Cadmium (Cd) is a toxic heavy metal found throughout the environment and one of the top ten toxicants of major public health concern identified by the World Health Organization.In uteroCd exposure causes fetal growth restriction, malformation, and spontaneous abortion; however, the mechanisms by which Cd impacts these outcomes are poorly understood. Cd accumulates in the placenta, suggesting that these negative outcomes may be a consequence of disrupted placental function and placental insufficiency. To understand the impact of Cd on gene expression within the placenta, we developed a mouse model of Cd-induced fetal growth restriction through maternal consumption of CdCl2and performed RNA-seq on control and CdCl2exposed placentae. The top differentially expressed transcript was theTcl1 Upstream Neuron-Associated(Tuna) long non-coding RNA, which was upregulated over 25-fold in CdCl2exposed placentae.Tunahas been shown to be critical for neural stem cell differentiation. However, within the placenta, there is no evidence thatTunais normally expressed or functional at any developmental stage. To determine the spatial expression of Cd-activatedTunawithin the placenta, we usedin situhybridization as well as placental layer-specific RNA isolation and analysis. Both methods confirmed the absence ofTunaexpression in control samples and determined that Cd-inducedTunaexpression is specific to the junctional zone. Since many lncRNAs regulate gene expression, we hypothesized thatTunaforms part of the mechanism of Cd-induced transcriptomic changes. To test this, we over-expressedTunain cultured choriocarcinoma cells and compared gene expression profiles to those of control and CdCl2exposed cells. We demonstrate significant overlap between genes activated byTunaoverexpression and genes activated by CdCl2exposure, with enrichment in the NRF2-mediated oxidative stress response. Herein we analyze the NRF2 pathway and show thatTunaincreasesNRF2/NRF2 both at the transcript and protein levels.Tunadrives increased NRF2 target gene expression, a result that is abrogated with the use of an NRF2 inhibitor, confirming thatTunaactivates oxidative stress response genes through this pathway. This work identifies the lncRNATunaas a potential novel player in Cd-induced placental insufficiency.