scholarly journals Understanding the effects of maternal undernutrition in early gestation on placental development in late gestation

2018 ◽  
Author(s):  
◽  
Gerialisa Allison Marcella Van Gronigen Case
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Maternal Nutrition ◽  
Financial Burden ◽  
Late Gestation ◽  
Placental Development ◽  
Early Gestation ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
The U.S

Chronic diseases such as cardiovascular disease and diabetes are on the rise among the U.S. population. Heart Disease is the leading cause of death in the US and is responsible 610,000 deaths per year. A suite of risk factors for cardiovascular disease and diabetes â€" obesity, elevated blood sugar,hypertension, excess cholesterol, and elevated triglycerides, referred to asMetabolic Syndrome, contributes to an increased risk of mortality. These too areincreasingly prevalent. For example, according to the CDC, in 2011 more than 35% of the U.S. population was obese, with a financial burden of US $147 billion annually. Though improper diet, lack of exercise and socioeconomic status areassociated with these adult diseases, inadequate maternal nutrition just prior toor during pregnancy is also a risk factor. The goal of my research is to identifythe critical time point by which maternal under-nutrition (MUN) during earlygestation permanently alters placental development, the mechanism by whichthis occurs, and whether leptin acts as a mediator.The relationship between the maternal environment and long-term healthof offspring is referred to as the developmental origins of health and disease (DOHaD), or sometimes fetal programming. MUN during pregnancy may affectdeveloping organs to alter the phenotypic outcome of the offspring to promoteadult disease. The timing of the insult is also critical. During the periconceptionalperiod and early gestation, there are major developmental processes such asembryonic organogenesis, and placenta formation. There are also two rounds of DNA methylation reprogramming that occur. I investigated the effects of maternalunder-nutrition from three weeks prior to gestation to d 11.5 (mid gestation inmice). I found that maternal periconceptional food restriction until mid- gestationaffected formation of blood spaces within the labyrinthine placenta near term, ascompared to those from control-fed dams. There was also a three-fold decreasein mRNA encoding SNAT4, an amino acid transporter, in restricted placentae.These changes in placentae from dams fed a nutrient restricted diet suggestsome compensation to ensure adequate nutrients are available to the fetus forproper development.I also examined the effects MUN undernutrition during the first half ofgestation had on placental DNA methylation at late gestation and whether leptinwould act as a mediator of these effects. It is not entirely understood howinformation about maternal nutrition is sensed by the placenta. Leptin, is ahormone that is secreted by fat tissue and plays a role in energy homeostasis,metabolism and reproduction. Therefore, it could be one potential mechanism bywhich maternal nutrition can influence placental function and in turn, fetaldevelopment. I found placentae from dams who experienced MUN and leptinsupplementation had a greater number of differentially methylated regionscompared to placentae from dams fed an adequate fed diet than did placentae ofdams fed MUN only. Regions that were differentially methylated by maternal dietand/or leptin supplementation were located near genes in pathways involved inmolecular transport and carbohydrate metabolism as well as postnatal growth,weight and body size, formation of new blood vessels during embryogenesis. These pathways suggest a link between maternal food deprivation andoffspring's' growth, metabolism and formation of the cardiovascular system.

EFFECTS OF MATERNAL NUTRITION ON THE HUMAN FETUS

PEDIATRICS ◽  
1973 ◽  
Vol 52 (4) ◽  
pp. 494-503
Author(s):  
Richard L. Naeye ◽  
William Blanc ◽  
Cheryl Paul
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Maternal Nutrition ◽  
Cellular Growth ◽  
Late Gestation ◽  
Third Trimester ◽  
Organ Growth ◽  
Maternal Undernutrition ◽  
The Third ◽  
Body Organ

In a study of 467 gestations maternal stature had little correlation with fetal growth but mother's pregravid body weight as well as weight gain and low-calorie diets during pregnancy did have such a correlation. Maternal undernutrition before the third trimester had little or no influence on fetal body, organ, and cellular growth while such effects were pronounced in late gestation. Fetal body and organ growth improved with successive pregnancies except in the most poorly nourished mothers, whose successive neonates became more growth retarded.

scholarly journals Fetal endocrinology and development--manipulation and adaptation to long-term nutritional and environmental challenges

Reproduction ◽  
2001 ◽  
pp. 853-862 ◽  
Author(s):  
ME Symonds ◽  
H Budge ◽  
T Stephenson ◽  
IC McMillen
Keyword(s):  
Adipose Tissue ◽  
Maternal Nutrition ◽  
Uncoupling Protein ◽  
Prolactin Receptor ◽  
Endocrine System ◽  
Adult Obesity ◽  
Maternal Undernutrition ◽  
Increased Risk ◽  
Long Form

