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Research Letter |

Link Between Increased Prevalence of Autism Spectrum Disorder Syndromes and Oxidative Stress, DNA Methylation, and Imprinting The Impact of the Environment

Yves J. R. Menezo, PhD, DSc1; Kay Elder, PhD, MD2; Brian Dale, PhD, DSc3
[+] Author Affiliations
1London Fertility Associates, London, England
2Bourn Hall Clinic, Cambridge, England
3Centre for Assisted Fertilization, Naples, Italy
JAMA Pediatr. 2015;169(11):1066-1067. doi:10.1001/jamapediatrics.2015.2125.
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This study examines the biochemical link between the process of DNA methylation in gametes and autism.

Autism is a complex neurodevelopment disorder, with a male to female prevalence of 4.3:1. The number of children diagnosed with autism or related disorders has increased at an alarming rate: the Centers for Disease Control and Prevention estimates that 1 in 68 children in the United States (or 14.7 per 1000 eight-year-olds) was identified with autism spectrum disorder during 2014. The figure reaches 1 in 45 children in the state of Alabama, and this represents an estimated 30% increase over previous estimates reported in 2012. The prevalence of these disorders has more than doubled since 2000. Here we discuss the biochemical link between the process of DNA methylation in gametes and autism.

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Interrelations Between Oxidative Stress and Methylation Processes

1, Correct recycling of homocysteine allows generation of cysteine and methionine, which allow correct processes of methylation through the formation of S-adenosyl methionine (SAM) (1bis). 2, Correct generation of cysteine allows the synthesis of hypotaurine and glutathione, 2 potent inhibitors of reactive oxygen species (ROS). Hypotaurine is the most important anti-ROS naturally present in vivo in the natural environment of the preimplantation embryo. 3, Generation of ROS induces DNA fragmentation. Advanced age decreases the ability to control ROS-linked decays. 4, High levels of homocysteine perturb DNA methylation processes in sperm, oocytes, and embryos. 5, DNA methylation defects, whether or not linked to imprinting, may result in negative transgenerational health problems. Unrepaired 8 oxoG (oxidized form of guanine) leads to aberrant methylation at CpG sites, which impairs transcription and may affect telomere length (TTAGGG repeats). 6, Plastic derived endocrine disruptors (bisphenol A [BPA], di-[2-ethylhexyl]phthalate [DEHP], and dibutyl phthalate [DBP]) have a negative effect on all of the steps in the pathway.

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