Maternal high fat intake affects the development and transcriptional profile of fetal intestine in late gestation using pig model
© Che et al. 2016
Received: 21 February 2016
Accepted: 3 May 2016
Published: 10 May 2016
The objective of this study was to investigate the effects of maternal high fat intake on intestinal development and transcriptional profile.
Eight gilts with similar age and body weight were randomly allocated into 2 groups receiving the control and high fat diets (HF diet) from d 30 to 90 of gestation, with 4 gilts each group and one gilt each pen. At d 90 of gestation, two fetuses each gilt were removed by cesarean section. Intestinal samples were collected for analysis of morphology, enzyme activities and transcriptional profile.
The results showed that feeding HF diet markedly increased the fetal weight and lactase activity, also tended to increase intestinal morphology. Porcine Oligo Microarray analysis indicated that feeding HF diet inhibited 64 % of genes (39 genes down-regulated while 22 genes up-regulated),which were related to immune response, cancer and metabolism, also markedly modified 33 signal pathways such as antigen processing and presentation, intestinal immune network for IgA production, Jak-STAT and TGF-ß signaling transductions, pathways in colorectal cancer and glycerolipid metabolism.
Collectively, it could be concluded that maternal high fat intake was able to increase fetal weight and lactase activity, however, it altered the intestinal immune response, signal transduction and metabolism.
Gastrointestinal tract (GIT), as an internal organ to digest nutrients and resist exogenous antigens, starts to develop at early gestation and mature rapidly in late gestation for extra-uterine life . The functional maturation of GIT occurs in both pre- and postnatal period, which is largely influenced by maternal nutrition . Maternal diet has been shown to affect the fetal development and organ function in mammalian animals . Our recent study also suggests that maternal nutrition levels could affect the intestinal development and function, in which maternal over-nutrition would improve intestinal morphology, enzyme activities and gene expressions of nutrient transporters in newborn pigs . However, it has been reported that maternal high-fat intake or –related obesity could impair gut barrier, enhance gene expression of pro-inflammatory cytokines in offspring intestine, thus predisposes offspring to inflammatory bowel disease [5, 6]. However, the underlying mechanism for the effects of maternal high fat intake on the intestinal development and function are limited. The current study was designed to investigate the effects of maternal high fat intake on fetal intestinal development and function by measuring parameters on morphology, enzyme activities and transcriptional profiles. Oligo Microarray was used to analyze the genomic response of fetal intestine to maternal high fat intake. Pigs were chosen as the experimental animal, because it is generally accepted to be closer to humans than other laboratory or domestic animals in terms of gastrointestinal anatomy, physiology, nutrition and microbiota [2, 7–9].
The experimental procedure was approved by the University of Sichuan Agricultural Animal Care Advisory committee, and followed the current law of animal protection.
Animals and diets
A total of 8 Meishan (MS) gilts (aged at 266 ± 15 d, initial body weight at 73 ± 4 kg) were used in this study. After inseminated with MS semen, eight gilts were randomly allocated to receive control diet (CON diet with 14 % Protein, 34.7 % Starch and 2.8 % Fat) and high fat diet (HF diet with 14 % Protein, 34.7 % Starch and 7.3 % Fat), respectively. The 4.5 % of soy oil was added into CON diet to formulate HF diet, as a result, HF diet contained digestive energy (DE) at 3.0 Mcal/kg, while CON diet contained DE at 2.6 Mcal/kg. According to the fatty acids contents of feed ingredients by NRC (2012), the contents of saturated, mono- and polyunsaturated fatty acids were 0.25 %, 0.48 %, 0.83 % in CON diet and 0.84 %, 1.78 %, 3.44 % in HF diet, respectively. The other nutrient levels were similar between 2 diets, meeting or exceeding nutrient requirements recommended by NRC (2012). All gilts were housed individually in stall (2.5 m length × 1.6 m width), receiving the same amount of diets at 2.0 kg from d 1 to 30 of gestation and 2.5 kg from d 30 to 90 of gestation, with free access to water. Environmental temperature was maintained at approximately 24 °C during the experiment.