This article reviews the fetal endocrine system in sheep, a species that has a long gestation and primarily produces a singleton fetus. Attention is focused on information that is applicable to humans. The endocrinology of metabolic homeostasis in sheep fetuses is well adapted to respond to a range of metabolic challenges, including placental restriction and maternal undernutrition. A small placenta results in hypoxaemia, hypoglycaemia, reduced abundance of anabolic hormones, and fetal growth restriction. Fetuses with restricted growth are characterized by tissue-specific reductions in hormone receptor mRNA, for example mRNA for the long form of prolactin receptor is reduced in adipose tissue. In contrast, the adipose tissue of fetuses with accelerated growth, stimulated by increasing maternal nutrition in the second half of gestation, has more protein for the long form of the prolactin receptor and more uncoupling protein 1, by which large amounts of heat are generated at birth. Maternal undernutrition in early gestation, coinciding with the period of rapid placental growth, initially restricts placental growth, but when mothers are fed to requirements, a longer fetus results with a disproportionately large placenta. This nutritional manipulation replicates, in part, epidemiological findings from the Dutch famine of 1944-1945, for which the offspring are at increased risk of adult obesity.

scholarly journals Abnormal lipid metabolism in metabolic syndrome: an epigenetic perspective

2016 ◽  
Vol 24 (2) ◽  
pp. 153-160 ◽  
Author(s):  
Ioana Brudașcă ◽  
Mircea Cucuianu
Keyword(s):  
Metabolic Syndrome ◽  
Dna Methylation ◽  
Life Span ◽  
Maternal Obesity ◽  
Maternal Nutrition ◽  
Hdl Cholesterol ◽  
Atherogenic Dyslipidemia ◽  
Epigenetic Changes ◽  
The Metabolic Syndrome ◽  
Increased Risk

Abstract Metabolic syndrome is a complex pathology including central obesity, impaired glucose tolerance/diabetes, an atherogenic dyslipidemia and a prothrombotic state. A new perspective on understanding the mechanisms underlying metabolic syndrome is provided by the epigenetic changes (mainly DNA methylation and histone covalent modifications), which influence gene expression without changing of the DNA sequence. DNA methylation (mainly in carnitine palmitoyltransferase 1A gene) and histone modifications were shown to be associated with VLDL and LDL phenotypes, with hyperglycemia and reduced level of HDL cholesterol, with hypertriglyceridemic waist phenotype and with progression of atherosclerotic occlusion in peripheral arteries. The epigenetic changes can occur in the prenatal period, throughout the life span, and can be transmitted to the offspring. Both poor maternal nutrition and maternal obesity, diabetes and overfeeding can result in epigenetic alterations that amplify the risk of metabolic syndrome for the offspring. Throughout life span, environmental factors, such as nutrition and exercise can induce epigenetic changes influencing the evolution of the metabolic syndrome (through adipocyte metabolism and insulin signaling pathway). The epigenetic modifications are not completely erased during gametogenesis and embryogensis, resulting in a transgenerational transmission of an epigenetic state up to the fifth generation. Epigenetic mechanisms are an interface between environmental stimuli and resulting phenotype by inducing a certain transcriptional state, which may be also transmitted to the next generation(s) and which may predispose to an increased risk for developing metabolic syndrome in the context of a mismatched environment. Elucidating epigenetic modulation might provide additional information about risk evaluation and more targeted therapeutical intervention.

scholarly journals Prenatal Synthetic Glucocorticoid Treatment Changes DNA Methylation States in Male Organ Systems: Multigenerational Effects

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3269-3283 ◽  
Author(s):  
Ariann Crudo ◽  
Sophie Petropoulos ◽  
Vasilis G. Moisiadis ◽  
Majid Iqbal ◽  
Alisa Kostaki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Critical Role ◽  
Covalent Modification ◽  
Late Gestation ◽  
Next Generation ◽  
Long Term Effects ◽  
Glucocorticoid Treatment ◽  
Epigenetic State ◽  
Organ Systems ◽  
Increased Risk

