Dysregulation of Placental miRNA in Maternal Obesity Is Associated With Pre- and Postnatal Growth

Maternal obesity and nutrient excess in utero increase the risk of future metabolic diseases. The mechanisms underlying this process are poorly understood, but probably include genetic, epigenetic alterations and changes in fetal nutrient supply. Placenta, and particularly amniotic fluid, is the in utero environment that could modify fetal growth and adiposity by exerting stimulatory or inhibitory effects on fetal genome expression. Examples of epigenetic mechanisms are DNA methylation, histone modifications and microRNAs (miRNAs). miRNAs are a class of noncoding endogenous RNA molecules approximately 22 nucleotides long that regulate gene expression at the transcriptional or posttranscriptional level by suppressing translation of protein coding genes or cleaving target mRNAs to induce their degradation. The expression of placental miRNAs is altered during pregnancy in such pathological conditions as preeclampsia, small-for-gestational-age newborns and fetal congenital heart defects, but their role in obesity has not yet been investigated. It is known that miRNAs regulate gene expression in the amniotic fluid during obesity and the expression profile of miRNAs is altered in maternal obesity. This study highlights the fact that the placenta responds to the maternal obesogenic environment by expressing a specific placental miRNA profile. The authors identified eight placenta obesity-associated miRNAs, four of which (miR-100, miR-1285, miR-296, and miR-487) were related to prenatal and postnatal growth parameters. Among them, miR-296 was present in second-trimester plasma samples and was associated with placental expression as well as with prenatal and postnatal growth. These miRNAs were associated with metabolic parameters, predictors of lower birth weight and increased postnatal weight gain. From a functional point of view these miRNAs were related to cell proliferation and insulin signaling pathways. Interestingly not all the miRNA’s in the placenta were detectable in the maternal serum.