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Oxidative Stress Induced Damage to Paternal Genome and Impact of Meditation and Yoga

August 27, 2018 - oxidativestress

 Can it Reduce Incidence of Childhood Cancer?

Sperm DNA damage is the underlying etiology of poor implantation and pregnancy rates but also affects the health of offspring and may also result in denovo mutations in germline and post-fertilization. This may result in complex diseases, polygenic disorders, and childhood cancers.

Childhood cancer like retinoblastoma (RB) is more prevalent in developing countries and the incidence of RB has increased more than three-fold in India in the last decade. Recent studies have documented an increased incidence of cancers in children born to fathers who consume alcohol in excess and tobacco or who were conceived by assisted conception. The etiology of childhood cancer and increased disease burden in these children is linked to oxidative stress (OS) and oxidative DNA damage( ODD) in sperm of their fathers. Though several antioxidants are in use to combat oxidative stress, the effect of the majority of these formulations on DNA is not known. Yoga and meditation cause a significant decline in OS and ODD and aid in regulating OS levels such that reactive oxygen speues meditated signal transduction, gene expression, and several other physiological functions are not disrupted. Thus, this study aimed to analyze sperm ODD as a possible etiological factor in childhood cancer and role of simple lifestyle interventions like yoga and meditation in significantly decreasing seminal oxidative stress and oxidative DNA damage and thereby decreasing incidence of childhood cancers.

Materials & Methods: A total of 131 fathers of children with RB (non-familial sporadic heritable) and 50 controls (fathers of healthy children) were recruited at a tertiary center in India. Sperm parameters as per WHO 2010 guidelines and reactive oxygen species (ROS), DNA fragmentation index (DFI), 8-hydroxy-2’-deoxy guanosine (8-OHdG) and telomere length were estimated at day 0, and after 3 and 6 months of intervention. We also examined the compliance with yoga and meditation practice and smoking status at each follow-up. Results: The seminal mean ROS levels (p<0.05), sperm DFI (p<0.001), 8-OHdG (p<0.01) levels were significantly higher in fathers of children with RB, as compared to controls and the relative mean telomere length in the sperm was shorter. Levels of ROS were significantly reduced in tobacco users (p<0.05) as well as in alcoholics (p<0.05) after the intervention. DFI reduced significantly (p<0.05) after 6 months of yoga and meditation practice in all groups. The levels of oxidative DNA damage marker 8-OHdG were reduced significantly after 3 months (p<0.05) and 6 months (p<0.05) of practice.

Conclusions: Our results suggest that OS and ODD DNA may contribute to the development of childhood cancer. This may be due to the accumulation of oxidized mutagenic base 8OHdG, and elevated MDA levels which results in MDA dimers which are also mutagenic, aberrant methylation pattern, altered gene expression which affects cell proliferation and survival through activation of transcription factors. Increased mt DNA mutations and aberrant repair of mt and nuclear DNA due to highly truncated DNA repair mechanisms all contribute to sperm genome hypermutability and persistent oxidative DNA damage. Oxidative stress is also associated with genome-wide hypomethylation, telomere shortening and mitochondrial dysfunction leading to genome hypermutability and instability.

To the best of our knowledge, this is the first study to report a decline in OS and ODD and improvement in sperm DNA integrity following adoption of meditation and yoga-based lifestyle modification. This may reduce disease burden in the next generation and reduce the incidence of childhood cancers.

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