Epigenetic modifications and reprogramming in paternal pronucleus: sperm, preimplantation embryo, and beyond

Okada, Yuki; Yamaguchi, Kosuke

doi:10.1007/s00018-016-2447-z

Cited by 46 publications

(26 citation statements)

References 101 publications

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“…The advantage of epigenetic alterations over genetic mutations is their potential reversibility [ 144 ]. Based on this property, a number of recent experimental studies aimed to demonstrate the reversibility of newly environmental-induced epigenetic modifications.…”

Section: Paternal Obesity and Consequence On The Metabolic Health Promentioning

confidence: 99%

Paternal obesity: how bad is it for sperm quality and progeny health?

Raad

Hazzouri

Bottini

et al. 2017

Basic Clin. Androl.

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There is substantial evidence that paternal obesity is associated not only with an increased incidence of infertility, but also with an increased risk of metabolic disturbance in adult offspring. Apparently, several mechanisms may contribute to the sperm quality alterations associated with paternal obesity, such as physiological/hormonal alterations, oxidative stress, and epigenetic alterations. Along these lines, modifications of hormonal profiles namely reduced androgen levels and elevated estrogen levels, were found associated with lower sperm concentration and seminal volume. Additionally, oxidative stress in testis may induce an increase of the percentage of sperm with DNA fragmentation. The latter, relate to other peculiarities such as alteration of the embryonic development, increased risk of miscarriage, and development of chronic morbidity in the offspring, including childhood cancers. Undoubtedly, epigenetic alterations (ie, DNA methylation, chromatin modifications, and small RNA deregulation) of sperm related to paternal obesity and their consequences on the progeny are poorly understood determinants of paternal obesity-induced transmission. In this review, we summarize and discuss the data available in the literature regarding the biological, physiological, and molecular consequences of paternal obesity on male fertility potential and ultimately progeny health.

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Section: Paternal Obesity and Consequence On The Metabolic Health Promentioning

confidence: 99%

Paternal obesity: how bad is it for sperm quality and progeny health?

Raad

Hazzouri

Bottini

et al. 2017

Basic Clin. Androl.

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“…The maternally and paternally inherited genomes exhibit asymmetries from the start in the mammalian zygote as a consequence of the differential epigenetic reprogramming during oogenesis and spermatogenesis (2)(3)(4)(5)(6)(7)(8). The asymmetry continues after fertilization when the two half genomes are organized separately in the paternal and maternal pronuclei and treated differently by the epigenetic machinery deposited in the oocyte (9). The paternally inherited chromosomes that arrive from the sperm are packaged in protamines, replaced by transitory histones after fertilization, and then finally replaced by canonical histones after replication of the DNA.…”

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confidence: 99%

EHMT2 and SETDB1 protect the maternal pronucleus from 5mC oxidation

Zeng

Han

Pierce

et al. 2019

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

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Genome-wide DNA "demethylation" in the zygote involves global TET3-mediated oxidation of 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in the paternal pronucleus. Asymmetrically enriched histone H3K9 methylation in the maternal pronucleus was suggested to protect the underlying DNA from 5mC conversion. We hypothesized that an H3K9 methyltransferase enzyme, either EHMT2 or SETDB1, must be expressed in the oocyte to specify the asymmetry of 5mC oxidation. To test these possibilities, we genetically deleted the catalytic domain of either EHMT2 or SETDB1 in growing oocytes and achieved significant reduction of global H3K9me2 or H3K9me3 levels, respectively, in the maternal pronucleus. We found that the asymmetry of global 5mC oxidation was significantly reduced in the zygotes that carried maternal mutation of either the Ehmt2 or Setdb1 genes. Whereas the levels of 5hmC, 5fC, and 5caC increased, 5mC levels decreased in the mutant maternal pronuclei. H3K9me3-rich rings around the nucleolar-like bodies retained 5mC in the maternal mutant zygotes, suggesting that the pericentromeric heterochromatin regions are protected from DNA demethylation independently of EHMT2 and SETDB1. We observed that the maternal pronuclei expanded in size in the mutant zygotes and contained a significantly increased number of nucleolar-like bodies compared with normal zygotes. These findings suggest that oocyte-derived EHMT2 and SETDB1 enzymes have roles in regulating 5mC oxidation and in the structural aspects of zygote development.maternal effect | 5-hydroxymethylcytosine | 5-methylcytosine | EHMT2 | STEDB1

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“…During development the epigenome undergoes extensive modification with epigenetic remodeling driving cellular differentiation to establish cell- and tissue-specific pattern of gene expression. Concurrently, in mammals the germline is undergoing waves of erasure and reestablishment of epigenetic marks to reprogram the epigenome for the next generation (Perino and Veenstra, 2016 ; Iurlaro et al, 2017 ; Okada and Yamaguchi, 2017 ). Epigenetic dysregulation had been proposed as a potential mechanism underlying anomalous fetal programming.…”

Section: Fetal Programmingmentioning

confidence: 99%