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Physical activity is a first-line treatment for polycystic ovary syndrome (PCOS). Resistance or aerobic exercise improves metabolic complications, reproductive outcomes, and quality of life in PCOS. DNA methylation reprogramming during exercise may be the major modifier behind these changes. We sought to evaluate genome-wide DNA methylation changes after supervised resistance and aerobic exercise in women with PCOS. Exercises were performed in 56 women with PCOS (resistance, n  = 30; aerobic, n  = 26), for 16 weeks (wks), three times per week, in 50-minute to one-hour sessions. Anthropometric indices and hormonal and metabolic parameters were measured before and after training. Genome-wide leukocyte DNA methylation was analysed by Infinium Human MethylationEPIC 850K BeadChip microarrays (Illumina). Both resistance and aerobic exercise improved anthropometric indices, metabolic dysfunction, and hyperandrogenism in PCOS after the training programme, but no differences were observed between the two exercises. Resistance and aerobic exercise increased genome-wide DNA methylation, although resistance changed every category in the CpG island context (islands, shores, shelve, and open sea), whereas aerobic exercise altered CpG shores and the open sea. Using a stringent FDR (>40), 6 significantly differentially methylated regions (DMRs) were observed in the resistance exercise cohort and 14 DRMs in the aerobic cohort, all of which were hypermethylated. The increase in genome-wide DNA methylation may be related to the metabolic and hormonal changes observed in PCOS after resistance and aerobic exercise. Since the mammalian genome is hypermethylated globally to prevent genomic instability and ageing, resistance and aerobic exercise may promote health and longevity through environmentally induced epigenetic changes.

Objective: To study the global DNA methylation pattern in spermatozoa of patients with varicocele as well as investigate their semen quality., Design: Prospective observational case-control study., Setting: University-affiliated hospital., Patient(s): A total of 26 men with varicocele and 26 fertile men without the disorder., Interventions: Analysis of semen quality and sperm DNA methylation patterns., Main Outcome Measure(s): Semen quality evaluated by semen analysis, and sperm DNA methylation patterns investigated using the Infinium MethylationEPIC BeadChip platform., Result(s): Men with varicocele displayed decreased semen quality. The sperm DNA methylation analysis showed that men with varicocele exhibit global hypomethylation in comparison with the control group. A total of 59 differentially methylated CpG sites were identified, most of them hypomethylated in the varicocele group. In regional analyses, 1,695 DNA regions were differentially methylated in men with varicocele. These regions show associations with gamete generation, meiotic and meiosis cell cycle, and semen quality based on gene ontology analysis., Conclusion(s): Gene ontology results suggest that changes in methylation may be associated with the low semen quality phenotype observed in some varicocele patients because the observed differentially methylated regions in varicocele patients are related to male reproductive pathways. Additionally, the varicocele grade may influence the magnitude of global sperm DNA methylation change. To our knowledge, this is the first report analyzing changes at a regional or CpG-specific level in men with varicocele., (Copyright © 2020 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the levels of DNA methylation in the KvDMR1 (KvLQT1 differentially methylated region 1) in embryonic and extra-embryonic tissues., Design: Cross-sectional study., Setting: University medical center and clinical hospital., Patient(s): Embryonic and/or extraembryonic tissues (umbilical cord, chorionic villus, chorion, decidua, and/or amnion) collected from 27 first-trimester pregnancies (up to 12 weeks of gestation, single embryos) from elective abortions, extravillous trophoblasts (EVTs) from the top of individual chorionic villi, and chorionic villi from 10 normal full-term placentas collected after birth., Intervention(s): None., Main Outcome Measure(s): DNA methylation of the KvDMR1 region evaluated using quantitative analysis of DNA methylation followed by real-time polymerase chain reaction (qAMP) and bisulfite sequencing (bis-seq) analysis., Result(s): The results showed variability in KvDMR1 DNA methylation in different tissues from the same pregnancy. The average of DNA methylation was not different between the embryo, umbilical cord, amnion, and chorionic villi, despite the relatively low level of methylation observed in the amnion (33.50% ± 14.48%). Chorionic villi from term placentas showed a normal methylation pattern at KvDMR1 (42.60% ± 6.08%). The normal methylation pattern at KvDMR1 in chorionic villi (as well as in EVTs) from first-trimester placentas was confirmed by bis-seq., Conclusion(s): Our results highlight an existing heterogeneity in DNA methylation of the KvDMR1 region during first trimester and a consistent hypomethylation in the amnion in this period of gestation., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Varicocele pathophysiology is related to increased oxidative stress, which might result in loss sperm DNA integrity as well as in genomic instability. Sperm telomere shortening and loss of global DNA methylation are the main features of genomic instability, leading to cell senescence and death, whereas sperm DNA fragmentation (SDF) characterizes the loss of chromatin integrity. We hypothesize that sperm genomic stability and DNA integrity is reduced in infertile men with moderate and large-sized varicoceles, thus being candidate markers of sperm quality in varicocele-related infertility. Here, we assessed the sperm global DNA methylation, telomere length, and SDF in men with and without clinically palpable varicoceles. While the rates of SDF and telomere length were not statistically different between varicocele patients and controls, global sperm DNA methylation seems to be lower in men with varicocele (49.7% ± 20.7%) than controls (64.7% ± 17.1%). A negative correlation between SDF and sperm motility and a positive correlation between sperm morphology and telomere length were observed. Our results suggest that varicocele may result in genomic instability, in particular, global DNA hypomethylation. However, a large sample size may confirm these findings. The understanding of the molecular mechanisms involved in the pathophysiology of varicocele-related infertility may help to better select candidates for varicocele repair.