title: Oxidative stress and alterations in DNA methylation: two sides of the same coin in reproduction.
abstract: The negative effect of oxidative stress on the human reproductive process is no longer a matter for debate. Oxidative stress affects female and male gametes and the developmental capacity of embryos. Its effect can continue through late stages of pregnancy. Metabolic disorders and psychiatric problems can also be caued by DNA methylation and epigenetic errors. Age has a negative effect on oxidative stress and DNA methylation, and recent observations suggest that older men are at risk of transmitting epigenetic disorders to their offspring. Environmental endocrine disruptors can also increase oxidative stress and methylation errors. Oxidative stress and DNA methylation feature a common denominator: the one carbon cycle. This important metabolic pathway stimulates glutathione synthesis and recycles homocysteine, a molecule that interferes with the process of methylation. Glutathione plays a pivotal role during oocyte activation, protecting against reactive oxygen species. Assisted reproductive techniques may exacerbate defects in methylation and epigenesis. Antioxidant supplements are proposed to reduce the risk of potentially harmful effects, but their use has failed to prevent problems and may sometimes be detrimental. New concepts reveal a significant correlation between oxidative stress, methylation processes and epigenesis, and have led to changes in media composition with positive preliminary clinical consequences.
authors.affiliation: London Fertility Associates, Harley St, London, UK; Laboratoire Clement, Avenue d'Eylau, Paris, France. Electronic address: yves.menezo@gmail.com.
authors.forename: Yves J R
authors.initials: YJ
authors.lastname: Menezo
authors.affiliation: Clinique Natecia, Lyon, France.
authors.forename: Erica
authors.initials: E
authors.lastname: Silvestris
authors.affiliation: Centre for Assisted Fertilization, Naples, Italy.
authors.forename: Brian
authors.initials: B
authors.lastname: Dale
authors.affiliation: Bourn Hall Clinic, Cambridge, UK.
authors.forename: Kay
authors.initials: K
authors.lastname: Elder
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D001755:Blastocyst; D019175:DNA Methylation; D004715:Endometriosis / Q000503:physiopathology; D044127:Epigenesis, Genetic; D005260:Female; D005298:Fertility; D005609:Free Radicals / Q000737:chemistry; D006801:Humans; D007248:Infertility, Male / Q000503:physiopathology; D008297:Male; D008659:Metabolic Diseases / Q000503:physiopathology; D051379:Mice; D009865:Oocytes / Q000166:cytology / Q000378:metabolism; D010053:Ovary / Q000378:metabolism; D018384:Oxidative Stress; D011085:Polycystic Ovary Syndrome / Q000503:physiopathology; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D012098:Reproduction / Q000502:physiology*; D027724:Reproductive Techniques, Assisted; D012306:Risk; D013094:Spermatozoa / Q000378:metabolism
chemical_list: D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species
keywords: 1-C cycle; endocrine disruptors; homocysteine; imprinting; methylation; oxidative stress