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.