scholarly journals Epigenetics in the Uterine Environment: How Maternal Diet and ART May Influence the Epigenome in the Offspring with Long-Term Health Consequences

Genes ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 31
Author(s):  
Irene Peral-Sanchez ◽  
Batoul Hojeij ◽  
Diego A. Ojeda ◽  
Régine P. M. Steegers-Theunissen ◽  
Sandrine Willaime-Morawek
Keyword(s):  
Target Genes ◽  
Communicable Disease ◽  
Maternal Diet ◽  
Epigenetic Modifications ◽  
Maternal Undernutrition ◽  
Supplement Use ◽  
Maternal Nutritional Status ◽  
Low Protein ◽  
Uterine Environment ◽  
The Life Course

The societal burden of non-communicable disease is closely linked with environmental exposures and lifestyle behaviours, including the adherence to a poor maternal diet from the earliest preimplantation period of the life course onwards. Epigenetic variations caused by a compromised maternal nutritional status can affect embryonic development. This review summarises the main epigenetic modifications in mammals, especially DNA methylation, histone modifications, and ncRNA. These epigenetic changes can compromise the health of the offspring later in life. We discuss different types of nutritional stressors in human and animal models, such as maternal undernutrition, seasonal diets, low-protein diet, high-fat diet, and synthetic folic acid supplement use, and how these nutritional exposures epigenetically affect target genes and their outcomes. In addition, we review the concept of thrifty genes during the preimplantation period, and some examples that relate to epigenetic change and diet. Finally, we discuss different examples of maternal diets, their effect on outcomes, and their relationship with assisted reproductive technology (ART), including their implications on epigenetic modifications.

scholarly journals Body composition and behaviour in adult rats are influenced by maternal diet, maternal age and high-fat feeding

2015 ◽  
Vol 4 ◽  
Author(s):  
S. Ware ◽  
J.-P. Voigt ◽  
S. C. Langley-Evans
Keyword(s):  
Body Composition ◽  
Weight Gain ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Maternal Age ◽  
Maternal Diet ◽  
High Fat ◽  
Older Mothers ◽  
Maternal Undernutrition ◽  
Low Protein

AbstractFetal exposure to maternal undernutrition has lifelong consequences for physiological and metabolic function. Maternal low-protein diet is associated with an age-related phenotype in rats, characterised by a period of resistance to development of obesity in early adulthood, giving way to an obesity-prone, insulin-resistant state in later adulthood. Offspring of rats fed a control (18 % casein) or low-protein (9 % casein; LP) diet in pregnancy were challenged with a high-fat diet at 9 months of age. To assess whether other maternal factors modulated the programming effects of nutrition, offspring were studied from young (2–4 months old) and older (6–9 months old) mothers. Weight gain with a high-fat diet was attenuated in male offspring of older mothers fed LP (interaction of maternal age and diet; P = 0·011) and adipose tissue deposition was lower with LP feeding in both males and females (P < 0·05). Although the resistance to weight gain and adiposity was partially explained by lower energy intake in offspring of LP mothers (P < 0·001 males only), it was apparent that energy expenditure must be influenced by maternal diet and age. Assessment of locomotor activity indicated that energy expenditure associated with physical activity was unlikely to explain resistance to weight gain, but showed that offspring of older mothers were more anxious than those of younger mothers, with more rearing observed in a novel environment and on the elevated plus-maze. The data showed that in addition to maternal undernutrition, greater maternal age may influence development and long-term body composition in the rat.

scholarly journals Maternal low protein diet programmes low ovarian reserve in offspring

Reproduction ◽  
2018 ◽  
Author(s):  
Amy L Winship ◽  
Sarah E Gazzard ◽  
Luise A Cullen McEwen ◽  
John F Bertram ◽  
Karla J Hutt
Keyword(s):  
Ovarian Reserve ◽  
Histological Analysis ◽  
Maternal Diet ◽  
Primordial Follicle ◽  
In Utero ◽  
Primordial Follicles ◽  
Maternal Undernutrition ◽  
Low Protein ◽  
Pregnancy And Lactation ◽  
In Utero Development