Prenatal synthetic glucocorticoids (sGC) are administered to pregnant women at risk of delivering preterm, approximately 10% of all pregnancies. Animal studies have demonstrated that offspring exposed to elevated glucocorticoids, either by administration of sGC or as a result of maternal stress, are at increased risk of developing behavioral, endocrine, and metabolic abnormalities. DNA methylation is a covalent modification of DNA that plays a critical role in long-lasting programming of gene expression. Here we tested the hypothesis that prenatal sGC treatment has both acute and long-term effects on DNA methylation states in the fetus and offspring and that these effects extend into a subsequent generation. Pregnant guinea pigs were treated with sGC in late gestation, and methylation analysis by luminometric methylation assay was undertaken in organs from fetuses and offspring across two generations. Expression of genes that modify the epigenetic state were measured by quantitative real-time PCR. Results indicate that there are organ-specific developmental trajectories of methylation in the fetus and newborn. Furthermore, these trajectories are substantially modified by intrauterine exposure to sGC. These sGC-induced changes in DNA methylation remain into adulthood and are evident in the next generation. Furthermore, prenatal sGC exposure alters the expression of several genes encoding proteins that modulate the epigenetic state. Several of these changes are long lasting and are also present in the next generation. These data support the hypothesis that prenatal sGC exposure leads to broad changes in critical components of the epigenetic machinery and that these effects can pass to the next generation.

159. MATERNAL NUTRITION AND GESTATIONAL AGE AFFECT PLACENTAL microRNA EXPRESSION IN THE GUINEA PIG

2009 ◽  
Vol 21 (9) ◽  
pp. 77
Author(s):  
P. A. Grant ◽  
K. L. Kind ◽  
A. Sohlstrom ◽  
C. T. Roberts ◽  
J. A. Owens
Keyword(s):  
Guinea Pig ◽  
Guinea Pigs ◽  
Target Genes ◽  
Microrna Expression ◽  
Late Gestation ◽  
Altered Expression ◽  
Early Gestation ◽  
Maternal Undernutrition ◽  
Guinea Pig Placenta ◽  
Pig Placenta

Maternal undernutrition restricts placental growth and nutrient supply to the fetus, but induces compensatory alterations in structure and function of the placenta. Maternal undernutrition in guinea pigs also restricts placental growth and alters structure, and changes expression of Igf1, Igf2, Slc2a1, Slc38a2 mRNA in mid and late gestation, consistent with nutritionally induced changes in nutrient transport across the placenta. MicroRNAs are non-coding RNAs that regulate expression of target genes by translational inhibition and mRNA degradation and are present in the mammalian placenta. Effects of maternal undernutrition on their expression are unknown. We hypothesised that altered expression of key functional genes in the placenta in maternal undernutrition are in part due to altered expression of regulatory microRNAs. The effect of maternal food restriction on the expression of microRNAs in the guinea pig placenta was examined at D30 and D60 of gestation (term = D70). Guinea pigs were fed either ad libitum (AL) or restricted (R). MicroRNA expression was determined by Exiqon microarray v.8.1. In AL placentas, 119 microRNAs were upregulated (p<0.05), whilst 40 were down-regulated (p<0.05) at late compared to early gestation. In R placentas, 163 microRNAs were upregulated (p<0.05), whilst 123 were down-regulated (p<0.05) at late compared to early gestation. Of the 20 most abundant up-regulated microRNAs miR-Plus (ID 17871) and hsa-miR-411 were altered only in AL and hsa-miR-376a and -376b were altered only in R placenta. Of the 20 most abundant down-regulated microRNAs, 13 were altered only in AL and 14 only in R placentas. Placental expression of microRNAs changed with gestation, and maternal undernutrition modified this pattern and altered expression of many additional microRNAs in the guinea pig placenta. This suggests that miRNAs and factors that influence their expression may play a role in the structural and/or functional development of the placenta and hence fetal growth.

010. PERICONCEPTIONAL UNDERNUTRITION: LIFE-LONG EFFECTS FOR THE OFFSPRING

2010 ◽  
Vol 22 (9) ◽  
pp. 6
Author(s):  
F. H. Bloomfield ◽  
M. H. Oliver ◽  
A. L. Jaquiery ◽  
C. Hernandez ◽  
J. R. G. Challis ◽  
...  
Keyword(s):  
Maternal Nutrition ◽  
Late Gestation ◽  
Critical Window ◽  
Maternal Undernutrition ◽  
Maternal Nutritional Status ◽  
Child Bearing ◽  
Offspring Sex ◽  
Periconceptional Period ◽  
Altered Response ◽  
Poor Nutrition

