scholarly journals Impact of Maternal Malnutrition on Gut Barrier Defense: Implications for Pregnancy Health and Fetal Development

Nutrients ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 1375 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high fat diet (HF). At day 18.5 (term = 19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

scholarly journals Impact of maternal malnutrition on gut barrier defence: implications for pregnancy health and fetal development.

2019 ◽  
Author(s):  
Sebastian A. Srugo ◽  
Enrrico Bloise ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Control Diet ◽  
Paneth Cell ◽  
Goblet Cells ◽  
Maternal Malnutrition ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Enteric Glial Cells ◽  
Host Microbe Interactions ◽  
And Function

Small intestinal Paneth cells, enteric glial cells (EGC), and goblet cells maintain gut mucosal integrity, homeostasis, and influence host physiology locally and through the gut-brain axis. Little is known about their roles during pregnancy, or how maternal malnutrition impacts these cells and their development. Pregnant mice were fed a control diet (CON), undernourished by 30% vs. control (UN), or fed a high-fat diet (HF). At day 18.5 (term=19), gut integrity and function were assessed by immunohistochemistry and qPCR. UN mothers displayed reduced mRNA expression of Paneth cell antimicrobial peptides (AMP; Lyz2, Reg3g) and an accumulation of villi goblet cells, while HF had reduced Reg3g and mucin (Muc2) mRNA and increased lysozyme protein. UN fetuses had increased mRNA expression of gut transcription factor Sox9, associated with reduced expression of maturation markers (Cdx2, Muc2), and increased expression of tight junctions (TJ; Cldn-7). HF fetuses had increased mRNA expression of EGC markers (S100b, Bfabp, Plp1), AMP (Lyz1, Defa1, Reg3g), and TJ (Cldn-3, Cldn-7), and reduced expression of an AMP-activator (Tlr4). Maternal malnutrition altered expression of genes that maintain maternal gut homeostasis, and altered fetal gut permeability, function, and development. This may have long-term implications for host-microbe interactions, immunity, and offspring gut-brain axis function.

scholarly journals Perinatal caprine milk oligosaccharides consumption alters maternal and offspring liver gene expression

2020 ◽  
Author(s):  
Caroline Thum ◽  
Wayne Young ◽  
Nicole C Roy ◽  
Warren C McNabb
Keyword(s):  
Gene Expression ◽  
Lipid Metabolism ◽  
Energy Balance ◽  
Visceral Fat ◽  
Control Diet ◽  
Milk Oligosaccharides ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Caprine Milk ◽  
Liver Gene

Abstract Consumption of caprine milk oligosaccharides (CMO) by dams during gestation and lactation, compared to a control diet or a diet supplemented with galacto-oligosaccharides (GOS), was associated with decreased maternal liver weight, increased offspring body weight and length at weaning, and increased offspring visceral fat and serum leptin concentration 30 days after weaning. These changes suggest that dietary CMO alters lipid metabolism, both in dams and offspring. We hypothesized that perinatal CMO intake affected expression of maternal genes in the liver involved in energy metabolism, and programmed pups’ metabolic function leading to increased post-weaning visceral adiposity. To characterise the effects of perinatal consumption of CMOs on maternal and offspring liver gene expression, C57BL/6 mice were fed either a control, CMO, or GOS diet from mating to weaning. From weaning, half of the pups from each maternal group were fed the control diet for 30 days. Microarray analysis was conducted on liver samples from dams and offspring. Differences in the expression of genes involved in lipid metabolism were observed in dams and changes in expression of hepatic genes involved in energy balance and steroid metabolism were observed in pups at weaning. Increased visceral fat was observed in pups 30 days. Perinatal consumption of CMO diet affected infant lipid metabolism, which may be related to altered expression of genes in the liver involved in energy balance and lipid metabolism in dams.

scholarly journals Sex-Dimorphic Behavioral Alterations and Altered Neurogenesis in U12 Intron Splicing-Defective Zrsr1 Mutant Mice

2019 ◽  
Vol 20 (14) ◽  
pp. 3543 ◽  
Author(s):  
Francisco Alén ◽  
Isabel Gómez-Redondo ◽  
Patricia Rivera ◽  
Juan Suárez ◽  
Priscila Ramos-Ibeas ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Intron Retention ◽  
Mutant Mice ◽  
Behavioral Alterations ◽  
Altered Expression ◽  
Cell Network ◽  
Expression Of Genes ◽  
Adult Cell ◽  
Controlling Behavior ◽  
And Function

