Regulation of growth and metabolism by imprinted genes

Smith, Florentia M.; Garfield, Alastair S.; Ward, Andrew

doi:10.1159/000090843

Cited by 175 publications

(122 citation statements)

References 223 publications

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“…Gene imprinting is an epigenetic process, which allows a subset of genes to be expressed in a monoallelic parent-of-origin manner (Lawrence & Moley 2008). Imprinting occurs in genes that have been shown to be essential for embryonic growth and development, placental function and postnatal behaviour (Isles & Holland 2005, Fowden et al 2006, Smith et al 2006. The main epigenetic mechanisms controlling imprinting are DNA methylation and histone modification.…”

Section: Ovarian Stimulation and Epigeneticsmentioning

confidence: 99%

The impact of ovarian stimulation for IVF on the developing embryo

Santos¹,

Kuijk²,

Macklon³

2010

Reproduction

174

128

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The use of assisted reproductive technologies (ART) has been increasing over the past three decades, and, in developed countries, ART account for 1-3% of annual births. In an attempt to compensate for inefficiencies in IVF procedures, patients undergo ovarian stimulation using high doses of exogenous gonadotrophins to allow retrieval of multiple oocytes in a single cycle. Although ovarian stimulation has an important role in ART, it may also have detrimental effects on oogenesis, embryo quality, endometrial receptivity and perinatal outcomes. In this review, we consider the evidence for these effects and address possible underlying mechanisms. We conclude that such mechanisms are still poorly understood, and further knowledge is needed in order to increase the safety of ovarian stimulation and to reduce potential effects on embryo development and implantation, which will ultimately be translated into increased pregnancy rates and healthy offspring.

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Section: Ovarian Stimulation and Epigeneticsmentioning

confidence: 99%

The impact of ovarian stimulation for IVF on the developing embryo

Santos¹,

Kuijk²,

Macklon³

2010

Reproduction

174

128

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“…Briefly, many imprinted genes have roles in the regulation of foetal and/or placental growth and development. Others play key roles in neurological pathways and in behaviour (Smith et al 2006, Wilkinson et al 2007. As a consequence, perturbations in imprinted gene expression are an important cause of several growth and behavioural syndromes in humans including the Silver-Russell, Beckwith-Wiedemann, Prader-Willi and Angelman syndromes (Hirasawa & Feil 2010).…”

Section: Introductionmentioning

confidence: 99%

Genomic imprinting in germ cells: imprints are under control

Arnaud¹

2010

Reproduction

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The cis-acting regulatory sequences of imprinted gene loci, called imprinting control regions (ICRs), acquire specific imprint marks in germ cells, including DNA methylation. These epigenetic imprints ensure that imprinted genes are expressed exclusively from either the paternal or the maternal allele in offspring. The last few years have witnessed a rapid increase in studies on how and when ICRs become marked by and subsequently maintain such epigenetic modifications. These novel findings are summarised in this review, which focuses on the germline acquisition of DNA methylation imprints and particularly on the combined role of primary sequence specificity, chromatin configuration, non-histone proteins and transcriptional events.

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“…IGF2 is a key factor in human growth and development and is maternally imprinted (9). Imprinting is maintained through the IGF2 differentially methylated region (DMR), the hypomethylation of which leads to bi-allelic expression of IGF2 (10).…”

mentioning

confidence: 99%

Persistent epigenetic differences associated with prenatal exposure to famine in humans

Heijmans

Tobi²,

Stein³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

2,709

1,924

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Extensive epidemiologic studies have suggested that adult disease risk is associated with adverse environmental conditions early in development. Although the mechanisms behind these relationships are unclear, an involvement of epigenetic dysregulation has been hypothesized. Here we show that individuals who were prenatally exposed to famine during the Dutch Hunger Winter in 1944 -45 had, 6 decades later, less DNA methylation of the imprinted IGF2 gene compared with their unexposed, same-sex siblings. The association was specific for periconceptional exposure, reinforcing that very early mammalian development is a crucial period for establishing and maintaining epigenetic marks. These data are the first to contribute empirical support for the hypothesis that early-life environmental conditions can cause epigenetic changes in humans that persist throughout life.developmental origins ͉ DNA methylation ͉ insulin-like growth factor II ͉ nutrition ͉ periconception S uperimposed on the DNA sequence is a layer of epigenetic information that is heritable, particularly during mitosis, and controls the potential of a genomic region to be transcribed (1). Methyl groups coupled to cytosines in cytosine-guanine (CpG) dinucleotides and modifications of histones that package the DNA are the two main molecular marks that compose this information and regulate chromatin structure and DNA accessibility (2).Animal studies have indicated that certain transient environmental influences can produce persistent changes in epigenetic marks that have life-long phenotypic consequences (3, 4). Early embryonic development is of special interest in this respect, because this is a crucial period for establishing and maintaining epigenetic marks (5). Indeed, culturing of preimplantation mice embryos found that epigenetic marks are susceptible to nutritional conditions in the very early stages of mammalian development (6, 7). One of the rare opportunities for studying the relevance of such findings to humans is presented by individuals who were prenatally exposed to famine during the Dutch Hunger Winter (8). This period of famine was the consequence of a Germanimposed food embargo in the western part of The Netherlands toward the end of World War II in the winter of 1944-45. During this period, registries and health care remained intact, so that individuals who were prenatally exposed to this famine can be traced. Moreover, the period of famine was clearly defined, and official food rations were documented. These unique features allow us to assess whether prenatal exposure to famine is associated with persistent epigenetic differences in humans.One of the best-characterized epigenetically regulated loci is insulin-like growth factor II (IGF2). IGF2 is a key factor in human growth and development and is maternally imprinted (9). Imprinting is maintained through the IGF2 differentially methylated region (DMR), the hypomethylation of which leads to bi-allelic expression of IGF2 (10). We recently studied IGF2 DMR methylation in 372 twins (11). IGF2 D...

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Regulation of growth and metabolism by imprinted genes

Cited by 175 publications

References 223 publications

The impact of ovarian stimulation for IVF on the developing embryo

The impact of ovarian stimulation for IVF on the developing embryo

Genomic imprinting in germ cells: imprints are under control

Persistent epigenetic differences associated with prenatal exposure to famine in humans

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