The ovarian reserve of primordial follicle oocytes is formed during in utero development and represents the entire supply of oocytes available to sustain female fertility. Maternal undernutrition during pregnancy and lactation diminishes offspring ovarian reserve in rats. In mice, maternal oocyte maturation is also susceptible to undernutrition, causing impaired offspring cardiovascular function. We aimed to determine whether programming of the ovarian reserve is impacted in offspring when maternal undernutrition extends from preconception oocyte development through to weaning. C57BL6/J female mice were fed normal protein (20%) or low protein (8%) diet during preconception, pregnancy and lactation periods. Maternal ovaries were harvested at weaning and offspring ovaries collected at postnatal day (PN)21 and 24 weeks of age. Total follicle estimates were obtained by histologically sampling one ovary per animal (n=5/group). There was no impact of diet on maternal follicle numbers. However, in offspring, maternal protein restriction significantly depleted primordial follicles by 37% at PN21 and 51% at 24 weeks (p<0.05). There were no effects of diet on other follicle classes. Histological analysis showed no differences in the proportion of proliferative follicles (pH3-positive), but increased atresia (cleaved caspase-3-positive, or TUNEL-positive) was detected in ovaries of protein-restricted offspring at both ages (p<0.05). Our data show that maternal diet during the preconception period, in utero development and early life has significant impacts on follicle endowment and markers of follicle health later in life. This highlights the need for further investigation into the importance of maternal preconception diet for offspring reproductive development and health.

scholarly journals The influence of maternal protein nutrition on offspring development and metabolism: the role of glucocorticoids

2011 ◽  
Vol 71 (1) ◽  
pp. 198-203 ◽  
Author(s):  
K. Almond ◽  
P. Bikker ◽  
M. Lomax ◽  
M. E. Symonds ◽  
A. Mostyn
Keyword(s):  
Maternal Diet ◽  
Protein Supplementation ◽  
Maternal Environment ◽  
Maternal Undernutrition ◽  
Low Protein ◽  
Increased Risk ◽  
Neonatal Body Composition ◽  
Tissue Sensitivity ◽  
Protein Diets

The consequences of sub-optimal nutrition through alterations in the macronutrient content of the maternal diet will not simply be reflected in altered neonatal body composition and increased mortality, but are likely to continue into adulthood and confer greater risk of metabolic disease. One mechanism linking manipulations of the maternal environment to an increased risk of later disease is enhanced fetal exposure to glucocorticoids (GC). Tissue sensitivity to cortisol is regulated, in part, by the GC receptor and 11β-hydroxysteroid dehydrogenase (11β-HSD) types 1 and 2. Several studies have shown the effects of maternal undernutrition, particularly low-protein diets, on the programming of GC action in the offspring; however, dietary excess is far more characteristic of the diets consumed by contemporary pregnant women. This study investigated the programming effects of moderate protein supplementation in pigs throughout pregnancy. We have demonstrated an up-regulation of genes involved in GC sensitivity, such as GC receptor and 11β-HSD, in the liver, but have yet to detect any other significant changes in these piglets, with no differences observed in body weight or composition. This increase in GC sensitivity was similar to the programming effects observed following maternal protein restriction or global undernutrition during pregnancy.

scholarly journals Fetal programming of cardiovascular function through exposure to maternal undernutrition

2001 ◽  
Vol 60 (4) ◽  
pp. 505-513 ◽  
Author(s):  
Simon C. Langley-Evans
Keyword(s):  
Disease Risk ◽  
Birth Outcome ◽  
Communicable Disease ◽  
Cardiovascular Disease Risk ◽  
Experimental Studies ◽  
Cardiovascular Function ◽  
Postnatal Life ◽  
Maternal Undernutrition ◽  
Low Protein ◽  
Protein Diets

