Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity.

MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in the regulation of physiological processes, such as adaptation to physical exercise, and also in disease settings, such as systemic arterial hypertension (SAH), type 2 diabetes mellitus (T2D), and obesity. In SAH, microRNAs play a significant role in the regulation of key signaling pathways that lead to the hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, proliferation, and phenotypic change in smooth muscle cells, and the hyperactivation of the sympathetic nervous system. MicroRNAs are also involved in the regulation of insulin signaling and blood glucose levels in T2D, and participate in lipid metabolism, adipogenesis, and adipocyte differentiation in obesity, with specific microRNA signatures involved in the pathogenesis of each disease. Many studies report the benefits promoted by exercise training in cardiovascular diseases by reducing blood pressure, glucose levels, and improving insulin signaling and lipid metabolism. The molecular mechanisms involved, however, remain poorly understood, especially regarding the participation of microRNAs in these processes. This review aimed to highlight microRNAs already known to be associated with SAH, T2D, and obesity, as well as their possible regulation by exercise training.

Erratum to: Familial chromosomal translocation X; 22 associated with infertility and recurrent X mosaicism.

[This corrects the article DOI: 10.1186/s13039-016-0249-5.].

Familial chromosomal translocation X; 22 associated with infertility and recurrent X mosaicism.

BACKGROUND: Individuals with apparently balanced translocations, often, show no clinical findings. However, in meiosis, translocations tend to cause errors on chromosome disjunction and the ones involving sex chromosomes have particular implications for the phenotype. Male carriers of balanced X-autosome translocations are almost invariably infertile due to interruption of the spermatogenesis, but the mechanism is not fully understood. CASE PRESENTATION: In this case report, we performed a combination of classical cytogenetics (G-banding), molecular cytogenetics (fluorescence in situ hybridization and X-chromosome inactivation study), and cytogenomics (microarray-based comparative genomic hybridization) techniques for characterization of an inherited (X;22) translocation in a family originally referred for infertility investigation. Both proband and his sister are infertile and present the maternally inherited translocation. Interestingly, the maternal grandmother was mosaic for X chromosome monosomy suggesting that the t(X;22) in the proband's mother arose by errors at oogenesis. The presence of the same mosaicism of the X chromosome in the proband's aunt is consistent with this consideration. Array- CGH analysis showed no constitutional pathogenic gains or losses in the translocation carriers. The X-chromosome inactivation studies revealed that the translocated X;22 was active in 99.3% of cells in the mother and in 88% of cells in the daughter. We suggest that incomplete skewing of X inactivation (>97 %) of the daughter could justify the infertility. This study is the first description of recurrent mosaicism of the X chromosome associated with a familial X-autosome translocation. CONCLUSIONS: The phenotype of infertility was probably caused by disruption of spermatogenesis due to gametogenesis specific errors resulted from meiotic pairing and segregation anomalies on the translocated chromosomes.

Smoking-induced chromosomal segregation anomalies identified by FISH analysis of sperm.

BACKGROUND: Numerical chromosome aberrations in gametes are directly related to infertility and aneuploid embryos. Previous studies have shown that toxic substances from cigarette smoke induce structural and numerical chromosomal aberrations in vitro and could potentially increase levels of aneusomy in sperm. Moreover, increased levels of aneusomy in sperm are correlated with low implantation rates, spontaneous abortions and fetal losses. Studies of chromosome 3 in sperm suggest it may be more prone to segregation anomalies than other autosomes, but there has been no systematic investigation of the incidence of disomy for chromosome 3 in sperm derived from donor male smokers. The objective of this study was to use FISH to evaluate the influence of smoking on the levels of disomy for chromosomes X and Y, and to determine whether disomy levels for chromosome 3 were elevated in sperm derived from male smokers. RESULTS: FISH analysis was used to evaluate the frequency of disomies of chromosomes 3, X, and Y in sperm of 10 smokers, compared to a control group of 7 non-smoking fertile men. All the subjects presented a normal somatic karyotype. There was a significant increase in the overall frequency of disomies in sperm derived from the smoking group (P< 0.0001). When each chromosome pair was analyzed individually, disomy of chromosome 3 in smokers was found to be more than twice that observed in the matched non-smoker control group. In addition we observed a higher frequencies of disomy of the X and Y chromosomes, indicating elevated levels of diploidy in the sperm from the smoking group. CONCLUSIONS: In this study we have shown that chromosome 3 may be susceptible to smoking-related segregation anomalies. Our results also suggest that errors can occur in both meiosis I and II, confirming the emerging literature that the male meiotic process may generally be affected by the genotoxic damage from tobacco use. Collectively, these findings provide additional evidence for enhancing tobacco control measures, and suggest that FISH analysis of chromosome 3 in sperm may be useful for monitoring smoking-induced segregation damage as part of the evaluation of infertile males.