Mutant mice with respect to the splicing factor Zrsr1 present altered spermatogenesis and infertility. To investigate whether Zrsr1 is involved in the homeostatic control that the hypothalamus exerts over reproductive functions, we first analyzed both differential gene and isoform expression and alternative splicing alterations in Zrsr1 mutant (Zrsr1mu) hypothalamus; second, we analyzed the spontaneous and social behavior of Zrsr1mu mice; and third, we analyzed adult cell proliferation and survival in the Zrsr1mu hypothalamus. The Zrsr1mu hypothalamus showed altered expression of genes and isoforms related to the glutathione metabolic process, synaptonemal complex assembly, mRNA transport, and altered splicing events involving the enrichment of U12-type intron retention (IR). Furthermore, increased IR in U12-containing genes related with the prolactin, progesterone, and gonadotropin-releasing hormone (GnRH) reproductive signaling pathway was observed. This was associated with a hyperactive phenotype in both males and females, with an anxious phenotype in females, and with increased social interaction in males, instead of the classical aggressive behavior. In addition, Zrsr1mu females but not males exhibited reduced cell proliferation in both the hypothalamus and the subventricular zone. Overall, these results suggest that Zrsr1 expression and function are relevant to organization of the hypothalamic cell network controlling behavior.

scholarly journals Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life

2015 ◽  
Vol 113 (3) ◽  
pp. 403-413 ◽  
Author(s):  
Filipa Rocha ◽  
Jorge Dias ◽  
Sofia Engrola ◽  
Paulo Gavaia ◽  
Inge Geurden ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Control Diet ◽  
Saline Group ◽  
Long Term Effects ◽  
Altered Expression ◽  
Expression Levels ◽  
High Carbohydrate ◽  
Expression Of Genes ◽  
Specific Regulation

Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 m) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP–6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [14C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [14C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

scholarly journals Maternal malnutrition impacts placental morphology and transport. An origin for poor offspring growth and vulnerability to disease

2019 ◽  
Author(s):  
Kristin L Connor ◽  
Mark Kibschull ◽  
Elzbieta Matysiak-Zablocki ◽  
Tina Tu-Thu Ngoc Nguyen ◽  
Stephen G Matthews ◽  
...  
Keyword(s):  
Mrna Expression ◽  
High Fat Diet ◽  
Control Diet ◽  
Transport Systems ◽  
Fetal Blood ◽  
Maternal Malnutrition ◽  
Fatty Acid Binding ◽  
Protein Levels ◽  
Offspring Growth ◽  
Lipid Transporter

AbstractThe placenta promotes fetal growth through nutrient transfer and selective barrier systems. An optimally developed placenta can adapt to changes in the pregnancy environment, buffering the fetus from adverse exposures. We hypothesised that the placenta adapts differently to suboptimal maternal diets, evidenced by changes in placental morphology, developmental markers, and key transport systems. Mice were fed a control diet (CON) during pregnancy, or undernourished (UN) by 30% of control intake from gestational day (GD)5.5-18.5, or fed 60% high fat diet (HF) eight weeks before and during pregnancy. At GD18.5, placental morphometry, development, and transport were assessed. Junctional and labyrinthine areas of UN and HF placentae were smaller than CON by >10%. Fetal blood space area and fetal blood space:fetal weight ratios were reduced in HF vs. CON and UN. Trophoblast giant cell marker Ctsq mRNA expression was lower in UN vs. HF, and expression of glycogen cell markers Cx31.1 and Pcdh12 was lower in HF vs. UN. Efflux transporter Abcb1a mRNA expression was lower in HF vs. UN, and Abcg2 expression was lower in UN vs. HF. mRNA expression of fatty acid binding protein Fabppm was higher in UN vs. CON and HF. mRNA and protein levels of the lipid transporter FAT/CD36 were lower in UN, and FATP4 protein levels were lower in HF vs. UN. UN placentae appear less mature with aberrant transport. HF placentae adapt to excessive nutrient supply. Understanding placental adaptations to common nutritional adversities may reveal mechanisms underlying the developmental origins of later disease.

scholarly journals Altered expression of a unique set of genes reveals complex etiology of Schizophrenia

2017 ◽  
Author(s):  
Ashutosh Kumar ◽  
Himanshu Narayan Singh ◽  
Vikas Pareek ◽  
Khursheed Raza ◽  
Pavan Kumar ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Mrna Expression ◽  
Brain Regions ◽  
Contributing Factors ◽  
Altered Expression ◽  
Expression Of Genes ◽  
Affy Package ◽  
Post Mortem Brain ◽  
A Genome ◽  
Neuronal Functions