A substantial and robust body of epidemiological evidence indicates that prenatal dietary experience may be a factor determining cardiovascular disease risk. Retrospective cohort studies indicate that low birth weight and disproportion at birth are powerful predictors of later disease risk. This prenatal influence on non-communicable disease in later life has been termed programming. Maternal nutritional status has been proposed to be the major programming influence on the developing fetus. The evidence from epidemiological studies of nutrition, fetal development and birth outcome is, however, often weak and inconclusive. The validity of the nutritional programming concept is highly dependent on experimental studies in animals. The feeding of low-protein diets in rat pregnancy results in perturbations in fetal growth and dimensions at birth. The offspring of rats fed low-protein diets exhibit a number of metabolic and physiological disturbances, and are consistently found to have high blood pressure from early postnatal life. This experimental model has been used to explore potential mechanisms of programming through which maternal diet may programme the cardiovascular function of the fetus. Indications from this work are that fetal exposure to maternally-derived glucocorticoids plays a key role in the programming mechanism. Secondary to this activity, the fetal hypothalamic–pituitary–adrenal axis may stimulate renin–angiotensin system activity, resulting in increased vascular resistance and hypertension.

scholarly journals Gestational Low Protein Diet Modulation on miRNA Transcriptome and Its Target During Fetal and Breastfeeding Nephrogenesis

2021 ◽  
Vol 12 ◽  
Author(s):  
Letícia de Barros Sene ◽  
Gabriela Leme Lamana ◽  
Andre Schwambach Vieira ◽  
Wellerson Rodrigo Scarano ◽  
José Antônio Rocha Gontijo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Progenitor Cells ◽  
Target Genes ◽  
Maternal Diet ◽  
Protein Restriction ◽  
Protein Diet ◽  
Compensatory Mechanisms ◽  
Adult Age ◽  
Renal Progenitor Cells ◽  
Low Protein

BackgroundThe kidney ontogenesis is the most structurally affected by gestational protein restriction, reducing 28% of their functional units. The reduced nephron number is predictive of hypertension and cardiovascular dysfunctions that are generally observed in the adult age of most fetal programming models. We demonstrate miRNAs and predict molecular pathway changes associated with reduced reciprocal interaction between metanephros cap (CM) and ureter bud (UB) and a 28% decreased nephron stem cells in the 17 gestational days (17GD) low protein (LP) intake male fetal kidney. Here, we evaluated the same miRNAs and predicted targets in the kidneys of 21GD and at 7 days of life (7DL) LP offspring to elucidate the molecular modulations during nephrogenesis.MethodsPregnant Wistar rats were allocated into two groups: NP (regular protein diet- 17%) or LP (diet-6%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform from 21GD and 7DL male offspring kidneys using previously described methods. Among the top 10 dysfunctional regulated miRNAs, we validated 7 related to proliferation, differentiation, and apoptosis processes and investigated predicted target genes and proteins by RT-qPCR and immunohistochemistry.ResultsIn 21GD, LP fetuses were identified alongside 21 differently expressed miRNAs, of which 12 were upregulated and 9 downregulated compared to age-matched NP offspring. In 7-DL LP offspring, the differentially expressed miRNAs were counted to be 74, of which 46 were upregulated and 28 downregulated. The curve from 17-GD to 7-DL shows that mTOR was fundamental in reducing the number of nephrons in fetal kidneys where the mothers were subjected to a protein restriction. IGF1 and TGFβ curves also seemed to present the same mTOR pattern and were modulated by miRNAs 181a-5p, 181a-3p, and 199a-5p. The miRNA 181c-3p modulated SIX2 and Notch1 reduction in 7-DL but not in terms of the enhanced expression of both in the 21-GD, suggesting the participation of an additional regulator. We found enhanced Bax in 21-GD; it was regulated by miRNA 298-5p, and Bcl2 and Caspase-3 were controlled by miRNA (by 7a-5p and not by the predicted 181a-5p). The miRNA 144-3p regulated BCL6, which was enhanced, as well as Zeb 1 and 2 induced by BCL6. These results revealed that in 21GD, the compensatory mechanisms in LP kidneys led to the activation of UB ramification. Besides, an increase of 32% in the CM stem cells and a possible cell cycle halt of renal progenitor cells, which remaining undifferentiated, were observed. In the 7DL, much more altered miRNA expression was found in LP kidneys, and this was probably due to an increased maternal diet content. Additionally, we verified the activation of pathways related to differentiation and consumption of progenitor cells.