At d 90 of gestation, gilts were weighed (in average 128 kg at HF vs. 117 kg at CON group) and anaesthetized by intramuscularly injecting Zoletil 50 at the dose of 0.1 mg/kg (Virbac, France), then the uterus were removed from gilts. Two fetuses near the average fetal weight were collected each gilt. As the previous study, duodenal, jejunal and ileal samples (approximately 2 cm) were preserved in 4 % paraformaldehyde solution, then embedded in paraffin. Each tissue sample of duodenum, jejunum and ileum was used to prepare 5 slides, each slide had three sections (5 mm thickness), which were stained with eosin and haematoxylin, 20 well-oriented villi and crypts each section were measured for morphology (Optimus software version 6.5, Media Cybergenetics, North Reading, MA, USA), and villous height to crypt depth ratio (VCR) was calculated . A section of duodenum, jejunum and ileum tissues were collected and snap-frozen in liquid nitrogen, then stored at −80 °C for analysis of enzyme activities, RNA microarray and gene expression.
According to the previous study, the thawing samples of jejunum and ileum were weighed (approximately 2 g), then 9 times volume of 50 mM Tris–HCl buffer (pH 7 · 0) than the sample weight were added and homogenized for 40 s by homogenate machine (Homogenizer Power Gen 125™, ThermoFisher Scientific, MA, USA) and centrifuged at 3000 g for 10 min, the supernatant was collected and stored at −20 °C . Total protein was extracted from the supernatant and protein concentration was determined by bicinchoninic acid protein assay with bovine serum albumin as the standard (Solarbio, Inc., Beijing, China). Activities of disaccharidase including maltase, sucrase and lactase were measured using commercial kits (Nanjing Jiancheng Bioengineering, Nanjing, China). The absorbance at 450 nm was determined with spectrophotometer (Beckman Coulter DU-800; Beckman Coulter, Inc., CA, USA). Activities of disaccharidase were presented as U/mg protein. One unit (U) was defined by 1 nmol of maltose, sucrose and lactose as a substrate for the enzymatic reaction, respectively.
The frozen ileum tissues were used for RNA extraction, 4 sections around luminal circle each tissue were collected and pooled for RNA extraction. Total RNA was extracted using Trizol reagent (Invitrogen, Carlsbad, CA, USA) and quantified using spectrophotometry based on absorbance at 260 nm, the RNA quality was monitored using Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA). The equal amount of RNA from 2 fetus each gilt were pooled together.
Porcine oligo microarray
As in our previous study, Agilent Porcine Oligo Microarray (4 × 44 K) containing more than 40,000 probes were used . Cyanine-3 (Cy3)-labeled cRNA was prepared from 0.5 μg RNA using the One-Color Low RNA Input Linear Amplification PLUS kit (Agilent Technologies,Palo Alto, CA, USA) according to the manufacturer’s instructions, and followed by the RNeasy column purification (Qiagen, Valencia, CA, USA). Dye incorporation and cRNA yield were checked with the NanoDrop ND-1000 Spectrophotometer. Microarrays were hybridized at 65 °C for 17 h and washed with a Gene Expression Washing Buffer Kit (Agilent Technologies, Palo Alto, CA, USA). Slides were scanned with an Agilent microarray scanner.
Microarray data collection and analysis
Microarray data were collected and analyzed using Agilent G2567AA Feature Extraction software, following Agilent’s direct labeling protocol. The quantile method was used to normalize the probe intensities across the whole set of arrays. Three criteria were used to determine statistically significant differential expression of intestinal genes between fetus from CON and HF gilts: 1) statistical significance: P value as determined by t-test < 0.05; 2) reliability: a spot quality flag P (“P,” a quality flag assigned by the software package); 3) relevance: a minimal fold change between the means of the 2 groups >1.5.
Primer sequences of genes selected for analysis by real-time RT-PCR
Primer sequence (5′ ~ 3′)
Product length (bp)
The detected data by samples from two fetuses each gilt were averaged and taken as one independent data involving into statistical analysis model. In addition to Oligo Microarray and qPCR data, all other data on growth performance, intestinal morphology and enzyme activities were analyzed via the t Student’s t test for a completely randomized design using SAS (SAS, Cary, NC). Results were expressed as the mean ± SD. Differences were considered to be significant when P <0.05, while a tendency was considered when 0.05 < P < 0.10.
