mRNA compared with continuously well-fed fetuses (80 days: nutrient restricted 70.6; well fed 75.1; 140 days: restricted/re-fed 115.7; well fed 89.4;s.e.d. 10.13 arbitrary units, P=0.047 for dietxage interaction). In fetal skeletal muscle, IGF-I mRNA abundance was not influenced by maternal nutrition and decreased with gestation age (P<0.01). IGF-II mRNA abundance was higher in skeletal muscle of nutrient-restricted fetuses compared with well-fed fetuses at day 80 of gestation (nutrient restricted 16.72; well fed 10.53 arbitrary units), but was lower than well-fed fetuses after 60 days of re-feeding (restricted/re-fed 7.77; well fed 13.72;s.e.d. 1.98 arbitrary units, P<0.001 for dietxage interaction). There was no effect of maternal nutrition or gestation age on fetal skeletal muscle GHR expression. In conclusion, maternal nutrient restriction in early to mid gestation with re-feeding thereafter results in alterations in hepatic and skeletal muscle expression of IGF-I, IGF-II and/or GHR in the fetus which may subsequently relate to altered organ and tissue function.

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

2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 307-307
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
Kendall C Swanson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lipid Content ◽  
Muscle Development ◽  
Glycogen Synthase ◽  
Fetal Liver ◽  
Control Diet ◽  
National Research Council ◽  
Pyruvate Dehydrogenase Kinase ◽  
Nutrient Restriction ◽  
Metabolic Factors

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 &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.

scholarly journals Impacts of maternal nutrition on uterine and placental vascularity and mRNA expression of angiogenic factors during the establishment of pregnancy in beef heifers1

2017 ◽  
Vol 1 (2) ◽  
pp. 160-167 ◽  
Author(s):  
K. J. McLean ◽  
M. S. Crouse ◽  
M. R. Crosswhite ◽  
N. Negrin Pereira ◽  
C. R. Dahlen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Maternal Nutrition ◽  
Control Diet ◽  
Uterine Horn ◽  
Angiogenic Factors ◽  
Angiogenic Factor ◽  
Nutrient Restriction ◽  
Beef Heifers ◽  
Vascular Volume

Abstract We hypothesized that maternal nutrient restriction starting at the time of breeding would influence placental vascular development and gene expression of angiogenic factors during the first 50 d of gestation in beef heifers. Commercial Angus crossbred heifers (n = 49) were maintained on a total mixed ration and supplemented with dried distillers grains with solubles. All heifers were subject to 5-d CO-Synch + CIDR estrous synchronization protocol, AI to a single Angus sire, and randomly assigned to dietary treatments. One half were assigned to control diet (CON) targeted to gain 0.45 kg/d and the remaining half were assigned to restricted diet (RES), which received 60% of CON. Heifers were subjected to ovariohysterectomy on d 16, 34, or 50 of gestation. Utero-placental tissues were obtained from the uterine horns ipsilateral and contralateral to the corpus luteum and separated into maternal caruncle (CAR); maternal endometrium, inter-caruncle (ICAR), and fetal membranes (FM). After collection, all tissues were snap frozen and stored at –80°C. There were no treatment × stage of gestation interactions (P &gt;0.13) on the mRNA expression of vascular endothelial growth factor (VEGF) or endothelial nitric oxide synthase (eNOS). Heifers on CON treatment had greater (P = 0.03) expression of VEGF compared with RES heifers in NP-ICAR. On d 50 expression of eNOS was increased (P = 0.05) compared with d 16 in P-CAR. Expression of eNOS mRNA was decreased (P = 0.04) on d 16 compared with d 34 and 50 in CON heifer. Gene expression of eNOS was increased (P &lt; 0.001) in the pregnant uterine horn compared with the NP uterine horn on d 34 and 50. Expression of eNOS was also increased (P &lt; 0.003) on d 34 and 50 in the pregnant uterine horn compared with FM. There was a maternal nutritional plane × stage of gestation interaction (P = 0.01) on the vascular ratio (vascular volume/tissue volume) in maternal tissues. The RES heifers had a greater vascular ratio on d 16 compared with d 34 and 50; whereas, CON heifers had a greater vascular ratio on d 34 compared with d 16 and 50. In the NP uterine horn, there was also an increase (P = 0.02) in vascular volume of FM from CON heifers compared with FM from RES heifers. We conclude that maternal nutrient restriction did alter both vascularity and mRNA expression of angiogenic factor in utero-placental tissues during the establishment of pregnancy in first parity beef heifers.

