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.

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.