Feeding HF diet markedly increased the fetal weight (in average 585 g vs.508 g, P < 0.05) at d 90 of gestation.
Morphology and enzyme activities
Differentially expressed genes in fetal intestine
Maternal high fat intake markedly regulated intestinal gene expressions related to immune response, signal transduction, cancer and metabolism
chemokine (C-C motif) receptor 7
heat shock 70 kDa protein 1-like
CD8a molecule (CD8A)
CD3e molecule, epsilon (CD3-TCR complex) (CD3E)
serine/threonine kinase 17b
CD40 molecule, TNF receptor superfamily member 5
MHC class II histocompatibility antigen SLA-DQA
proline-serine-threonine phosphatase interacting protein 1
SLAM family member 6
tumor protein p53 inducible nuclear protein 1
family with sequence similarity 78, member A
BCL2-related protein A1
Rho GTPase activating protein 25
signal transducer and activator of transcription 2
Rho GTPase activating protein 30
BCL2-related protein A1
interleukin 10 receptor, beta
mRNA, clone:MLN010057G03, expressed in mesenteric lymph nodes
lymphocyte cytosolic protein 1 (L-plastin)
negative regulator of reactive oxygen species
bone morphogenetic protein 7
phosphoinositide-3-kinase, regulatory subunit 5
regulator of G-protein signaling 14
MHC class II histocompatibility antigen SLA-DRB1
lysophosphatidic acid receptor 2
Thy-1 cell surface antigen
transforming growth factor, beta 1
bromodomain adjacent to zinc finger domain, 1A
coiled-coil domain containing 69
leucine-rich repeat kinase 2
MHC class I antigen 1
CD74 molecule, major histocompatibility complex, class II invariant chain
superoxide dismutase 2, mitochondrial
interleukin enhancer binding factor 2
cytochrome P450, family 39, subfamily A, polypeptide 1
ataxia, cerebellar, Cayman type
mRNA, clone:OVR010041A03, expressed in ovary
mRNA, clone:UTR010010H08, expressed in uterus.
SPARC-like 1 (hevin)
mRNA, clone:OVR010041A03, expressed in ovary
connective tissue growth factor
mRNA, clone: HTMT10103A12, expressed in hypothalamus
inhibitor of DNA binding 4, dominant negative helix-loop-helix protein
secreted protein, acidic, cysteine-rich (osteonectin)
meprin A, alpha (PABA peptide hydrolase)
ADP-ribosylation factor-like 10
actin, alpha 2, smooth muscle, aorta
shisa family member 2
ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)
oculocerebrorenal syndrome of Lowe
sulfotransferase family 1E, estrogen-preferring, member 1
Differentially expressed genes in fetal intestine by maternal high fat intake and validated by qPCR
Analysis of gene ontology and signal pathway
The markedly modified signal pathways in fetal intestine of gilts fed HF diet
Antigen processing and presentation
Autoimmune thyroid disease
Cell adhesion molecules
Cytokine-cytokine receptor interaction
Hematopoietic cell lineage
Intestinal immune network for IgA production
Neuroactive ligand-receptor interaction
Type I diabetes mellitus
Jak-STAT signaling pathway
Pathways in cancer
Systemic lupus erythematosus
Adipocytokine signaling pathway
Chemokine signaling pathway
Fc gamma R-mediated phagocytosis
T cell receptor signaling pathway
Leukocyte transendothelial migration
Acute myeloid leukemia
Arrhythmogenic right ventricular cardiomyopathy
TGF-beta signaling pathway
Aldosterone-regulated sodium reabsorption
Type II diabetes mellitus
In this study, maternal high fat intake increased intestinal villous height and lactase activity, which is similar as our recent study that maternal over-nutrition markedly increased birth weight, accordingly intestinal morphology as well as lactase activity . It may be rational that the heavier birth weight needs higher lactase activity in preparation for better degradation of lactose, which is a crucial energy source in neonatal period . However, a recent study indicated that maternal high fat intake would induce intestinal inflammation and poor gut barrier function in the offspring of mice . In this study, porcine oligo miacro