Abstract Body
As the master regulator of early development, the placenta is responsible for initiating changes in maternal physiology to sustain pregnancy as well as promoting fetal growth and development. MicroRNAs (miRNAs) are epigenetic post-transcriptional regulators of gene expression which participate in critical processes during early development, including embryogenesis, implantation and placentation. Cadmium is an environmental toxicant with no known biological role in humans. Human exposure primarily occurs through consumption of contaminated food or through the use of tobacco products. Gestational cadmium exposure has been associated with adverse health outcomes in newborns, but the molecular mechanisms by which these are initiated remain unclear. In this study, 281 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) were selected for trace element profiling and small RNA transcriptomic analysis. We identified four differentially expressed placental miRNAs (DEmiRs) were significantly associated with cadmium concentrations in placenta (FDR <0.1): miR-509-3p, miR-10b-5p, miR-10b-3p, and miR-193b-5p. For two of these four DEmiRs (miR-509-3p and miR-193b-5p), the direction of effect was consistent in an independent analysis within the Rhode Island Child Health Study (RICHS)(n=115) but were not significantly associated with placental cadmium concentrations. Bioinformatic miRNA target prediction was used to identify potential mRNAs targeted by these DEmiRs, revealing gene targets participating in various cell signaling pathways critical for placentation, angiogenesis and response to hypoxia. These results indicate that accumulation of cadmium within the placenta may disrupt fetoplacental gene expression via changes in miRNAs. Future work aims to identify associations between early life health outcomes and differential expression of cadmium-sensitive fetoplacental miRNAs.
