Epigenetic regulation in heart failure

Kim, Soo Young; Morales, Cyndi R.; Gillette, Thomas G.; Hill, Joseph A.

doi:10.1097/hco.0000000000000276

Cited by 42 publications

(35 citation statements)

References 157 publications

(141 reference statements)

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“…During spermatogenesis, epigenetic mechanisms acts as critical regulators for gene expression, which in turn have control on male reproductive function [109][110][111]. In male reproductive function, epigenetic regulation plays a major role by controlling germ cell growth and maintenance [111][112][113][114][115]. DNA methylation is a kind of epigenetic alteration that can efficiently endorse gene silencing.…”

Section: Impact Of Epigenetic Regulation In Spermatogenesis and Male mentioning

confidence: 99%

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

Laleethambika

Venugopal

Chandran

et al. 2018

SN Compr. Clin. Med.

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Diabetes mellitus (DM) represents one of the major threats to human health all over the world, affecting almost every system of the body. Its prevalence is escalating globally and is associated with reproductive impairment in both males and females. Reports on male infertility due to DM is lacking since most affected individuals are unaware of their infertility condition due to the late onset of DM. Glucose metabolism is an imperative occasion in spermatogenesis, causing adverse effects on male fertility, principally on sperm DNA quality, motility, and ingredients of seminal plasma. DM is coupled with an increased oxidative stress (OS), causing sperm nuclear and mitochondrial DNA damage. Reactive oxygen species (ROS) hassles the fluidity of sperm plasma membrane, decreases sperm motility and ability to fuse with oocyte as well as altering the sperm DNA integrity. Lamentably, spermatozoa cannot repair the damage initiated by excessive ROS as they do not have the cytoplasmic enzymes required to achieve the repair. Diabetes may impact the epigenetic change during spermatogenesis which may be inherited through male gamete to more than one generation increasing the risk of diabetes in offspring. Administration of antioxidants in male infertility has started to pull in significant intrigue. Many studies have shown that antioxidants amazingly reduce the oxidative stress markers and boost the antioxidant enzymes. Currently treatment strategies are aimed at lowering ROS levels to maintain normal cell function. This review highlights the potential impact of DM on sperm DNA integrity, epigenetic dysregulation and efficacy of antioxidant therapy.

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Section: Impact Of Epigenetic Regulation In Spermatogenesis and Male mentioning

confidence: 99%

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

Laleethambika

Venugopal

Chandran

et al. 2018

SN Compr. Clin. Med.

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“…Epigenetic mechanisms are critical regulators of gene expression during spermatogenesis that may influence male fertility (12)(13)(14). Cytosine, a key DNA base, is methylated at the position, typically in the context of CpG dinucleotides.…”

Section: Dna Methylationmentioning

confidence: 99%

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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“…Epigenetic mechanisms, including DNA methylation, have been proposed to underlie pathologic remodeling of the failing heart (28, 29). To determine whether CRS alters DNA methylation patterns in the heart, we used RRBS to analyze the genome‐wide methylation profiles of cardiac tissues from CRS and NS mice.…”

Section: Resultsmentioning

confidence: 99%

Contribution of DNA methylation in chronic stress‐induced cardiac remodeling and arrhythmias in mice

Zhang¹,

Li²,

Liu³

et al. 2019

The FASEB Journal

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It is recognized that stress can induce cardiac dysfunction, but the underlying mechanisms are not well understood. The present study aimed to test the hypothesis that chronic negative stress leads to alterations in DNA methylation of certain cardiac genes, which in turn contribute to pathologic remodeling of the heart. We found that mice that were exposed to chronic restraint stress (CRS) for 4 wk exhibited cardiac remodeling toward heart failure, as characterized by ventricular chamber dilatation, wall thinning, and decreased contractility. CRS also induced cardiac arrhythmias, including intermittent sinus tachycardia and bradycardia, frequent premature ventricular contraction, and sporadic atrioventricular conduction block. Circulating levels of stress hormones were elevated, and the cardiac expression of tyrosine hydroxylase, a marker of sympathetic innervation, was increased in CRS mice. Using reduced representation bisulfite sequencing, we found that although CRS did not lead to global changes in DNA methylation in the murine heart, it nevertheless altered methylation at specific genes that are associated with the dilated cardiomyopathy (DCM) (e.g., desmin) and adrenergic signaling of cardiomyocytes (ASPC) (e.g., adrenergic receptor‐α1) pathways. We conclude that CRS induces cardiac remodeling and arrhythmias, potentially through altered methylation of myocardial genes associated with the DCM and ASPC pathways.—Zhang P., Li, T., Liu, Y.‐Q., Zhang, H., Xue, S.‐M., Li, G., Cheng, H.‐Y.M., Cao, J.‐M. Contribution of DNA methylation in chronic stress‐induced cardiac remodeling and arrhythmias in mice. FASEB J. 33, 12240‐12252 (2019). http://www.fasebj.org

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Epigenetic regulation in heart failure

Cited by 42 publications

References 157 publications

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

Diabetes and Sperm DNA Damage: Efficacy of Antioxidants

DNA methylation in spermatogenesis and male infertility

Contribution of DNA methylation in chronic stress‐induced cardiac remodeling and arrhythmias in mice

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