array analysis was used to determine the genomic response of intestine to maternal high fat intake, in an attempt to reveal the potential mechanism. According to the strict selection criteria, we found a total of 61 genes were differentially regulated and 64 % of them (39 genes) was down-regulated by HF diet. With the bioinformatics analysis, these down-regulated genes were mainly involved in process of immune response, signaling transduction, pathways in cancer and metabolism, suggesting the inhibitory effects of maternal high fat intake on certain biological events. The maternal diet fat composition could change the maternal-to-fetal fatty acid transfer and intestinal membrane n-6 and n-3 fatty acids composition of newborns, thus altering intestinal function . In this study, therefore, it is rational that the addition of soy oil in maternal diet would induce alterations in intestinal physiology of fetus. Obviously, antigen processing and presentation in intestine could be inhibited by feeding HF diet, as indicated by the markedly decreasing gene expressions (i.e. SLA-1, SLA -DRB1, SLA-DQA1, CD74 and CD8, 1.5 ~ 2.5 fold reduction). Particularly, SLA-1, SLA -DRB1 and SLA-DQA1 are belonged to the highly polymorphic swine leucocyte antigen genes, which determine the immune response to disease and vaccine . Among them, SLA-1 could interact with natural killer cells to prevent cytotoxicity , while SLA-DRB1 and -DQA1 mainly present exogenous peptides for T cells [18, 19]. Previous studies have shown that maternal high fat intake impaired intestinal barrier and immune system through altering immune cell homeostasis, such as the number of T cells and macrophages . Furthermore, intestinal immune network for IgA production may be impaired by HF diet, as shown by the decreasing gene expression of CD40, IL-6 and TGF-ß. These genes are required for B cells proliferation and differentiation in Peyer’s patches, their down-regulation would reduce the homing of T cells and IgA+ plasma cells to the intestine, thus impair the immune homeostasis of intestine [20, 21].
Several signal transduction pathways related to inflammatory and immune response were affected by maternal high fat intake. For example, the TGF-β signaling pathway was affected by HF diet, as indicated by the decreasing gene expression of TGF-β and Bmp7 (approximately 1.6 fold reduction). TGF-β is a multifunctional factor regulating cell growth, adhesion and differentiation [22, 23], also exerting anti-inflammatory effects by inhibiting NF-κB expression in the intestinal epithelium . The oral administration of TGF-β has been shown to decrease severity and incidence of necrotizing enterocolitis in neonatal rat necrotizing enterocolitis model . In addition, feeding HF diet affected intestinal Jak-STAT signaling pathway, as shown by the decreasing gene expression of IL6, STAT2 and PIK3R5. The Jak-STAT signaling pathway is required for T cell differentiation, B cell maturation and secretion of sIgA , these down-regulated genes by HF diet may induce the abnormal intestinal innate immune response. Similarly, previous study demonstrated that maternal high protein diet would decrease liver mass, associated with altering gene expressions mapping to Jak-STAT signaling pathway in mouse offspring .
Furthermore, the lower expressions of TGF-β and PIK3R5 genes by HF diet may affect the progression of colorectal cancer. TGF-β1/Smads signaling pathway was demonstrated to mediate epithelial-to-mesenchymal transition, associated with the progression of colorectal cancer . Mutation of PIK3R5 and other genes (i.e. PRKCZ, PTEN, RHEB and RPS6KB1) have altered PI3K signaling pathway, which is the central pathway for both colorectal and breast cancers . Recent studies also indicated that maternal high fat diet would modify the susceptibility to breast cancer [29, 30], meanwhile it is dependent on fat or oil sources [31–33].
