Longitudinal large-scale changes in maternal circulating microRNAs associated with gestation-related compartments, fetal sex, and growth during and post-pregnancy.

Circulating microRNAs (c-miRNAs) during pregnancy could provide information regarding the functional status of the mother and fetus. However, it remains unclear which pregnancy-related processes are actually reflected by changes c-miRNAs. Here, we used large-scale c-miRNA profiling of maternal plasma during and post-pregnancy, and compared it with that of non-pregnant women. Fetal growth measurements and fetal sex data were used to identify associated changes in these transcripts. Surprisingly, c-miRNA subpopulations with prominent expression in maternal/fetal compartments (placenta, amniotic fluid, umbilical cord plasma and breast milk) were found to be under-expressed in circulation throughout pregnancy relative to non-pregnant plasma profiles. Furthermore, we found a bias in global c-miRNA expression in association with fetal sex right from the first trimester, in addition to a specific c-miRNA signature of fetal growth. Our results demonstrate the existence of specific temporal changes in c-miRNA populations associated with specific pregnancy-related compartments and processes, including fetal sex, and growth.

Cervicovaginal Cytokines to Predict the Onset of Normal and Preterm Labor: a Pseudo-longitudinal Study.

Inflammatory processes associated with human parturition are still not completely understood, not only because the gap between inflammation and the onset of labor has been difficult to study but also because of the limited knowledge about the role of cervicovaginal fluid (CVF) cytokines during the sequence of labor. We aimed to determine whether CVF cytokines could predict the onset of normal and preterm labor. Chemokines and proinflammatory and anti-inflammatory cytokines in CVF were measured in a pseudo-longitudinal manner in healthy women between 12 and 41 weeks gestation with intact fetal membranes before and during the first stage of labor. Women were grouped into five stages, from the absence of uterine activity and cervical changes to regular uterine contractions with cervix dilation > 3 cm (active phase of labor). Of 144 women with spontaneous labor, 96 gave birth at term, 48 gave birth preterm, and both groups displayed similar cytokine concentrations. We found positive correlations between proinflammatory cytokines and the initial sequence of labor, using individual cytokines and score-based data by principal component analysis (IFN-γ, TNF-α, IL-1ß, IL-6) as dependent variables. The risk of labor onset increased as the concentrations of IL-6 increased (hazard ratio = 202.09, 95% confidence interval = 24.57-1662.49, P < 0.001). The IL-6 concentration predicted the onset of labor within 12 days of sampling (area under the time-dependent ROC curve = 0.785, 95% confidence interval = 0.693-0.877). Here, we showed that regardless of gestational age, the onset of labor could be predicted by the IL-6 concentration in the CVF, since the initial sequence of spontaneous labor displayed an inflammatory response expressed by the increase in proinflammatory cytokines.

Influence of pre-pregnancy body mass index (p-BMI) and gestational weight gain (GWG) on DNA methylation and protein expression of obesogenic genes in umbilical vein.

Understanding the regulatory mechanisms that affect obesogenic genes expression in newborns is essential for early prevention efforts, but they remain unclear. Our study aimed to explore whether the maternal p-BMI and GWG were associated with regulatory single-locus DNA methylation in selected obesogenic genes. For this purpose, DNA methylation was assayed by Methylation-Sensitive High Resolution Melting (MS-HRM) technique and Sanger allele-bisulfite sequencing in fifty samples of umbilical vein to evaluate glucosamine-6-phosphate deaminase 2 (GNPDA2), peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), and leptin receptor (LEPR) genes. Correlations between DNA methylation levels and indicators of maternal nutritional status were carried out. Western blotting was used to evaluate protein expression in extracts of the same samples. Results indicated that GNPDA2 and PGC1α genes have the same level of DNA methylation in all samples; however, a differential DNA methylation of LEPR gene promoter was found, correlating it with GWG and this correlation is unaffected by maternal age or unhealthy habits. Furthermore, leptin receptor (Lep-Rb) was upregulated in samples that showed the lowest levels of DNA methylation. This study highlights the association between poor GWG and adjustments on obesogenic genes expression in newborn tissues with potential consequences for development of obesity in the future.