scholarly journals Maternal micronutrient consumption periconceptionally and during pregnancy: a prospective cohort study

2016 ◽  
Vol 20 (2) ◽  
pp. 294-304 ◽  
Author(s):  
Michelle Livock ◽  
Peter J Anderson ◽  
Sharon Lewis ◽  
Stephen Bowden ◽  
Evelyne Muggli ◽  
...  
Keyword(s):  
Cohort Study ◽  
Prospective Cohort Study ◽  
Repeated Measures ◽  
Prospective Cohort ◽  
Tertiary Education ◽  
Maternal Diet ◽  
Daily Intake ◽  
Public Health Education ◽  
Singleton Pregnancy ◽  
Supplement Use

AbstractObjectiveTo examine overall micronutrient intake periconceptionally and throughout pregnancy in a population-based cohort of Australian women.DesignIn a prospective cohort study, micronutrient dosages were extracted from self-reported maternal supplement use, recorded pre-conception, and for each trimester of pregnancy. A food frequency scale (DQESv2) captured usual maternal diet for gestational weeks 14–26. The influence of sociodemographic and lifestyle factors associated with supplement use was examined using logistic regression, and changes in micronutrient intakes prior to and throughout pregnancy were assessed using repeated-measures ANOVA analyses.SettingMetropolitan hospital sites in Melbourne, Australia.SubjectsWomen with a viable singleton pregnancy were recruited at less than 19 weeks’ gestation (n2146).ResultsCompared with non-users, women using supplements during pregnancy were more likely to have planned their pregnancy, be >25 years old, primiparous, Caucasian, non-smokers, have a tertiary education and be consuming a folate-rich diet. Intakes of folate, Fe and Zn were significantly lower in the periconceptional period, compared with other periods (P<0·001). Intakes below Recommended Daily Intake levels were common both periconceptionally and throughout pregnancy, with 19–46 % of women not meeting the Recommended Daily Intake for folate, 68–82 % for Fe and 17–36 % for Zn. Conversely, 15–19 % of women consumed beyond the recommended Upper Limit for folate and 11–24 % for Fe.ConclusionsThe study highlights the need for improved public health education on nutritional needs during pregnancy, especially among women with lower educational achievements and income.

Maternal undernutrition reduces aortic wall thickness and elastin content in offspring rats without altering endothelial function

2006 ◽  
Vol 111 (4) ◽  
pp. 281-287 ◽  
Author(s):  
Michael R. Skilton ◽  
Alison K. Gosby ◽  
Ben J. Wu ◽  
Lisa M. L. Ho ◽  
Roland Stocker ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Aortic Wall ◽  
Infant Nutrition ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Organ Bath ◽  
High Fat ◽  
Maternal Undernutrition ◽  
Low Protein ◽  
Aortic Wall Thickness