In this study, moreover, the markedly reduced glycerol kinase by feeding HF diet suggests the intestinal metabolism was altered. Glycerol kinase is required to release glycerol from glycerol-3-phosphate and dihydroxyacetone, and intestinal glycerol could produce 20 ~ 25 % of total endogenous glucose under insulinopenia, suggesting the important role of glycerol in intestinal metabolism . Although most of genes were markedly down-regulated by HF diet, some of genes (SOD2, CYP39A1, CCN2, SPARC et al.) were up-regulated. Particularly, SOD2, as an anti-oxidative enzyme in living cells, was highly expressed (1.75 fold change, P = 0.04). Likewise, a recent study demonstrated that maternal high energy intake increased the expression of SOD in offspring ileum . Previous study indicated that the increasing SOD gene is not necessarily associated with a better antioxidant capability, for example, the inflamed intestinal mucosa has been shown to contain higher SOD protein compared with normal tissues . In addition, we found that feeding HF diet markedly increased gene expression of SULT1E by both DNA Microarray and RT-PCR analysis. SULT1E, as an estrogen-preferring drug metabolizing enzyme, its highly expression may be an compensatory response to high circulating estrogen, which occurs in dams fed high fat diet . It has been shown that the estrogen deletion by SULT1E over-expression is associated with the risk of developing different types of cancers [28, 37].
In summary, maternal high fat intake was able to increase fetal and intestinal weights as well as lactase activity, however, it altered the intestinal immune response, signal transduction and metabolism.
We would like to thank the staff at our laboratory for their ongoing assistance.
The present study was supported by the National Natural Science Foundation of China (31101727) and the National Basic Research Program (973 Program) of China (No. 2013CB127306).
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Wu G, Bazer FW, Wallace JM, Spencer TE. Board-invited review: intrauterine growth retardation: implications for the animal sciences. J Anim Sci. 2006;84:2316–37.View ArticlePubMedGoogle Scholar
- Sangild PT. Gut responses to enteral nutrition in preterm infants and animals. Exp Biol Med (Maywood). 2006;231:1695–711.Google Scholar
- Pinheiro DF, Pinheiro PF, Buratini Jr J, Castilho AC, Lima PF, Trinca LA, Vicentini-Paulino Mde L. Maternal protein restriction during pregnancy affects gene expression and immunolocalization of intestinal nutrient transporters in rats. Clin Sci (Lond). 2013;125:281–9.View ArticleGoogle Scholar
- Cao M, Che L, Wang J, Yang M, Su G, Fang Z, Lin Y, Xu S, Wu D. Effects of maternal over- and undernutrition on intestinal morphology, enzyme activity, and gene expression of nutrient transporters in newborn and weaned pigs. Nutrition. 2014;30:1442–7.View ArticlePubMedGoogle Scholar
- Xue Y, Wang H, Du M, Zhu MJ. Maternal obesity induces gut inflammation and impairs gut epithelial barrier function in nonobese diabetic mice. J Nutr Biochem. 2014;25:758–64.View ArticlePubMedPubMed CentralGoogle Scholar
- Yan X, Huang Y, Wang H, Du M, Hess BW, Ford SP, Nathanielsz PW, Zhu MJ. Maternal obesity induces sustained inflammation in both fetal and offspring large intestine of sheep. Inflamm Bowel Dis. 2011;17:1513–22.View ArticlePubMedPubMed CentralGoogle Scholar
- Gonzalez-Bulnes A, Astiz S, Ovilo C, Lopez-Bote CJ, Sanchez-Sanchez R, Perez-Solana ML, Torres-Rovira L, Ayuso M, Gonzalez J. Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance. J Endocrinol. 2014;223:M17–29.View ArticlePubMedGoogle Scholar
