Data for Dysregulation of human placental microRNAs by gestational cadmium exposure is implicated in neurobehavioral outcomes at birth

Background: Prenatal cadmium (Cd) exposure has been implicated in both placental toxicity and adverse neurobehavioral outcomes. Placental microRNAs (miRNAs) may function to developmentally program adverse pregnancy and newborn health outcomes in response to gestational Cd exposure. Methods: In a subset of the Rhode Island Child Health Study (RICHS, n=115) and the New Hampshire Birth Cohort Study (NHBCS, =281), we used small RNA sequencing and trace metal analysis to identify Cd-associated expression of placental miRNAs using negative binomial generalized linear models. We characterized the inter-relationships of Cd-associated miRNAs, their predicted mRNA targets, and neurobehavioral outcomes at birth through the integration of transcriptomic data and summary scores from the NICU Network Neurobehavioral Scale (NNNS). Results: Placental Cd concentrations are associated with the expression of five placental miRNAs in NHBCS, with similar directions and effect sizes in RICHS. The targets of these miRNA are overrepresented in nervous system development, and are associated with NNNS metrics suggestive of atypical neurobehavioral outcomes at birth. Conclusions: Gestational Cd exposure is associated with the expression of placental miRNAs. Predicted targets of these miRNAs are involved in nervous system development and may also regulate placental physiology, allowing their dysregulation to initiate developmental programming of newborn and early life health outcomes.