Improvement of gamete quality by stimulating and feeding the endogenous antioxidant system: mechanisms, clinical results, insights on gene-environment interactions and the role of diet

Abstract

Oxidative damage triggers extensive repair in gametes and thereafter in the zygote but it results in clinically relevant damage when affecting the maturation of the gametes chromatin, i.e. padlocking and epigenetic marking. It associates with defective DNA methylation and/or with oxidation of the methyl marks leading to derangement of gamete epigenetics, defects of chromatin condensation and aneuploidy. A proper feed to the one carbon cycle has the potential to stimulate the endogenous antioxidant defences, i.e. gluthatione synthesis, and to activate compensative homeostatic mechanisms restoring both the oxy-redox balance and DNA methylation, which are indeed strictly cross-regulated. This has been shown to produce measurable clinical improvements of male reproductive potential in pilot studies herein summarised. However, the effects of dietary habits and of supplementations are variable according to the individual genetic substrate, as genetic variants of several of the concerned enzymes occur with high frequency. Individual risk assessments and personalised interventions are still difficult to implement, in the meantime, a very varied diet may facilitate metabolic compensation in the majority of the cases. This review aims to report on the mechanisms of damage, on the opportunities to modulate the physiologic oxy-redox homeostasis by means of a varied diet or dietary supplements and on the open issues related to the genetic variability of the population.

One‐carbon cycle support rescues sperm damage in experimentally induced varicocoele in rats

“…These effects can be attributed to the complex composition of Condensyl that contains a mix of group B vitamins together with quercetin, betalains, vitamin E, N-acetylcysteine, and zinc. It is worthy to note that these substances are well represented within a Mediterranean type diet [16], further endorsing the role of a healthy diet in support of reproductive competence.…”

Micronutrients in support to the one carbon cycle for the modulation of blood fasting homocysteine in PCOS women

“…Excess of circulating Hcy is removed by three alternative pathways: Hcy re-methylation to methionine by a methyl group donated by either methyl-tetrahydrofolate or betaine and Hcy transsulfuration to cysteine, which can be then used for the synthesis of the universal cellular antioxidant glutathione [14]. Imbalances of any of the above pathways result in accumulation of Hcy and it is very difficult to understand which of the pathways is responsible for HHcy in the single case.…”

Epigenetics and oxidative stress: A twin‐edged sword in spermatogenesis

“…Thymine formation is also very important that takes place by the deamination of the 5‐MeC, 8‐oxoG or 5‐MeC to 5HmC since it inhibits the binding of the methyl CpG‐binding domain proteins to corresponding CpGs. Binding of the DNA for DNMT3A will be weakened, resulting in poor methylation (Dattilo, Giuseppe, Ettore, & Ménézo, ). Therefore, oxidative damage to DNA might result in the heritable epigenetic changes through the modifications to the chromatin organisation (Donkena, Young, & Tindall, ).…”