Epigenetic Profiling in the Saliva of Obese Pregnant Women.

Maternal obesity is associated with inflammation and oxidative stress, strongly impacting the intrauterine environment with detrimental consequences for both mother and offspring. The saliva is a non-invasive biofluid reflecting both local and systemic health status. This observational study aimed to profile the epigenetic signature in the saliva of Obese (OB) and Normal-Weight (NW) pregnant women. Sixteen NW and sixteen OB Caucasian women with singleton spontaneous pregnancies were enrolled. microRNAs were quantified by the OpenArray Platform. The promoter region methylation of Suppressor of Cytokine Signaling 3 (SOCS3) and Transforming Growth Factor Beta 1 (TGF-Beta1) was assessed by pyrosequencing. There were 754 microRNAs evaluated: 20 microRNAs resulted in being differentially expressed between OB and NW. microRNA pathway enrichment analysis showed a significant association with the TGF-Beta signaling pathway (miTALOS) and with fatty acids biosynthesis/metabolism, lysine degradation, and ECM-receptor interaction pathways (DIANA-miRPath). Both SOCS3 and TGF-Beta1 were significantly down-methylated in OB vs. NW. These results help to clarify impaired mechanisms involved in obesity and pave the way for the understanding of specific damaged pathways. The characterization of the epigenetic profile in saliva of pregnant women can represent a promising tool for the identification of obesity-related altered mechanisms and of possible biomarkers for early diagnosis and treatment of pregnancy-adverse conditions.

Titanium and Zirconium Levels Are Associated with Changes in MicroRNAs Expression: Results from a Human Cross-Sectional Study on Obese Population.

OBJECTIVES: In this study on 90 individuals we aimed at evaluating the microRNAs (miRNAs) expression profile associated with personal levels of Titanium (Ti) and Zirconium (Zr) traced in hair samples. Ti and Zr materials are broadly used for dental implants but the biological reactions triggered by a long term presence of these materials in the oral cavity still need to be assessed. MiRNAs are mechanisms that need to be investigated as they play a fundamental role in the control of gene expression following external stimuli and contribute to a wide range of pathophysiological processes. METHODS: Using the TaqMan® Low-Density Array, we assessed the expression levels of 377 human miRNAs in peripheral blood of 90 subjects. Hair samples were analyzed for Ti and Zr content using Inductively Coupled Plasma-Mass Spectrometry. We performed multivariable regression analysis to investigate the effects of Ti and Zr exposure on miRNA expression levels. We used the Ingenuity Pathway Analysis (IPA) software to explore the functional role of the investigated miRNAs and the related target genes. RESULTS: Seven miRNAs (miR-99b, miR-142-5p, miR-152, miR-193a-5p, miR-323-3p, miR-335, miR-494) resulted specifically associated with Zr levels. The functional target analysis showed that miRNAs are involved in mechanisms such as inflammation, skeletal and connective tissue disorders. CONCLUSIONS: Our data suggest that Zr is more bioactive than Ti and show that miRNAs are relevant molecular mechanisms sensitive to Zr exposure.

Effects of short-term exposure to inhalable particulate matter on telomere length, telomerase expression, and telomerase methylation in steel workers.

BACKGROUND: Shortened leukocyte telomere length (LTL) is a marker of cardiovascular risk that has been recently associated with long-term exposure to ambient particulate matter (PM). However, LTL is increased during acute inflammation and allows for rapid proliferation of inflammatory cells. Whether short-term exposure to proinflammatory exposures such as PM increases LTL has never been evaluated. OBJECTIVES: We investigated the effects of acute exposure to metal-rich PM on blood LTL, as well as molecular mechanisms contributing to LTL regulation in a group of steel workers with high PM exposure. METHODS: We measured LTL, as well as mRNA expression and promoter DNA methylation of the telomerase catalytic enzyme gene [human telomerase reverse transcriptase (hTERT)] in blood samples obtained from 63 steel workers on the first day of a workweek (baseline) and after 3 days of work (postexposure). RESULTS: LTL was significantly increased in postexposure (mean ± SD, 1.43 ± 0.51) compared with baseline samples (1.23 ± 0.28, p-value < 0.001). Postexposure LTL was positively associated with PM10 (ß = 0.30, p-value = 0.002 for 90th vs. 10th percentile exposure) and PM1 (ß = 0.29, p-value = 0.042) exposure levels in regression models adjusting for multiple covariates. hTERT expression was lower in postexposure samples (1.31 ± 0.75) than at baseline (1.68 ± 0.86, p-value < 0.001), but the decrease in hTERT expression did not show a dose-response relationship with PM. We found no exposure-related differences in the methylation of any of the CpG sites investigated in the hTERT promoter. CONCLUSIONS: Short-term exposure to PM caused a rapid increase in blood LTL. The LTL increase did not appear to be mediated by PM-related changes in hTERT expression and methylation.