scholarly journals Hyperphosphorylation of fetal liver IGFBP-1 precedes slowing of fetal growth in nutrient-restricted baboons and may be a mechanism underlying IUGR

2020 ◽  
Vol 319 (3) ◽  
pp. E614-E628
Author(s):  
Jenica H. Kakadia ◽  
Bhawani B. Jain ◽  
Kyle Biggar ◽  
Austen Sutherland ◽  
Karen Nygard ◽  
...  
Keyword(s):  
Amino Acid ◽  
Fetal Liver ◽  
Control Diet ◽  
Nutrient Restriction ◽  
Mtor Inhibition ◽  
Group 13 ◽  
Umbilical Blood ◽  
Parallel Reaction Monitoring ◽  
Igf Binding ◽  
Igf Binding Protein

In cultured fetal liver cells, insulin-like growth factor (IGF) binding protein (IGFBP)-1 hyperphosphorylation in response to hypoxia and amino acid deprivation is mediated by inhibition of mechanistic target of rapamycin (mTOR) and activation of amino acid response (AAR) signaling and casein kinase (CK)2. We hypothesized that fetal liver mTOR inhibition, activation of AAR and CK2, and IGFBP-1 hyperphosphorylation occur before development of intrauterine growth restriction (IUGR). Pregnant baboons were fed a control (C) or a maternal nutrient restriction (MNR; 70% calories of control) diet starting at gestational day (GD) 30 (term GD 185). Umbilical blood and fetal liver tissue were obtained at GD 120 (C, n = 7; MNR, n = 10) and 165 (C, n = 7; MNR, n = 8). Fetal weights were unchanged at GD 120 but decreased at GD 165 in the MNR group (−13%, P = 0.03). IGFBP-1 phosphorylation, as determined by parallel reaction monitoring mass spectrometry (PRM-MS), immunohistochemistry, and/or Western blot, was enhanced in MNR fetal liver and umbilical plasma at GD 120 and 165. IGF-I receptor autophosphorylationTyr1135 (−64%, P = 0.05) was reduced in MNR fetal liver at GD 120. Furthermore, fetal liver CK2 (α/α′/β) expression, CK2β colocalization, proximity with IGFBP-1, and CK2 autophosphorylationTyr182 were greater at GD 120 and 165 in MNR vs. C. Additionally, mTOR complex (mTORC)1 (p-P70S6KThr389, −52%, P = 0.05) and mTORC2 (p-AktSer473, −56%, P < 0.001) activity were decreased and AAR was activated (p-GCN2Thr898, +117%, P = 0.02; p-eIF2αSer51, +294%, P = 0.002; p-ERKThr202, +111%, P = 0.03) in MNR liver at GD 120. Our data suggest that fetal liver IGFBP-1 hyperphosphorylation, mediated by mTOR inhibition and both AAR and CK2 activation, is a key link between restricted nutrient and oxygen availability and the development of IUGR.

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

2020 ◽  
Vol 98 (Supplement_4) ◽  
pp. 284-285
Author(s):  
Brandon I Smith ◽  
Manuel A Vasquez-Hidalgo ◽  
Kimberly A Vonnahme ◽  
Anna T Grazul-Bilska ◽  
Kendall C Swanson ◽  
...  
Keyword(s):  
Fetal Liver ◽  
Control Diet ◽  
National Research Council ◽  
Enrichment Analysis ◽  
Postnatal Growth ◽  
Pentose Phosphate ◽  
Nutrient Restriction ◽  
Pathway Enrichment Analysis ◽  
Phenylalanine Metabolism ◽  
Isoleucine Metabolism

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.

