Madhuri Tolahunase

Oxidative Stress and Male Infertility

DNA damage, largely owing to oxidative stress, is a leading cause of defective sperm function. High levels of oxidative stress result in damage to sperm DNA, RNA transcripts, and telomeres and, therefore might provide a common underlying aetiology of male infertility and recurrent pregnancy loss, in addition to congenital malformations, complex neuropsychiatric disorders, and childhood cancers in children fathered by men with defective sperm cells. Spermatozoa are highly vulnerable to oxidative stress owing to limited levels of antioxidant defence and a single, limited DNA-damage detection and repair mechanism. Oxidative stress is predominantly caused by a host of lifestyle-related factors, the majority of which are modifiable. Antioxidant regimens and lifestyle modifications could both be plausible therapeutic approaches that enable the burden of oxidative-stress-induced male factor infertility to be overcome. Lifestyle interventions including yoga and meditation can substantially improve the integrity of sperm DNA by reducing levels of oxidative DNA damage, regulating oxidative stress and by increasing the expression of genes responsible for DNA repair, cell-cycle control and anti-inflammatory effects. Oxidative stress is caused by various modifiable factors, and the use of simple interventions can decrease levels of oxidative stress, and therefore reduce the incidence of both infertility and complex diseases in the resultant offspring.

Improvement in Sperm DNA Quality Following Simple Life StyleIntervention: A Study in Fathers of Children with Non-Familial SporadicHeritable Retinoblastoma

Introduction and objectives: Genomic integrity of gametes is important for birth of healthy offspring. As compared to ova the sperm is more susceptible to mutation due to limited DNA damage detection and repair mechanism. Life style habits adopted by father before conception may adversely affect genomic DNA integrity in male gametes. Oxidative stress damages sperm nuclear and mitochondrial DNA. Complementary and alternative medical therapies such as yoga/meditation are being increasingly used as adjuncts to modern medicine in treatment of several clinical conditions. Therefore, in this pilot study, we analyzed the effects of yoga and meditation on seminal oxidative stress and sperm DNA integrity in fathers of children with non-familial sporadic heritable retinoblastoma (Rb) after intervention (3 and 6 months). Methods: A total of 10 men (father of children with sporadic non-familial Rb) were recruited in this study. Semen samples were collected at base line (day 0), 3 months and after 6 months of yoga practice. Reactive oxygen species (ROS), DNA fragmentation index (DFI) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) levels were estimated at day 0.3 months and 6 months interval. Results: There was reduction in mean DFI levels [p>0.05] at 3 months and 6 months [p 0.05] 6 months [p<0.05] with respect to the base line levels (day 0). Conclusions: Yoga/meditation significantly lowers oxidative stress and oxidative nuclear DNA damage, and levels of the mutagenic base 8OHdG. Thus yoga and meditation are simple life style interventions which are therapeutic for maintaining/restoring sperm DNA integrity

Impact of Yoga and Meditation on Cellular Aging in Apparently Healthy Individuals: A Prospective, Open-Label Single-Arm Exploratory Study.

This study was designed to explore the impact of Yoga and Meditation based lifestyle intervention (YMLI) on cellular aging in apparently healthy individuals. During this 12-week prospective, open-label, single arm exploratory study, 96 apparently healthy individuals were enrolled to receive YMLI. The primary endpoints were assessment of the change in levels of cardinal biomarkers of cellular aging in blood from baseline to week 12, which included DNA damage marker 8-hydroxy-2′-deoxyguanosine (8-OH2dG), oxidative stress markers reactive oxygen species (ROS), and total antioxidant capacity (TAC), and telomere attrition markers telomere length and telomerase activity. The secondary endpoints were assessment of metabotrophic blood biomarkers associated with cellular aging, which included cortisol, β-endorphin, IL-6, BDNF, and sirtuin-1. After 12 weeks of YMLI, there were significant improvements in both the cardinal biomarkers of cellular aging and the metabotrophic biomarkers influencing cellular aging compared to baseline values. The mean levels of 8-OH2dG, ROS, cortisol, and IL-6 were significantly lower and mean levels of TAC, telomerase activity, β-endorphin, BDNF, and sirtuin-1 were significantly increased (all values p < 0.05) post-YMLI. The mean level of telomere length was increased but the finding was not significant (p = 0.069). YMLI significantly reduced the rate of cellular aging in apparently healthy population.

Yoga and Meditation as a Therapeutic Intervention in Oxidative Stress and Oxidative DNA Damage to Paternal Genome

Yoga and meditation (encompassing physical postures, breathing practices, relaxation techniques and meditation) is known to modulate neural, endocrine and immune functions at the cellular level through influencing cell cycle control, aging, oxidative stress (OS), apoptosis and several pathways of stress signalling. Individuals with high level of oxidative stress are in great need of safe, inexpensive, non-pharmacologic, accessible, and effective adjunctive therapies to enhance well-being, reduce the burden of such stress and prevent its chronic sequelae. OS is the aetiology in several complex lifestyle diseases (coronary artery disease, hypertension, primary open angle glaucoma, idiopathic male infertility) and autoimmune disorders. Seminal oxidative stress and sperm DNA damage may be the common underlying cause for infertility, recurrent spontaneous abortions, congenital malformations and complex neuropsychiatric disorders in children and in certain childhood cancers. Thus management by antioxidants and simple life style modifications and interventions like meditation and yoga are highly efficacious in management of oxidative stress and its sequelae.

Chapter 9 – Yoga Meditation Lifestyle Intervention: Impact on Male Reproductive Health

Abstract Male infertility, a major lifestyle issue affecting 8%–10% of the adult population, needs to be addressed urgently. Both advances in assisted reproductive technology and a trend to seek it for infertility are increasing at a rapid pace, with enormous psychological and economic consequences for parents and risk of complications for offspring, ranging from neuropsychiatric disorders to cancers. Adoption of yoga in the lifestyle of infertile males has huge potential not only to increase chances of natural pregnancy but also to provide healthy offspring with least complications. Yoga, which has several components such as Asana (postures), Pranayama (breathing exercises), and Dhyana (meditation), benefits male infertility by reversing cellular dysfunctions in male reproductive organs, not only acting directly locally, but also improving disturbances in brain and other systems influencing reproduction. Yoga is known to reverse aging effects and is helpful in infertile adult males, who are affected by both chronological and biological aging, which is increasingly becoming accelerated and pathological because of lifestyle and bioenvironmental factors. Yoga decreases harmful mutations in sperm and contributes to a healthy transgenerational epigenetic memory for the child.Male infertility, a major lifestyle issue affecting 8%–10% of the adult population, needs to be addressed urgently. Both advances in assisted reproductive technology and a trend to seek it for infertility are increasing at a rapid pace, with enormous psychological and economic consequences for parents and risk of complications for offspring, ranging from neuropsychiatric disorders to cancers. Adoption of yoga in the lifestyle of infertile males has huge potential not only to increase chances of natural pregnancy but also to provide healthy offspring with least complications. Yoga, which has several components such as Asana (postures), Pranayama (breathing exercises), and Dhyana (meditation), benefits male infertility by reversing cellular dysfunctions in male reproductive organs, not only acting directly locally, but also improving disturbances in brain and other systems influencing reproduction. Yoga is known to reverse aging effects and is helpful in infertile adult males, who are affected by both chronological and biological aging, which is increasingly becoming accelerated and pathological because of lifestyle and bioenvironmental factors. Yoga decreases harmful mutations in sperm and contributes to a healthy transgenerational epigenetic memory for the child.