DNA methylation and adiposity phenotypes: an epigenome-wide association study among adults in the Strong Heart Study.

BACKGROUND: Elevated adiposity is often posited by medical and public health researchers to be a risk factor associated with cardiovascular disease, diabetes, and other diseases. These health challenges are now thought to be reflected in epigenetic modifications to DNA molecules, such as DNA methylation, which can alter gene expression. METHODS: Here we report the results of three Epigenome Wide Association Studies (EWAS) in which we assessed the differential methylation of DNA (obtained from peripheral blood) associated with three adiposity phenotypes (BMI, waist circumference, and impedance-measured percent body fat) among American Indian adult participants in the Strong Heart Study. RESULTS: We found differential methylation at 8264 CpG sites associated with at least one of our three response variables. Of the three adiposity proxies we measured, waist circumference had the highest number of associated differentially methylated CpGs, while percent body fat was associated with the lowest. Because both waist circumference and percent body fat relate to physiology, we focused interpretations on these variables. We found a low degree of overlap between these two variables in our gene ontology enrichment and Differentially Methylated Region analyses, supporting that waist circumference and percent body fat measurements represent biologically distinct concepts. CONCLUSIONS: We interpret these general findings to indicate that highly significant regions of the genome (DMR) and synthesis pathways (GO) in waist circumference analyses are more likely to be associated with the presence of visceral/abdominal fat than more general measures of adiposity. Our findings confirmed numerous CpG sites previously found to be differentially methylated in association with adiposity phenotypes, while we also found new differentially methylated CpG sites and regions not previously identified.

Impact of Group vs Individual Embryo Culture Strategies on Blastocyst and Clinical Outcomes.

Embryo culture is one of the most important steps in an assisted reproduction laboratory. Embryos can be cultured individually, one embryo per media drop, or in groups, culturing several embryos in the same media drop. Due to the controversy generated on this subject, we wondered which embryo culture method would have the best results in terms of quality and blastocyst formation rate. We designed a prospective randomized study comparing two different embryo culture strategies: group and individual embryo culture. The data were obtained from 830 embryos from 103 egg donation treatments. The zygotes were randomized into two groups: individual culture (group 1) or group culture (group 2). The embryos were cultured in 35-µl drops until day 5 when they were classified morphologically. We observed a significant increase in the blastocyst formation rate and in the usable embryo rate in individual culture on day 5 compared to group culture. However, good embryo quality (A/B blastocysts), implantation, and pregnancy rates were similar regardless of the type of embryo-culture. As a conclusion, individual culture may increase blastocyst formation rate and may benefit embryo quality on day 5. Our results support previous reports suggesting that individual culture could improve embryo development.