Basis of hematopoietic defects in platelet-derived growth factor (PDGF)-B and PDGF β-receptor null mice

Blood ◽  
2001 ◽  
Vol 97 (7) ◽  
pp. 1990-1998 ◽  
Author(s):  
Wolfgang E. Kaminski ◽  
Per Lindahl ◽  
Nancy L. Lin ◽  
Virginia C. Broudy ◽  
Jeffrey R. Crosby ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fetal Liver ◽  
Liver Cells ◽  
Platelet Derived Growth Factor ◽  
Wild Type ◽  
Liver Growth ◽  
Hematologic Disorders ◽  
Fetal Liver Cells ◽  
Β Receptor

Abstract Platelet-derived growth factor (PDGF)-B and PDGF β-receptor (PDGFRβ) deficiency in mice is embryonic lethal and results in cardiovascular, renal, placental, and hematologic disorders. The hematologic disorders are described, and a correlation with hepatic hypocellularity is demonstrated. To explore possible causes, the colony-forming activity of fetal liver cells in vitro was assessed, and hematopoietic chimeras were demonstrated by the transplantation of mutant fetal liver cells into lethally irradiated recipients. It was found that mutant colony formation is equivalent to that of wild-type controls. Hematopoietic chimeras reconstituted with PDGF-B−/−, PDGFRβ−/−, or wild-type fetal liver cells show complete engraftment (greater than 98%) with donor granulocytes, monocytes, B cells, and T cells and display none of the cardiovascular or hematologic abnormalities seen in mutants. In mouse embryos, PDGF-B is expressed by vascular endothelial cells and megakaryocytes. After birth, expression is seen in macrophages and neurons. This study demonstrates that hematopoietic PDGF-B or PDGFRβ expression is not required for hematopoiesis or integrity of the cardiovascular system. It is argued that metabolic stress arising from mutant defects in the placenta, heart, or blood vessels may lead to impaired liver growth and decreased production of blood cells. The chimera models in this study will serve as valuable tools to test the role of PDGF in inflammatory and immune responses.

scholarly journals Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

2013 ◽  
Vol 217 (3) ◽  
pp. 303-315 ◽  
Author(s):  
M B Mazzucco ◽  
R Higa ◽  
E Capobianco ◽  
M Kurtz ◽  
A Jawerbaum ◽  
...  
Keyword(s):  
Leptin Receptor ◽  
Fetal Liver ◽  
Liver Lipid ◽  
Saturated Fat ◽  
Receptor Expression ◽  
Lipid Concentration ◽  
Old Rats ◽  
Liver Lipid Concentration ◽  
Leptin Expression ◽  
Layer Chromatography

Metabolic alterations in obese and overweight mothers impact the placenta and the fetus, leading to anomalies in fetal growth and lipid accretion. The primary aim of the study was to examine the effect of a saturated fat-rich diet (FD) on growth, lipid accretion, and lipases, leptin and leptin receptor (ObR) expression in the placenta and fetal liver. We also aimed to find a role for fetal leptin in the modulation of placental and fetal liver lipase and ObR expression. Six-week-old rats were fed with a standard rat chow (control) or a 25% FD for 7 weeks until mating and during pregnancy. Also, in a group of control rats, fetuses were injected with leptin on days 19, 20, and 21 of pregnancy. On day 21, we assessed lipidemia, insulinemia, and leptinemia in mothers and fetuses. In the placenta and fetal liver, lipid concentration was assessed by thin layer chromatography (TLC) and the gene expression of lipoprotein lipase (LPL), endothelial lipase, insulin receptor (Insr), leptin, and ObR by RT-PCR. The FD induced hypertriglyceridemia and hyperleptinemia (P<0.01) in mothers and fetuses, an increase in maternal (P<0.05) and fetal weight (P<0.01), overaccumulation of lipids in fetal liver (P<0.01), and enhanced leptin expression in the placenta and fetal liver (P<0.05). Placental expression of IR and LPL was increased (P<0.05), and ObR decreased (P<0.05) in the FD group. Fetal administration of leptin induced the placental and fetal liver downregulation of ObR (P<0.05) and upregulation of LPL expression (P<0.05). The FD led to increased fetal lipid levels, which may result from high maternal lipid availability and fetal leptin effects.

scholarly journals Influence of intergenerational in utero parental energy and nutrient restriction on offspring growth in rural Gambia

2017 ◽  
Vol 31 (11) ◽  
pp. 4928-4934 ◽  
Author(s):  
Kamilla G. Eriksen ◽  
Elizabeth J. Radford ◽  
Matt J. Silver ◽  
Anthony J. C. Fulford ◽  
Rita Wegmüller ◽  
...  
Keyword(s):  
In Utero ◽  
Nutrient Restriction ◽  
Offspring Growth

