Protein Restriction during Pregnancy Induces Hypertension and Impairs Endothelium-Dependent Vascular Function in Adult Female Offspring

Sathishkumar, K.; Elkins, Rebekah; Yallampalli, Uma; Yallampalli, Chandra

doi:10.1159/000166390

Cited by 67 publications

(85 citation statements)

References 109 publications

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“…One of the most extensively studied and well-characterized IUGR models is that of maternal protein restriction in rats, in which the female breeder rats are fed a low-protein diet (6-8.7% casein) from 2 weeks prior to mating until 2 weeks after lactation (Kwong et al, 2000;Sathishkumar et al, 2009). According to the severity of protein restriction, this model has been shown to result in IUGR characterized by a reduction in the body mass of the offspring at birth, with subsequent higher systolic blood pressure, hyperinsulinemia (higher insulin in the bloodstream), hyperleptinemia (higher leptin levels in the bloodstream), abnormal appetite, reduced locomotion, and obesity in the adult offspring (Langley-Evans, Welham & Jackson, 1999;Cheema et al, 2005).…”

Section: (C) Parental Nutrition-induced Epigenetic Inheritancementioning

confidence: 99%

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

2017

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Organisms can change their physiological/behavioural traits to adapt and survive in changed environments. However, whether these acquired traits can be inherited across generations through non-genetic alterations has been a topic of debate for over a century. Emerging evidence indicates that both ancestral and parental experiences, including nutrition, environmental toxins, nurturing behaviour, and social stress, can have powerful effects on the physiological, metabolic and cellular functions in an organism. In certain circumstances, these effects can be transmitted across several generations through epigenetic (i.e. non-DNA sequence-based rather than mutational) modifications. In this review, we summarize recent evidence on epigenetic inheritance from parental environment-induced developmental and physiological alterations in nematodes, fruit flies, zebrafish, rodents, and humans. The epigenetic modifications demonstrated to be both susceptible to modulation by environmental cues and heritable, including DNA methylation, histone modification, and small non-coding RNAs, are also summarized. We particularly focus on evidence that parental environment-induced epigenetic alterations are transmitted through both the maternal and paternal germlines and exert sex-specific effects. The thought-provoking data presented here raise fundamental questions about the mechanisms responsible for these phenomena. In particular, the means that define the specificity of the response to parental experience in the gamete epigenome and that direct the establishment of the specific epigenetic change in the developing embryos, as well as in specific tissues in the descendants, remain obscure and require elucidation. More precise epigenetic assessment at both the genome-wide level and single-cell resolution as well as strategies for breeding at relatively sensitive periods of development and manipulation aimed at specific epigenetic modification are imperative for identifying parental environment-induced epigenetic marks across generations. Considering their diverse epigenetic architectures, the conservation and prevalence of the mechanisms underlying epigenetic inheritance in non-mammals require further investigation in mammals. Interpretation of the consequences arising from epigenetic inheritance on organisms and a better understanding of the underlying mechanisms will provide insight into how gene-environment interactions shape developmental processes and physiological functions, which in turn may have wide-ranging implications for human health, and understanding biological adaptation and evolution.

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Section: (C) Parental Nutrition-induced Epigenetic Inheritancementioning

confidence: 99%

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

2017

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“…Maternal malnutrition can also alter the development of tissue vasculogenesis in the offspring, which may limit beta cell plasticity by disrupting the inductive signals from the microvasculature and an altered presence of endothelial progenitors [34]. Offspring of pregnant rats fed a low-protein diet during gestation exhibit a reduced capillary density in the islets [38]. In summary, nutritional insults can directly impact beta cell plasticity by effects on progenitors and the function of mature beta cells, and may also have indirect effects resulting in impaired trophic signalling between the vascular endothelium and beta cells [39].…”

Section: Prenatal and Neonatal Periodmentioning

confidence: 99%

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Mezza

Kulkarni

2014

Diabetologia

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Regeneration of mature cells that produce functional insulin represents a major focus and a challenge of current diabetes research aimed at restoring beta cell mass in patients with most forms of diabetes, as well as in ageing. The capacity to adapt to diverse physiological states during life and the consequent ability to cope with increased metabolic demands in the normal regulation of glucose homeostasis is a distinctive feature of the endocrine pancreas in mammals. Both beta and alpha cells, and presumably other islet cells, are dynamically regulated via nutrient, neural and/or hormonal activation of growth factor signalling and the post-transcriptional modification of a variety of genes or via the microbiome to continually maintain a balance between regeneration (e.g. proliferation, neogenesis) and apoptosis. Here we review key regulators that determine islet cell mass at different ages in mammals. Understanding the chronobiology and the dynamics and agedependent processes that regulate the relationship between the different cell types in the overall maintenance of an optimally functional islet cell mass could provide important insights into planning therapeutic approaches to counter and/or prevent the development of diabetes.

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“…Offspring of pregnant rats given a LP diet during gestation exhibit a reduction in capillary density in a variety of tissues, including skeletal muscle, endometrium, ovaries and pancreatic islets [5,[72][73][74] . Endothelial dilatation was similarly impaired [75] . Within the pancreas, the number of EPC, characterized as being nestin and CD34-positive, was significantly reduced in offspring of LP-fed mothers [6] , which in other tissues has been associated with a reduced expression of IGF-Ⅱ [76] .…”

Section: Evidence That Early Nutritional Insults Impair β-Cell Regenementioning

confidence: 92%

Nutritional programming of pancreatic β-cell plasticity

Hill

2011

WJD

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Nutritional insufficiency during pregnancy has been shown to alter the metabolism of the offspring and can increase the risk of type 2 diabetes. The phenotype in the offspring involves changes to the morphology and functional capacity of the endocrine pancreas, and in the supporting islet microvasculature. �ancreatic β-cells possess a plastic potential and can partially recover from catastrophic loss. This is partly due to the existence of progenitors within the islets and the ability to generate new islets by neogenesis from the pancreatic ducts. This regenerative capacity is induced by bone marrow-derived stem cells, including endothelial cell progenitors and is associated with increased angiogenesis within the islets. Nutritional insults in early life, such as feeding a low protein diet to the mother, impair the regenerative capacity of the β-cells. The mechanisms underlying this include a reduced ability of β-cells to differentiate from the progenitor population, changes in the inductive signals from the microvasculature and an altered presence of endothelial progenitors. Statin treatment within animal models was associated with angiogenesis in the islet microvasculature, improved vascular function and an increase in β-cell mass. This demonstrates that reversal of the impaired β-cell phenotype observed following nutritional insult in early life is potentially possible.

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Protein Restriction during Pregnancy Induces Hypertension and Impairs Endothelium-Dependent Vascular Function in Adult Female Offspring

Cited by 67 publications

References 109 publications

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

Lamarck rises from his grave: parental environment‐induced epigenetic inheritance in model organisms and humans

The regulation of pre- and post-maturational plasticity of mammalian islet cell mass

Nutritional programming of pancreatic β-cell plasticity

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