Epigenetic mechanisms involved in developmental nutritional programming

Gabory, Anne; Attig, Linda; Junien, Claudine

doi:10.4239/wjd.v2.i10.164

Cited by 56 publications

(45 citation statements)

References 132 publications

(64 reference statements)

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“…In men with oligoasthenoteratozoospermia, methylation was markedly reduced at all CpGs, reaching statistical significance in subgroups with a sperm concentration of <10x10 6 /ml. These findings suggest that abnormal DNA methylation-mediated genomic imprinting is associated with oligoasthenoteratozoospermia and oligozoospermia (100)(101)(102)(103)(104)(105)(106)(107).…”

Section: Dna Methylation and Male Infertilitymentioning

confidence: 85%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Infertility is a significant problem for human reproduction, with males and females equally affected. However, the molecular mechanisms underlying male infertility remain unclear. Spermatogenesis is a highly complex process involving mitotic cell division, meiosis cell division and spermiogenesis; during this period, unique and extensive chromatin and epigenetic modifications occur to bring about specific epigenetic profiles in spermatozoa. It has recently been suggested that the dysregulation of epigenetic modifications, in particular the methylation of sperm genomic DNA, may serve an important role in the development of numerous diseases. The present study is a comprehensive review on the topic of male infertility, aiming to elucidate the association between sperm genomic DNA methylation and poor semen quality in male infertility. In addition, the current status of the genetic and epigenetic determinants of spermatogenesis in humans is discussed. Contents1. Introduction 2. DNA methylation 3. DNA methylation and spermatogenesis 4. DNA methylation and genomic imprinting 5. DNA methylation and male infertility 6. Conclusion IntroductionEpigenetics is the study of genomic structural modifications that affect gene expression without altering the underlying nucleotide sequence (1-3). Epigenetic mechanisms involved in the regulation of gene expression include the regulation of non-coding RNA, chromatin remodeling, DNA methylation and histone modifications (4,5). Of these mechanisms, DNA methylation has been implicated in numerous biological functions, such as the development of spermatozoa and early embryos, and the repression of endogenous retrotransposons, while it also has a wide range of effects in gene expression (2,3,6). The dysregulation of DNA methylation has previously been associated with various human disorders, and has been shown to increase the risk of fertilization failure, dysfunction in embryogenesis, perinatal mortality, congenital abnormalities, preterm birth and low birth weight (7-11). The present review assesses the significance of DNA methylation in spermatogenesis in order to elucidate the association between the dysregulation of DNA methylation and male infertility. This may provide a basis for the prevention and treatment of male infertility, as well as permit the evaluation of the epigenetic quality of sperm in order to reduce the risk of epigenetic diseases in cases where conception is performed by assisted reproductive technology (ART). DNA methylationEpigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12-14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides. The methylation of constitutive heterochromatic and promoter regions is generally associated with reduced gene transcription (Fig. 1A) (15-18). Therefore, DNA methylation is a type of epigenetic modification that can effectively promote gene silencing (Fig. 1B). The methyl group for this chemical modif...

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Section: Dna Methylation and Male Infertilitymentioning

confidence: 85%

DNA methylation in spermatogenesis and male infertility

Cui¹,

Xuan

Wu³

et al. 2016

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

show abstract

“…reduced number of motor neurons in the earliest-forming motor nuclei involved in the control of swallowing. The influence of prenatal VPA exposure on the developmental programming of the metabolic status of the offspring should not be excluded [43]. Moreover, changes in maternal behavior and/or milk production could indirectly contribute to the poor BW gain in offspring, which remains to be examined in detail [17].…”

Section: Discussionmentioning

confidence: 99%

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development

Podgorac

Pešić

Pavković

et al. 2016

Behavioural Brain Research

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“…Also, it is possible that methylation crosstalk with other epigenetic modifications such as histone marks in the liver and/or other tissues is important in our model. Given the large number of epigenetic modifiers and marks, we still know very little about the ways in which environmental cues may alter chromatin landscapes and regulatory factors to induce global chromatin modifications and control the expression of individual genes [91].…”

Section: Lingonberry Supplementation Alters Genome-wide Dna Methylatimentioning

confidence: 99%

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Heyman-Lindén

Seki

Storm

et al. 2016

The Journal of Nutritional Biochemistry

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The liver is a critical organ for regulation of energy homeostasis and fatty liver disease is closely associated with obesity and insulin resistance. We have previously found that lingonberries, blackcurrants and bilberries prevent, whereas açai berries exacerbate, the development of hepatic steatosis and obesity in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we investigated the mechanisms behind these effects. Genome-wide hepatic gene expression profiling indicates that the protective effects of lingonberries and bilberries are accounted for by several-fold downregulation of genes involved in acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, açai-fed mice exhibit marked upregulation of genes associated with steatosis (e.g. Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with the exacerbation of HF-induced hepatic steatosis in these mice. In silico transcription factor analysis together with immunoblot analysis identified NF-κB, STAT3 and mTOR as upstream regulators involved in mediating the observed transcriptional effects. To gain further insight into mechanisms involved in the gene expression changes, the HELP-tagging assay was used to identify differentially methylated CpG sites. Compared to the HF control group, lingonberries induced genome-wide hypermethylation and specific hypermethylation of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of pathways of metabolic homeostasis and inflammation. We conclude that the beneficial metabolic effects of lingonberries and bilberries are associated with downregulation of inflammatory pathways, whereas for blackcurrants, exerting similar metabolic effects, different mechanisms of action appear to dominate. NF-κB, STAT3 and mTOR are potential targets of the health-promoting effects of berries.

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Epigenetic mechanisms involved in developmental nutritional programming

Cited by 56 publications

References 132 publications

DNA methylation in spermatogenesis and male infertility

DNA methylation in spermatogenesis and male infertility

Early physical and motor development of mouse offspring exposed to valproic acid throughout intrauterine development

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

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