Poor nutrition in women of child-bearing age is common, even in Western countries. It has been estimated that approximately 30% of women of child-bearing age in affluent cities such as Sydney and Southampton are either actively dieting or have a nutritional intake that does not meet daily recommended requirements for all nutrients. We have investigated the effect of reduced maternal nutrition before and around the time of conception on fetal growth and development, and have followed offspring through to adulthood. In this paradigm, ewes were fed to lose 10–15% of their body weight and then to gain weight according to conceptus mass. Control ewes were well fed throughout. Different timing and duration of undernutrition in the periconceptional period were utilised to investigate the most critical window for fetal development. Periconceptional undernutrition resulted in accelerated development of the fetal hypothalamic-pituitary-adrenal (HPA) and glucose-insulin axes in late gestation, and preterm birth. Offspring of periconceptionally undernourished ewes demonstrated altered laterality and an altered response to isolation stress; HPA axis function was also suppressed. As offspring aged, glucose tolerance decreased and became significantly impaired by young adulthood compared with control offspring. The effects of maternal undernutrition on offspring were modified by offspring sex and also by being one of a twin pair. Interestingly, our data also demonstrate that conception as a twin, regardless of maternal nutritional status, also affects all these outcomes but in a different way to maternal undernutrition. Preliminary data suggest that epigenetic changes in feeding centres of the hypothalamus may play a role in the mechanism behind some of these effects. These studies suggest that even moderate maternal undernutrition in very early pregnancy has life-long effects. Should this also be true in humans, then health care messages for women may need to be targeted prior to pregnancy.

scholarly journals The effect of maternal undernutrition on ovine fetal growth

2002 ◽  
Vol 173 (1) ◽  
pp. 131-141 ◽  
Author(s):  
JC Osgerby ◽  
DC Wathes ◽  
D Howard ◽  
TS Gadd
Keyword(s):  
Fetal Growth ◽  
Bone Growth ◽  
Maternal Nutrition ◽  
Fetal Brain ◽  
Late Gestation ◽  
Adult Health ◽  
Semitendinosus Muscle ◽  
Fetal Plasma ◽  
Maternal Undernutrition ◽  
Igf I

Modifications in maternal nutrition during pregnancy can significantly disrupt fetal growth and subsequent post-natal health and survival. This study investigated the effects of undernutrition on fetal growth and the potential mechanisms involved. Tissue from pregnant ewes (n=27) was investigated on days 45, 90 and 135 of gestation (term = approximately 150 days). The thoracic girth (P<0.05) was greater in fetuses from nutrient restricted ewes on day 45 and there was also a trend towards an increased gut weight (P<0.08). By day 90, the fetal brain and thymus weight were lighter in underfed than in well-fed animals whilst the weight of the fetal ovaries was heavier (P<0.05). On day 135 the fetal heart, pancreas, thymus, gut and kidney weights were lighter in undernourished ewes (P<0.05). When expressed as a percentage of fetal body weight, significance was retained in the heart, pancreas and thymus (P<0.05). Bone growth was also affected. At day 90 the fetal femur and metatarsal were longer in underfed mothers (P<0.05). In contrast, the fetal humerus and scapula were shorter in underfed than in well-fed animals on day 135 (P<0.05) when the weight of the semitendinosus muscle (P<0.05) was also reduced. The fall in fetal glucose (P<0.1), insulin (P<0.01) and IGF-I (P<0.01) levels in underfed ewes on day 135 may have compromised fetal growth. Fetal plasma IGF binding protein-2 also increased between days 90 and 135 in underfed ewes (P<0.03), whilst levels were unaltered in well-fed animals. Although maternal and fetal plasma IGF-I levels increased with gestation (P<0.01) and the placentome morphology altered in all ewes (P<0.05), the fall in placental mass (P<0.05), amniotic and allantoic glucose concentrations (P<0.05) and maternal plasma glucose and insulin levels (P<0.05) in underfed ewes in late gestation may have compromised fetal substrate delivery. These perturbations in fetal development may have significant implications on adult health and carcass conformation, raising important health and economic issues in medical and agricultural sectors.

scholarly journals Clinical applicability of methylome sequencing in a pilot study of ischemic stroke individuals

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Mark Ziemann ◽  
KN Harikrishnan ◽  
Ishant Khurana ◽  
Antony Kaspi ◽  
Samuel T Keating ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Dna Methylation ◽  
Ischemic Stroke ◽  
Association Studies ◽  
Clinical Samples ◽  
Genome Wide Association Studies ◽  
Disease Etiology ◽  
Clinical Applicability ◽  
Genome Wide ◽  
Increased Risk