AbstractPurposeThe etiology of schizophrenia is extensively debated, and multiple factors have been contended to be involved. A panoramic view of the contributing factors in a genome-wide study can be an effective strategy to provide a comprehensive understanding of its causality.Materials and MethodsGSE53987 dataset downloaded from GEO-database, which comprised mRNA expression data of post-mortem brain tissue across three regions from control and age-matched subjects of schizophrenia (N= Hippocampus (HIP): C-15, T-18, Prefrontal cortex (PFC): C-15, T-19, Associative striatum (STR): C-18, T-18). Bio-conductor-affy-package used to compute mRNA expression, and further t-test applied to investigate differential gene expression. The analysis of the derived genes performed using PANTHER Classification System and NCBI database.ResultsA set of 40 genes showed significantly altered (p<0.01) expression across all three brain regions. The analyses unraveled genes implicated in biological processes and events, and molecular pathways relating basic neuronal functions.ConclusionsThe deviant expression of genes maintaining basic cell machinery explains compromised neuronal processing in SCZ.AbbreviationsSchizophrenia (SCZ), Hippocampus (HIP), Associative striatum (STR), Prefrontal cortex (PFC)

scholarly journals Effects of genetics and in utero diet on murine pancreatic development

2014 ◽  
Vol 222 (2) ◽  
pp. 217-227
Author(s):  
Chia-Lei Lin ◽  
Lyda Williams ◽  
Yoshinori Seki ◽  
Harpreet Kaur ◽  
Kirsten Hartil ◽  
...  
Keyword(s):  
Cell Size ◽  
Glucose Transport ◽  
Glucose Transporter ◽  
Control Diet ◽  
Critical Role ◽  
Fold Increase ◽  
Pancreatic Development ◽  
Expression Of Genes ◽  
Health And Disease ◽  
And Function

Intrauterine (IU) malnutrition could alter pancreatic development. In this study, we describe the effects of high-fat diet (HFD) during pregnancy on fetal growth and pancreatic morphology in an ‘at risk’ animal model of metabolic disease, the glucose transporter 4 (GLUT4) heterozygous mouse (G4+/−). WT female mice mated with G4+/− males were fed HFD or control diet (CD) for 2 weeks before mating and throughout pregnancy. At embryonic day 18.5, fetuses were killed and pancreata isolated for analysis of morphology and expression of genes involved in insulin (INS) cell development, proliferation, apoptosis, glucose transport and function. Compared with WT CD, WT HFD fetal pancreata had a 2.4-fold increase in the number of glucagon (GLU) cells (P=0.023). HFD also increased GLU cell size by 18% in WT pancreata compared with WT CD. Compared with WT CD, G4+/− CD had an increased number of INS cells and decreased INS and GLU cell size. Compared with G4+/− CD, G4+/− HFD fetuses had increased pancreatic gene expression ofIgf2, a mitogen and inhibitor of apoptosis. The expression of genes involved in proliferation, apoptosis, glucose transport, and INS secretion was not altered in WT HFD compared with G4+/− HFD pancreata. In contrast to WT HFD pancreata, HFD exposure did not alter pancreatic islet morphology in fetuses with GLUT4 haploinsufficiency; this may be mediated in part by increasedIgf2expression. Thus, interactions between IU diet and fetal genetics may play a critical role in the developmental origins of health and disease.

scholarly journals Overexpression of genes involved in lymphocyte activation and regulation are associated with reduced CRM-derived cardiac remodelling after STEMI

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E De Dios ◽  
C Rios-Navarro ◽  
N Perez-Sole ◽  
J Gavara ◽  
V Marcos-Garces ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Ventricular Function ◽  
Lymphocyte Activation ◽  
Structure And Function ◽  
Cardiac Structure ◽  
Expression Of Genes ◽  
Short And Long Term ◽  
Cardiac Structure And Function ◽  
And Function

