Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

Stuppia, Liborio; Franzago, Marica; Ballerini, Patrizia; Gatta, Valentina; Antonucci, Ivana

doi:10.1186/s13148-015-0155-4

Cited by 165 publications

(110 citation statements)

References 175 publications

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“…The most common symptom of male infertility is reduced sperm count (oligozoospermia) which is mainly attributed to impaired sperm production (spermatogenesis) (Stuppia et al, 2015). Although the dysfunction of spermatogenesis has been partially explained by genetics, such as deletions and chromosome rearrangements, a large portion of cases remain idiopathic (Krausz et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Louie

Minor

et al. 2016

Andrology

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SUMMARYAltered DNA methylation has been previously identified in the spermatozoa of infertile men; however, the origins of these errors are poorly understood. DNA methylation is an epigenetic modification which is thought to play a fundamental role in male germline development. DNA methylation reactions rely on the cellular availability of methyl donors, which are primarily products of folate metabolism, where a key enzyme is methylenetetrahydrofolate reductase (MTHFR). The MTHFR C677T single nucleotide polymorphism (SNP) reduces enzyme activity and may potentially alter DNA methylation processes during germline development. The objective of this study was to determine whether altered DNA methylation in spermatozoa is associated with the MTHFR C677T SNP. DNA methylation was evaluated at the H19, IG-GTL2, and MEST imprinted differentially methylated regions in the spermatozoa of 53 men -44 oligozoospermic men and nine fertile men with normal sperm parameters via bisulfite sequencing of sperm clones. The 44 infertile men were stratified by severity of oligozoospermia -three normal (>15 million spermatozoa/mL), eight moderate (5-15 million spermatozoa/mL), 23 severe (1-5 million spermatozoa/mL), and 10 very severe (<1 million spermatozoa/mL). MTHFR C677T SNP genotyping was conducted in a subset of 44 peripheral blood samples via restriction fragment length polymorphism. A total of three men -severe oligozoospermic and CT genotype -were found to be altered, which is defined as having ≥50% of their clones altered, where an altered clone was in turn defined as ≥50% of CpGs with incorrect DNA methylation patterns. The incidence of three altered men within the CT subgroup, however, was not significantly higher than the incidence in the CC subgroup. Taken together, altered DNA methylation in spermatozoa was not significantly associated with the MTHFR C677T SNP; however, there was a trend for higher incidence of alterations among severe oligozoospermic infertile men with CT genotypes.

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Section: Introductionmentioning

confidence: 99%

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Louie

Minor

et al. 2016

Andrology

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“…The various epigenetic changes that occur during spermatogenesis depicted in Fig. 4 [39], could be targeted by toxicants with subsequent adverse impact on male fertility.…”

Section: Role Of Epigenetic Mechanisms In Reproductive Toxicitymentioning

confidence: 99%

Oxidative stress in reproductive toxicology

Archibong

Rideout

Harris

et al. 2018

Current Opinion in Toxicology

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Oxidative stress (OS) has been implicated in the causation of environmentally-induced diseases. However, the role of toxicants in the pathophysiology of disorders and diseases affecting the reproductive system are less understood. This review focuses on some of the mechanisms that underlie OS-induced reproductive toxicity at the cellular- and organ levels (germ cell damage and perturbed organ responses to endocrine stimuli). While most of the reproductive and developmental studies conducted in adult animals and transgenerational adult animals point to the involvement of genotoxicity, the part played by epigenetic alterations is accorded a recent recognition, thus warranting more studies in this area. Additionally, metabolomic, proteomic and transcriptomic approaches need to be employed to advance our understanding of key metabolites formed and the expression of anti-OS genes at the molecular level that are necessary for combating reactive oxygen species formation. The resulting data could be analyzed using bioinformatics tools to identify the pathways linked to disease causation and as a consequence, the adoption of therapeutic strategies, including but not limited to administering phytochemicals (many of which possess antioxidant properties) to improve disease outcomes.

