Congenital hydrocephalus : new Mendelian mutations and evidence for oligogenic inheritance

Peer reviewe

Antioxidants modulation of sperm genome and epigenome damage: Fact or fad? Converging evidence from animal and human studies

Increasing evidence suggests that oxidative stress plays a major role in the pathogenesis of sperm DNA damage. Oxidative stress was also recently found to modulate the epigenetic make up of sperm. Along these lines, a growing body of evidence in both experimental and clinical studies has implicated several regimens of antioxidants, by oral administration or in vitro supplementation to sperm-preparation media, in improving various sperm parameters namely DNA damage. While these studies exhibited heterogeneity in treatment regimens, and variability in methodology, there remains a lack of quality evidence on the association between micronutrients and sperm DNA integrity. Another ancillary effect of antioxidants administration on sperm is the shaping of the epigenome. It is beginning to surface that micronutrients function as potent modulators of the sperm epigenome-regulated gene expression through regulation of mainly DNA methylation in humans and experimental models. However, the few promising experimental studies on mice supported the notion that epigenetic marks in spermatogenesis are dynamic and can be modulated by nutritional exposure. More so, the sperm epigenome was proposed to transfer a so-called epigenomic map to the offspring which can influence their development. Here, we review and summarize the current evidence in human and animal models research regarding the link between genome and epigenome × micronutrients environment interactions on the sperm nuclear damage. Unfortunately, our conclusion is not very conclusive, rather, it opens an avenue to investigate the fortifying effect of antioxidants on sperm cells. Hopefully, further genome and epigenome-wide studies focusing on the prenatal environment, will serve as a promising route for embodying the possibility of “normalization” and restoration of some offspring health cues. Keywords: Sperm, Antioxidants, Micronutrients, Reactive oxygen species, Genome, Epigenom

High level of DNA

Assessment of male fertility has been based on routine semen analysis established by the World Health Organization (WHO), evaluating sperm concentration, motility and morphology. Actually, these parameters become less reliable markers to evaluate male fertility potential. Therefore, a search for better markers has led to an increased focus on sperm chromatin integrity testing in fertility work-up and assisted reproductive technologies (ART). In this study, we evaluate sperm DNA fragmentation in 185 Lebanese infertile patients attending fertility clinics all over the country, in comparison with 30 control men of proven fertility, using the sperm chromatin dispersion test (SCD). Our results showed a significantly higher sperm DNA fragmentation in infertile group compared to control group (20.62% vs 12.96%; p < 0.001). In addition, we found that sperm DNA fragmentation is correlated with alterations in sperm parameters: count, motility and morphology. Moreover, we showed that 28% of normozoospermic patients have high sperm DNA fragmentation. Also, a positive correlation was found between sperm DNA fragmentation and ART failure in infertile group patients. Finally, sperm DNA fragmentation is suggested to be associated with tobacco and environmental conditions