Epigenetic alterations in sperm associated with male infertility

Kitamura, Akane; Miyauchi, Naoko; Hamada, Hirofumi; Hiura, Hitoshi; Chiba, Hayato; Okae, Hiroaki; Satô, Akiko; Roshan, John; Arima, Takahiro

doi:10.1111/cga.12113

Cited by 54 publications

(33 citation statements)

References 132 publications

(219 reference statements)

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“…Several studies have demonstrated that an alteration in the sperm epigenome negatively affects fertility and the future embryo [Castillo et al 2015;Hammoud et al 2010;Kitamura et al 2015]. Therefore, sperm epigenetic evaluation seems necessary before ICSI.…”

Section: Discussionmentioning

confidence: 99%

Pronuclear epigenetic modification of protamine deficient human sperm following injection into mouse oocytes

Rajabi

Mohseni-Kouchesfehani

Mohammadi‐Sangcheshmeh

et al. 2016

Systems Biology in Reproductive Medicine

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Epigenetic abnormalities and abnormal chromatin structure in sperm may lead to male infertility. Protamine deficiency is among the disorders of chromatin structure in sperm. The study of epigenetic changes in male pronuclei is necessary since abnormal sperm is sometimes used to create embryos using assisted reproductive techniques. The present study was carried out to compare epigenetic global marks in male pronuclei derived from normal and protamine deficient sperm cells. To do so, interspecies fertilization was used to obtain the male pronucleus. Normal and protamine deficient sperm cells, which were identified by chromomycin A3 staining, were injected into mouse oocytes. Oocytes were cultured until pronuclear formation and were then labeled with different antibodies (anti 5-methylcytosine, anti 5-hydroxymethylcytosine, and anti acetyl H4K12). Based on the fluorescence intensity, the level of each of these epigenetic factors was determined and they revealed a significant relationship between the level of sperm protamine deficiency and sperm epigenetic factors. Protamine deficiency was found to be associated with an increased methylation (p=0) and decreased hydroxymethylation rate (p=0.015) of the male pronucleus chromatin. However, no association was found between protamine deficiency and the level of H4K12 acetylation (p=0.548). Also, the efficiency of fertilization in protamine deficient sperm cells was less than normal. These results suggest that protamine deficient sperm cells lead to the formation of epigenetically altered pronuclei.

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Section: Discussionmentioning

confidence: 99%

Pronuclear epigenetic modification of protamine deficient human sperm following injection into mouse oocytes

Rajabi

Mohseni-Kouchesfehani

Mohammadi‐Sangcheshmeh

et al. 2016

Systems Biology in Reproductive Medicine

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“…Alterations in DNA methylation-mediated genomic imprinting have been observed more frequently in men with oligoasthenoteratozoospermia and oligozoospermia (115). However, whether methylation defects in imprinted genes will affect the development and growth processes of ART offspring remains to be elucidated.…”

Section: Dna Methylation and Male Infertilitymentioning

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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“…If both the establishment and maintenance of epigenetic machinery are costly, then environmental conditions both during development and during adult life may be expected to affect the epigenome. Such costs may be expected to apply to the maintenance of the epigenome in the soma as well as the germ-line, where epigenetic changes resulting from environmental perturbations can be transmitted to offspring (Lambrot et al 2013;Guerrero-Bosagna and Skinner 2014;Kitamura et al 2015). This could explain why both juvenile and adult environments are sometimes found to influence paternal effects on offspring fitness (Ducatez et al 2012; Adler and Bonduriansky 2013; Braun and Champagne 2014; Fricke et al 2015;Macartney et al 2017).…”

Section: Is Epigenetic Machinery Costly To Build and Maintain?mentioning

confidence: 99%

Epigenetic paternal effects as costly, condition-dependent traits

2018

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It is now recognized that post-copulatory traits, such as sperm and ejaculate production can impose metabolic costs, and such traits are therefore expected to exhibit condition-dependent expression, whereby, low condition individuals experience a greater marginal cost of investment compared to high condition individuals. Ejaculates are especially costly in species where males invest in offspring quality through nutrient-rich spermatophores or other seminal nuptial gifts. However, recent evidence shows that, in species where males do not provision females or offspring, males can still influence offspring development through paternal effects mediated by epigenetic factors, such as non-coding RNAs, DNA methylation and chromatin structure. Because such epigenetic paternal effects do not involve the transfer of substantial quantities of resources, such as nutrients, the costs of conferring such effects have not been considered. Here we argue that if selection favours paternal investment in offspring quality through epigenetic factors, then the epigenetic machinery required to bring about such effects may also be expected to evolve strongly condition-dependent expression. We outline indirect evidence suggesting that epigenetic paternal effects could impose substantial metabolic costs, consider the conditions under which selection may act on such effects, and suggest ways to test for differential costs and condition-dependence of these effects. Incorporating epigenetic paternal effects into condition-dependent life history theory will further our understanding of the heritability of fitness and the evolution of paternal investment strategies.

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Epigenetic alterations in sperm associated with male infertility

Cited by 54 publications

References 132 publications

Pronuclear epigenetic modification of protamine deficient human sperm following injection into mouse oocytes

Pronuclear epigenetic modification of protamine deficient human sperm following injection into mouse oocytes

DNA methylation in spermatogenesis and male infertility

Epigenetic paternal effects as costly, condition-dependent traits

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