- Zhang Q, Widmer G, Tzipori S. A pig model of the human gastrointestinal tract. Gut Microbes. 2013;4:193–200.View ArticlePubMedPubMed CentralGoogle Scholar
- Heinritz SN, Mosenthin R, Weiss E. Use of pigs as a potential model for research into dietary modulation of the human gut microbiota. Nutr Res Rev. 2013;26:191–209.View ArticlePubMedGoogle Scholar
- Han F, Hu L, Xuan Y, Ding X, Luo Y, Bai S, He S, Zhang K, Che L. Effects of high nutrient intake on the growth performance, intestinal morphology and immune function of neonatal intra-uterine growth-retarded pigs. Br J Nutr. 2013;110:1819–27.View ArticlePubMedGoogle Scholar
- Hu L, Liu Y, Yan C, Peng X, Xu Q, Xuan Y, Han F, Tian G, Fang Z, Lin Y, et al. Postnatal nutritional restriction affects growth and immune function of piglets with intra-uterine growth restriction. Br J Nutr. 2015;114:53–62.View ArticlePubMedGoogle Scholar
- Che L, Chen H, Yu B, He J, Zheng P, Mao X, Yu J, Huang Z, Chen D. Long-term intake of pea fiber affects colonic barrier function, bacterial and transcriptional profile in pig model. Nutr Cancer. 2014;66:388–99.View ArticlePubMedGoogle Scholar
- Innis SM, Dai C, Wu X, Buchan AM, Jacobson K. Perinatal lipid nutrition alters early intestinal development and programs the response to experimental colitis in young adult rats. Am J Physiol Gastrointest Liver Physiol. 2010;299:G1376–1385.View ArticlePubMedGoogle Scholar
- Boudry G, Douard V, Mourot J, Lalles JP, Le Huerou-Luron I. Linseed oil in the maternal diet during gestation and lactation modifies fatty acid composition, mucosal architecture, and mast cell regulation of the ileal barrier in piglets. J Nutr. 2009;139:1110–7.View ArticlePubMedGoogle Scholar
- Desaldeleer C, Ferret-Bernard S, de Quelen F, Le Normand L, Perrier C, Savary G, Rome V, Michel C, Mourot J, Le Huerou-Luron I, Boudry G. Maternal 18:3n-3 favors piglet intestinal passage of LPS and promotes intestinal anti-inflammatory response to this bacterial ligand. J Nutr Biochem. 2014;25:1090–8.View ArticlePubMedGoogle Scholar
- Heyman MB, Committee on N. Lactose intolerance in infants, children, and adolescents. Pediatrics. 2006;118:1279–86.View ArticlePubMedGoogle Scholar
- Ho CS, Lunney JK, Lee JH, Franzo-Romain MH, Martens GW, Rowland RR, Smith DM. Molecular characterization of swine leucocyte antigen class II genes in outbred pig populations. Anim Genet. 2010;41:428–32.PubMedGoogle Scholar
- Lunney JK, Ho CS, Wysocki M, Smith DM. Molecular genetics of the swine major histocompatibility complex, the SLA complex. Dev Comp Immunol. 2009;33:362–74.View ArticlePubMedGoogle Scholar
- Summerfield A, Guzylack-Piriou L, Schaub A, Carrasco CP, Tache V, Charley B, McCullough KC. Porcine peripheral blood dendritic cells and natural interferon-producing cells. Immunology. 2003;110:440–9.View ArticlePubMedPubMed CentralGoogle Scholar
- Wang D, Dubois RN, Richmond A. The role of chemokines in intestinal inflammation and cancer. Curr Opin Pharmacol. 2009;9:688–96.View ArticlePubMedPubMed CentralGoogle Scholar
- Chu VT, Beller A, Rausch S, Strandmark J, Zanker M, Arbach O, Kruglov A, Berek C. Eosinophils promote generation and maintenance of immunoglobulin-A-expressing plasma cells and contribute to gut immune homeostasis. Immunity. 2014;40:582–93.View ArticlePubMedGoogle Scholar
- Massagué J. TGFβ in cancer. Cell. 2008;134:215–30.View ArticlePubMedPubMed CentralGoogle Scholar
- Van’t Land B, Meijer H, Frerichs J, Koetsier M, Jager D, Smeets R, M'Rabet L, Hoijer M. Transforming Growth Factor-β2 protects the small intestine during methotrexate treatment in rats possibly by reducing stem cell cycling. Br J Cancer. 2002;87:113–8.Google Scholar