Epidemiological studies suggest a link between fetal/early infant nutrition and adult coronary artery disease. In the present study, we examined the effects of altering nutrition during gestation, lactation and juvenile life on aortic structure and function in rats. Wistar rat dams were fed either a control or low-protein diet throughout pregnancy, or a low-protein diet for the final 7 days of gestation only. At 21 days post-partum, male pups were weaned on to a control, low-protein or high-fat diet. At 12 weeks, the offspring rats were killed. In 46 rats, aortic sections were mounted and stained to assess media thickness and elastin content. In a further 38 rats, aortic rings were suspended in an organ bath and vascular reactivity was tested with dose–response curves to the endothelium-dependent dilator acetylcholine and the endothelium-independent dilator sodium nitroprusside. Rats exposed to maternal protein restriction while in utero had a significantly decreased aortic wall thickness compared with control rats (P=0.005). Total elastin content of the aorta was also decreased by both maternal low-protein (P=0.02) and early postnatal low-protein (P=0.01) diets. Neither maternal nor postnatal low-protein or high-fat diets, however, resulted in any significant changes in arterial dilator function. In conclusion, fetal undernutrition in rats, induced via a maternal low-protein diet, causes a decrease in aortic wall thickness and elastin content without altering aortic dilator function. These changes in vascular structure may amplify aging-related changes to the vasculature and contribute to the pathophysiology of the putative link between impaired fetal growth and adult cardiovascular disease.

Offspring’s hydromineral adaptive responses to maternal undernutrition during lactation

2015 ◽  
Vol 6 (6) ◽  
pp. 520-529 ◽  
Author(s):  
P. Nuñez ◽  
J. Arguelles ◽  
C. Perillan
Keyword(s):  
Salt Intake ◽  
Maternal Diet ◽  
Plasma Osmolality ◽  
Control Mechanisms ◽  
Lactation Period ◽  
Adaptive Responses ◽  
Long Term Effects ◽  
Molecular Alterations ◽  
Maternal Undernutrition ◽  
Renal Histology

Early development, throughout gestation and lactation, represents a period of extreme vulnerability during which susceptibility to later metabolic and cardiovascular injuries increases. Maternal diet is a major determinant of the foetal and newborn developmental environment; maternal undernutrition may result in adaptive responses leading to structural and molecular alterations in various organs and tissues, such as the brain and kidney. New nephron anlages appear in the renal cortex up to postnatal day 4 and the last anlages to be formed develop into functional nephrons by postnatal day 10 in rodents. We used a model of undernutrition in rat dams that were food-restricted during the first half of the lactation period in order to study the long-term effects of maternal diet on renal development, behaviour and neural hydromineral control mechanisms. The study showed that after 40% food restriction in maternal dietary intake, the dipsogenic responses for both water and salt intake were not altered; Fos expression in brain areas investigated involved in hydromineral homeostasis control was always higher in the offspring in response to isoproterenol. This was accompanied by normal plasma osmolality changes and typical renal histology. These results suggest that the mechanisms for the control of hydromineral balance were unaffected in the offspring of these 40% food-restricted mothers. Undernutrition of the pups may not be as drastic as suggested by dams’ restriction.

scholarly journals Consequences of Paternal Nutrition on Offspring Health and Disease

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2818
Author(s):  
Pauline Dimofski ◽  
David Meyre ◽  
Natacha Dreumont ◽  
Brigitte Leininger-Muller
Keyword(s):  
Metabolic Pathways ◽  
Maternal Diet ◽  
Disease Onset ◽  
Adult Life ◽  
Intermittent Fasting ◽  
Low Protein ◽  
Periconceptional Period ◽  
Health And Disease ◽  
Offspring Health ◽  
The Impact

It is well established that the maternal diet during the periconceptional period affects the progeny’s health. A growing body of evidence suggests that the paternal diet also influences disease onset in offspring. For many years, sperm was considered only to contribute half of the progeny’s genome. It now appears that it also plays a crucial role in health and disease in offspring’s adult life. The nutritional status and environmental exposure of fathers during their childhood and/or the periconceptional period have significant transgenerational consequences. This review aims to describe the effects of various human and rodent paternal feeding patterns on progeny’s metabolism and health, including fasting or intermittent fasting, low-protein and folic acid deficient food, and overnutrition in high-fat and high-sugar diets. The impact on pregnancy outcome, metabolic pathways, and chronic disease onset will be described. The biological and epigenetic mechanisms underlying the transmission from fathers to their progeny will be discussed. All these data provide evidence of the impact of paternal nutrition on progeny health which could lead to preventive diet recommendations for future fathers.

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