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“…In addition, there is a growing concern for epigenetic effects in exposed organisms. For example, altered gene expression and effects on development and physiology after the maternal or even paternal parent is exposed to a chemical, can be observed in the next generation even though the individuals in the next generation are not exposed themselves (Heindel et al, 2006, Nilsson and Skinner, 2015, Perera and Herbstman, 2011, Skinner, 2011, Stuppia et al, 2015, Vandegehuchte and Janssen, 2011. For example, atrazine inhibits meiosis in mice, but also affects gene expression in ways that can be inherited through the germline in the next generation (Gely-Pernot et al, 2015).…”

Section: C Transgenerational Effectsmentioning

confidence: 99%

From silent spring to silent night: Agrochemicals and the anthropocene

Hayes

Hansen

2017

Elementa: Science of the Anthropocene

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Hayes, TB and Hansen, M 2017 From silent spring to silent night: Agrochemicals and the anthropocene. Elem Sci Anth, 5: 57, DOI: https://doi.org/10.1525/elementa.246 IntroductionWe are in the Anthropocene and likely experiencing the Earth's sixth mass extinction. The current mass extinction is the first to be caused by a single species, humans. Chemical contaminants in the environment, especially pesticides, are playing an important role in the Anthropocene. Over 85,000 synthetic chemicals exist today (USEPA, 2014, USEPA, 2016b, NIH, 2014. These chemicals represent compounds used in every aspect of life and can end up in the environment (air, water, soil, and biological tissues). Even personal care products and personal use chemicals (such as pharmaceuticals) can persist in the environment ( Yamamoto et al., 2009, D'Abrosca et al., 2008. Although there are many sources and types of chemicals in the environment, pesticides are a significant concern because they are applied directly in the environment in large amounts, particularly by the agricultural industry. Pesticides are defined by the U.S. Environmental Protection Agency as: "any substance or mixture of substances intended for preventing, destroying, repelling, or mitigating any pest; any substance or mixture of substances intended for use as a plant regulator, defoliant, or desiccant, or any nitrogen stabilizer" (USEPA, 2015c) and include herbicides, fungicides, nematocides, rodenticides, and agents to kill bacteria and viruses. Over the last 75 years, the use of pesticides has increased dramatically and continues to increase. Approximately 2.3 billion kilograms of pesticides are used annually worldwide with the U.S. alone accounting for over 0.45 billion kilograms per year (Alavanja, 2009, USEPA, 2017, USEPA, 2015b. Here, we review evidence that pesticides have altered the gene pool of target organisms and through direct toxic effects and so-called "low dose" effects (effects below concentrations considered safe) have altered landscapes and populations globally REVIEWFrom silent spring to silent night: Agrochemicals and the anthropocene Tyrone B. Hayes * and Martin Hansen *, †We are now living in the Anthropocene, the first time in Earth's history when synthetic chemicalscreated by humans-are damaging the planet and contributing to a major loss of biodiversity. Pesticides are a particular problem in this regard. Agricultural practices changed dramatically following World War II.Methods for the production of nitrogen for manufacturing explosives were adapted for use as fertilizer in agriculture. Further, chemicals used to combat insect vectors for disease during World War II were adapted for the control of insect pests in agriculture. Eventually, herbicides used as defoliants to destroy food supplies and aid in combating soldiers using forests as cover, were customized to control weeds in agriculture. The heavy use of pesticides in agriculture has resulted in global exposure to these chemicals. Travelling through water, air, and in migrating animals, pes...

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Epigenetics and male reproduction: the consequences of paternal lifestyle on fertility, embryo development, and children lifetime health

Cited by 165 publications

References 175 publications

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Evaluation of DNA methylation at imprinted DMRs in the spermatozoa of oligozoospermic men in association withMTHFRC677T genotype

Oxidative stress in reproductive toxicology

From silent spring to silent night: Agrochemicals and the anthropocene

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