Effects of dietary choline on liver lipid composition, liver histology and plasma biochemistry of juvenile yellowtail kingfish (Seriola lalandi)

2020 ◽  
pp. 1-15
Author(s):  
Angela Liu ◽  
Igor Pirozzi ◽  
Basseer M. Codabaccus ◽  
Frances Stephens ◽  
David S. Francis ◽  
...  
Keyword(s):  
Lipid Composition ◽  
De Novo ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Liver Lipid ◽  
Liver Histology ◽  
Plasma Biochemistry ◽  
Yellowtail Kingfish ◽  
Seriola Lalandi ◽  
Dietary Choline

Abstract Choline plays a crucial role in lipid metabolism for fish, and its deficiency in aquafeed has been linked to compromised health and growth performance. A 56-d experiment was conducted to examine the effects of dietary choline on lipid composition, histology and plasma biochemistry of yellowtail kingfish (Seriola lalandi; YTK; 156 g initial body weight). The dietary choline content ranged from 0·59 to 6·22 g/kg diet. 2-Amino-2-methyl-1-propanol (AMP) (3 g/kg) was added to diets, except for a control diet, to limit de novo choline synthesis. The results showed that the liver lipid content of YTK was similar among diets containing AMP and dominated by NEFA. In contrast, fish fed the control diet had significantly elevated liver TAG. Generally, the SFA, MUFA and PUFA content of liver lipid in fish fed diets containing AMP was not influenced by choline content. The SFA and MUFA content of liver lipid in fish fed the control diet was similar to other diets except for a decrease in PUFA. The linear relationship between lipid digestibility and plasma cholesterol was significant, otherwise most parameters were unaffected. When AMP is present, higher dietary choline reduced the severity of some hepatic lesions. The present study demonstrated that choline deficiency affects some plasma and liver histology parameters in juvenile YTK which might be useful fish health indicators. Importantly, the present study elucidated potential reasons for lower growth in choline-deficient YTK and increased the knowledge on choline metabolism in the fish.

scholarly journals Developmental regulation of cardiovascular function is dependent on both genotype and environment

2009 ◽  
Vol 297 (6) ◽  
pp. H2234-H2241 ◽  
Author(s):  
Brian S. Knight ◽  
Nana Sunn ◽  
Craig E. Pennell ◽  
S. Lee Adamson ◽  
Stephen J. Lye
Keyword(s):  
Cardiovascular Disease ◽  
Arterial Pressure ◽  
Complex Traits ◽  
Developmental Regulation ◽  
Control Diet ◽  
Cardiovascular Function ◽  
Mouse Strains ◽  
Nutrient Restriction ◽  
Genetic Dissection ◽  
Age Range

Adverse developmental environments can increase the risk of adult cardiovascular disease, but not all individuals are affected, suggesting the importance of genotype. Genetically distinct mouse strains allow the genetic dissection of complex traits; however, they have not been used to evaluate the developmental origins of adult cardiovascular disease. Our objective was to determine the effect of prenatal nutrient restriction (R) on adult cardiovascular function in A/J (AJ) and C57BL/6J (B6) mice and whether a postnatal high-fat (HF) diet exacerbates these effects. Pregnant AJ and B6 mice underwent a 30% R or ad libitum diet, and their offspring underwent a HF or control diet. Hypertension (+17 mmHg; P < 0.001) was observed in B6R mice at 9 wk, and their arterial pressure tended to remain high at 25 wk (+13 mmHg; not significant). In AJR mice, the normal decrement in arterial pressure over this age range in this strain was abolished. Heart rate prematurely increased in B6R and decreased in AJR (all; P < 0.05) mice from 9 to 25 wk. There was no effect of postnatal HF diet on these relationships. The Tei index (from a 26-wk microultrasound) was increased in both AJR and B6R mice (all; P < 0.05), suggesting an improved global myocardial performance. Neither R nor HF alone changed diastolic (ratio of E wave to A wave) or systolic (%fractional shortening) function in either strain; however, R and HE combined improved diastolic function in B6 ( P < 0.05) but not in AJ mice. Therefore, there are strain-dependent alterations in adult cardiovascular function in response to prenatal nutrient restriction. Unexpectedly, a postnatal HF diet did not exacerbate the effects of prenatal nutrient restriction on postnatal cardiovascular outcomes.

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