- Shiou SR, Yu Y, Guo Y, Westerhoff M, Lu L, Petrof EO, Sun J, Claud EC. Oral administration of transforming growth factor-beta1 (TGF-beta1) protects the immature gut from injury via Smad protein-dependent suppression of epithelial nuclear factor kappaB (NF-kappaB) signaling and proinflammatory cytokine production. J Biol Chem. 2013;288:34757–66.View ArticlePubMedPubMed CentralGoogle Scholar
- Heneghan AF, Pierre JF, Kudsk KA. JAK-STAT and intestinal mucosal immunology. JAKSTAT. 2013;2:e25530.PubMedPubMed CentralGoogle Scholar
- Vanselow J, Kucia M, Langhammer M, Koczan D, Rehfeldt C, Metges CC. Hepatic expression of the GH/JAK/STAT/IGF pathway, acute-phase response signalling and complement system are affected in mouse offspring by prenatal and early postnatal exposure to maternal high-protein diet. Eur J Nutr. 2011;50:611–23.View ArticlePubMedGoogle Scholar
- Ji Q, Liu X, Han Z, Zhou L, Sui H, Yan L, Jiang H, Ren J, Cai J, Li Q. Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression. BMC Cancer. 2015;15:1.View ArticleGoogle Scholar
- Wood LD, Parsons DW, Jones S, Lin J, Sjöblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318:1108–13.View ArticlePubMedGoogle Scholar
- Montales MT, Melnyk SB, Simmen FA, Simmen RC. Maternal metabolic perturbations elicited by high-fat diet promote Wnt-1-induced mammary tumor risk in adult female offspring via long-term effects on mammary and systemic phenotypes. Carcinogenesis. 2014;35:2102–12.View ArticlePubMedPubMed CentralGoogle Scholar
- de Oliveira AF, Fontelles CC, Rosim MP, de Oliveira TF, de Melo Loureiro AP, Mancini-Filho J, Rogero MM, Moreno FS, de Assis S, Barbisan LF, et al. Exposure to lard-based high-fat diet during fetal and lactation periods modifies breast cancer susceptibility in adulthood in rats. J Nutr Biochem. 2014;25:613–22.View ArticlePubMedPubMed CentralGoogle Scholar
- Mabasa L, Cho K, Walters MW, Bae S, Park CS. Maternal dietary canola oil suppresses growth of mammary carcinogenesis in female rat offspring. Nutr Cancer. 2013;65:695–701.View ArticlePubMedGoogle Scholar
- Czuba AK, Mazurkiewicz M, Stanimirova-Daszykowska I. Enrichment of maternal diet with conjugated linoleic acids influences desaturases activity and fatty acids profile in livers and hepatic microsomes of the offspring with 7, 12-dimethylbenz [a] anthracene-induced mammary tumors. Acta Pol Pharm. 2014;71:747.PubMedGoogle Scholar
- Su H-M, Hsieh P-H, Chen H-F. A maternal high n-6 fat diet with fish oil supplementation during pregnancy and lactation in rats decreases breast cancer risk in the female offspring. J Nutr Biochem. 2010;21:1033–7.View ArticlePubMedGoogle Scholar
- Croset M, Rajas F, Zitoun C, Hurot J-M, Montano S, Mithieux G. Rat small intestine is an insulin-sensitive gluconeogenic organ. Diabetes. 2001;50:740–6.View ArticlePubMedGoogle Scholar
- Kruidenier L, Kuiper I, van Duijn W, Marklund SL, van Hogezand RA, Lamers CB, Verspaget HW. Differential mucosal expression of three superoxide dismutase isoforms in inflammatory bowel disease. J Pathol. 2003;201:7–16.View ArticlePubMedGoogle Scholar
- Hilakivi-Clarke L, Clarke R, Onojafe I, Raygada M, Cho E, Lippman M. A maternal diet high in n − 6 polyunsaturated fats alters mammary gland development, puberty onset, and breast cancer risk among female rat offspring. Proc Natl Acad Sci. 1997;94:9372–7.View ArticlePubMedPubMed CentralGoogle Scholar
- Sharda DR, Miller-Lee JL, Kanski GM, Hunter JC, Lang CH, Kennett MJ, Korzick DH. Comparison of the agar block and Lieber–DeCarli diets to study chronic alcohol consumption in an aging model of Fischer 344 female rats. J Pharmacol Toxicol Methods. 2012;66:257–63.View ArticlePubMedPubMed CentralGoogle Scholar