Abstract Aims Lymphopenia after ST-segment elevation myocardial infarction (STEMI) correlates with deleterious cardiac consequences and worse prognosis. An in-depth examination of genes implicated in lymphocyte proliferation, activation and regulation and their association with short- and long-term cardiac structure and function is therefore of great interest. Methods Peripheral blood mononuclear cells were isolated from 10 control subjects and 64 patients with a first STEMI treated with primary percutaneous coronary intervention and submitted to cardiac magnetic resonance after 1 week and 6 months. mRNA expression of genes implicated in lymphocyte activation (CD25 and CD69) and regulation [programmed death (PD)-1 and cytotoxic T-lymphocyte antigen (CTLA)-4] were determined by qRT-PCR. Results In comparison to controls, STEMI patients showed heightened mRNA expression of CD25 and lower PD-1 and CTLA-4 96h after coronary reperfusion. Patients with extensive infarctions (&gt;30% of left ventricular mass) at 1 week displayed a notable reduction in CD25, CD69, PD-1, and CTLA-4 expression (p&lt;0.05). However, CD25 was the only predictor of 1-week extensive infarct size in multivariate logistic regression analysis (odds ratio 0.019; 95% confidence interval [0.001–0.505]; p=0.018). Regarding long-term ventricular function, mRNA expression of CD25 under the mean value was associated with worse ventricular function and more adverse remodelling. Conclusions Following STEMI, heightened expression of genes expressed in regulatory T cells (CD25 and CD69) and immune checkpoints (PD-1 and CTLA-4) correlates with a better short- and long-term cardiac structure and function. Advancing understanding of the pathophysiology of lymphopenia and evaluating novel immunomodulatory therapies will help translate these results into future clinical trials. FUNDunding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): “Instituto de Salud Carlos III” and “Fondos Europeos de Desarrollo Regional FEDER”

The microbiota and the gut-brain axis: insights from the temporal and spatial mucosal alterations during colonisation of the germfree mouse intestine

2012 ◽  
Vol 3 (4) ◽  
pp. 251-259 ◽  
Author(s):  
S. El Aidy ◽  
W. Kunze ◽  
J. Bienenstock ◽  
M. Kleerebezem
Keyword(s):  
Nervous System ◽  
Neuronal Development ◽  
Neuronal Response ◽  
Time Resolved ◽  
Altered Expression ◽  
Germfree Mouse ◽  
Plasma Tryptophan ◽  
Expression Of Genes ◽  
Mouse Intestine ◽  
And Function

The influence of the gut microbiota on the nervous system, brain development and behaviour, in particular during microbial colonisation of the host, has recently been receiving profound interest. Our time-resolved mining of combined data analyses of the ex-germfree mouse intestine during a 30-day course of colonisation with conventional mouse faecal microbiota (conventionalisation), shed light on temporal altered expression of genes of which the products influenced functions of the nervous system. Plasma tryptophan and kynurenine levels reflected high indoleamine dioxygenase activity, which was supported by significant temporal induction of the encoding gene in all gut tissues. However, the majority of genes associated with neuronal development and function were reduced. Colonic substance P elevation in response to conventionalisation was higher only after 30-days. These results support a functional microbiota-neurohumoral relationship during conventionalisation and suggest a delayed neuronal response that is elicited only after the microbiota accommodating homeostasis has been accomplished.

scholarly journals Diet alters micronutrient pathways in the gut and placenta that regulate fetal growth and development in pregnant mice

2019 ◽  
Author(s):  
Elia Palladino ◽  
Tim Van Mieghem ◽  
Kristin L. Connor
Keyword(s):  
Mrna Expression ◽  
Fetal Growth ◽  
Relative Abundance ◽  
Folate Receptor ◽  
Control Diet ◽  
Normal Pregnancy ◽  
Micronutrient Deficiencies ◽  
Maternal Malnutrition ◽  
Gut Microbes ◽  
Transporter Protein

AbstractMaternal malnutrition and micronutrient deficiencies can alter fetal development. However, the mechanisms underlying these relationships are poorly understood. We used a systems-physiology approach to investigate diet-induced effects on maternal gut microbes and folate/inositol transport in the maternal/fetal gut and placenta. Female mice were fed a control diet (CON) diet, undernourished (UN, restricted by 30% of CON intake) or a high fat diet (HF, 60% kcals fat) during pregnancy to model normal pregnancy, fetal growth restriction, or maternal metabolic dysfunction, respectively. At gestational day 18.5 we assessed circulating folate levels by microbiological assay, relative abundance of gut lactobacilli by G3PhyloChip™, and folate/inositol transporters in placenta and maternal/fetal gut by qPCR/immunohistochemistry. UN and HF-fed mothers had lower plasma folate concentrations vs. CON. Relative abundance of three lactobacilli taxa were higher in HF vs. UN and CON. HF-fed mothers had higher gut proton coupled folate transporter (Pcft) and reduced folate carrier 1 (Rfc1), and lower sodium myo-inositol co-transporter 2 (Smit2), mRNA expression vs. UN and CON. HF placentae had increased folate receptor beta (Frβ) expression vs. UN. mRNA expression of Pcft, folate receptor alpha (Frα) and Smit2 was higher in gut of HF fetuses vs. UN and CON. Transporter protein expression was not different between groups. Maternal malnutrition alters abundance of select gut microbes and folate/inositol transporters, which may influence maternal micronutrient status and delivery to the fetus, impacting pregnancy/fetal outcomes.

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