Abstract Despite recent progress in screening for genetic causes of cardiovascular disease using genome-wide association studies, identifying causative polymorphisms has not met initial expectations. This has led to interest in exploring the contribution of non-genetic factors in disease etiology. Elevated plasma homocysteine is an independent risk factor for cardiovascular disease but the mechanism for increased risk remains poorly understood. This study evaluates the clinical applicability of screening for genome-wide CpG methylation differences using methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq). Peripheral blood genomic DNA methylation in 8 Singaporean-Chinese ischemic stroke patients (4 male, 4 female) was profiled. Differential methylation of genes implicated in hyperhomocysteinemia was observed in males correlating with homocysteine; namely CBS (cystathionine-beta-synthase) and MTHFR (methylenetetrahydrofolate reductase). In females, hypomethylation of the LDLR (low density lipoprotein receptor) and CELSR1 (cadherin, EGF LAG seven-pass G-type receptor 1) genes were observed in the hypertensive group (2 normal and 2 hypertensive individuals). While the number of clinical samples analysed is small, the findings of this evaluation suggest that MBD-seq is a suitable and sufficiently sensitive technology to determine methylation variability. The results presented warrant an expanded case-control study to determine the pathophysiological implications of DNA methylation for hyper-homocysteinemia.

scholarly journals Glucocorticoid Programming of the Fetal Male Hippocampal Epigenome

Endocrinology ◽  
2013 ◽  
Vol 154 (3) ◽  
pp. 1168-1180 ◽  
Author(s):  
Ariann Crudo ◽  
Matthew Suderman ◽  
Vasilis G. Moisiadis ◽  
Sophie Petropoulos ◽  
Alisa Kostaki ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Promoter Methylation ◽  
Plasma Cortisol ◽  
Late Gestation ◽  
Gene Promoters ◽  
Fetal Plasma ◽  
Genome Wide ◽  
Organ Systems ◽  
Increased Risk ◽  
H3k9 Acetylation

Abstract The late-gestation surge in fetal plasma cortisol is critical for maturation of fetal organ systems. As a result, synthetic glucocorticoids (sGCs) are administered to pregnant women at risk of delivering preterm. However, animal studies have shown that fetal exposure to sGC results in increased risk of behavioral, endocrine, and metabolic abnormalities in offspring. Here, we test the hypothesis that prenatal GC exposure resulting from the fetal cortisol surge or after sGC exposure results in promoter-specific epigenetic changes in the hippocampus. Fetal guinea pig hippocampi were collected before (gestational day [GD52]) and after (GD65) the fetal plasma cortisol surge (Term∼GD67) and 24 hours after (GD52) and 14 days after (GD65) two repeat courses of maternal sGC (betamethasone) treatment (n = 3–4/gp). We identified extensive genome-wide alterations in promoter methylation in late fetal development (coincident with the fetal cortisol surge), whereby the majority of the affected promoters exhibited hypomethylation. Fetuses exposed to sGC in late gestation exhibited substantial differences in DNA methylation and histone h3 lysine 9 (H3K9) acetylation in specific gene promoters; 24 hours after the sGC treatment, the majority of genes affected were hypomethylated or hyperacetylated. However, 14 days after sGC exposure these differences did not persist, whereas other promoters became hypermethylated or hyperacetylated. These data support the hypothesis that the fetal GC surge is responsible, in part, for significant variations in genome-wide promoter methylation and that prenatal sGC treatment profoundly changes the epigenetic landscape, affecting both DNA methylation and H3K9 acetylation. This is important given the widespread use of sGC in the management of women in preterm labor.

Impact of maternal undernutrition on diabetes and cardiovascular disease risk in adult offspring

2009 ◽  
Vol 87 (3) ◽  
pp. 161-179 ◽  
Author(s):  
Caroline Le Clair ◽  
Tina Abbi ◽  
Heather Sandhu ◽  
Paramjit S. Tappia
Keyword(s):  
Cardiovascular Disease ◽  
Birth Weight ◽  
Low Birth Weight ◽  
Maternal Nutrition ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Adult Life ◽  
Adult Disease ◽  
Maternal Undernutrition ◽  
The Impact

Epidemiological, clinical, and experimental observations have led to the hypothesis that the risk of developing chronic diseases in adulthood is influenced not only by genetic and adult lifestyle factors, but also by environmental factors during early life. Low birth weight, a marker of intrauterine stress, has been linked to predisposition to cardiovascular disease (CVD) and diabetes. The compelling animal evidence and significant human data to support this conclusion are reviewed. Specifically, the review discusses the role of maternal nutrition before and during pregnancy, placental insufficiencies and epigenetic changes in the increased predisposition to diabetes and CVD in adult life. The impact of low birth weight and catch-up growth as they pertain to risk of disease in adult life is also discussed. In addition, adult disease risk in the overnourished fetus is also mentioned. Reference is made to some of the mechanisms of the induction of diabetes and CVD phenotype. It is proposed that fetal nutrition, growth and development through efficient maternal nutrition before and during pregnancy could constitute the basis for nutritional strategies for the primary prevention of diabetes and CVD.

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