LncRNA Tuna is activated in cadmium-induced placental insufficiency and drives the NRF2-mediated oxidative stress response [mouse]
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PROVIDER: PRJNA975566 | ENA |
REPOSITORIES: ENA
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Project description: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.InuteroCd 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 CdCl2 and performed RNA-seq on control and CdCl2 exposed placentae. The top differentially expressed transcript was the Tcl1Upstream Neuron-Associated (Tuna) long non-coding RNA, which was up-regulated over 25-fold in CdCl2 exposed placentae. Tuna has been shown to be critical for neural stem cell differentiation. However, within the placenta, there is no evidence that Tuna is normally expressed or functional at any developmental stage. To determine the spatial expression of Cd-activated Tuna within the placenta, we used in situ hybridization as well as placental layer-specific RNA isolation and analysis. Both methods confirmed the absence of Tuna expression in control samples and determined that Cd-induced Tuna expression is specific to the junctional zone. Since many lncRNAs regulate gene expression, we hypothesized that Tunaforms part of the mechanism of Cd-induced transcriptomic changes. To test this, we over-expressed Tuna in cultured choriocarcinoma cells and compared gene expression profiles to those of control and CdCl2 exposed cells. We demonstrate significant overlap between genes activated byTunaoverexpression and genes activated by CdCl2 exposure, with enrichment in the NRF2-mediated oxidative stress response. Herein we analyze the NRF2 pathway and show that Tuna increases NRF2/NRF2 both at the transcript and protein levels. Tuna drives increased NRF2 target gene expression, a result that is abrogated with the use of an NRF2 inhibitor, confirming that Tuna activates oxidative stress response genes through this pathway. This work identifies the lncRNA Tuna as a potential novel player in Cd-induced placental insufficiency.
2023-05-31 | GSE233252 | GEO
Project description: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.InuteroCd 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 CdCl2 and performed RNA-seq on control and CdCl2 exposed placentae. The top differentially expressed transcript was the Tcl1Upstream Neuron-Associated (Tuna) long non-coding RNA, which was up-regulated over 25-fold in CdCl2 exposed placentae. Tuna has been shown to be critical for neural stem cell differentiation. However, within the placenta, there is no evidence that Tuna is normally expressed or functional at any developmental stage. To determine the spatial expression of Cd-activated Tuna within the placenta, we used in situ hybridization as well as placental layer-specific RNA isolation and analysis. Both methods confirmed the absence of Tuna expression in control samples and determined that Cd-induced Tuna expression is specific to the junctional zone. Since many lncRNAs regulate gene expression, we hypothesized that Tunaforms part of the mechanism of Cd-induced transcriptomic changes. To test this, we over-expressed Tuna in cultured choriocarcinoma cells and compared gene expression profiles to those of control and CdCl2 exposed cells. We demonstrate significant overlap between genes activated byTunaoverexpression and genes activated by CdCl2 exposure, with enrichment in the NRF2-mediated oxidative stress response. Herein we analyze the NRF2 pathway and show that Tuna increases NRF2/NRF2 both at the transcript and protein levels. Tuna drives increased NRF2 target gene expression, a result that is abrogated with the use of an NRF2 inhibitor, confirming that Tuna activates oxidative stress response genes through this pathway. This work identifies the lncRNA Tuna as a potential novel player in Cd-induced placental insufficiency.
2023-05-31 | GSE233281 | GEO
Project description:LncRNA Tuna is activated in cadmium-induced placental insufficiency and drives the NRF2-mediated oxidative stress response.
| PRJNA975619 | ENA
Project description:LncRNA Tuna is activated in cadmium-induced placental insufficiency and drives the NRF2-mediated oxidative stress response [human Jeg3]
| PRJNA975622 | ENA
Project description:Intrauterine growth restriction (IUGR) represents a major obstetric challenge with perinatal complications and a risk factor of developing disease in adult life. Placental insufficiency is one of the common features accompanying IUGR. The aim of this study was to evaluate global placental gene expression profile in IUGR compared to normal pregnancies. Placental samples were collected by eight IUGR pregnancies with placental insufficiency ascertained by Doppler and eight healthy controls. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate global gene expression profile. Principal component analysis showed good separation in terms of gene expression patterns between the groups. Pathway analysis with Bonferroni correction for multiple testing showed significant (p<0.05) up-regulation of inflammation mediated by chemokine and cytokine signalling pathway in the IUGR placentas. Genes involved in metabolism of glucocorticoids (HSD11B1 and DHRS2) were found differentially expressed. We found no imprinted genes to be differentially expressed and only one gene involved in epigenetic modifications (MBD3) to be down-regulated in the IUGR placentas, indicating that IUGR due to placental insufficiency is not associated to placental imprinting. Subgroup analysis between pure IUGR and IUGR with preeclampsia placentas showed only 27 differentially expressed genes suggesting common pathophysiology. Eight placental samples from normal human placenta compared to eight human placental samples from patients with intrauterine growth restrictions due to placental insufficiency
2008-08-01 | E-GEOD-12216 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-05-31 | GSE233282 | GEO
Project description:Intrauterine growth restriction (IUGR) represents a major obstetric challenge with perinatal complications and a risk factor of developing disease in adult life. Placental insufficiency is one of the common features accompanying IUGR. The aim of this study was to evaluate global placental gene expression profile in IUGR compared to normal pregnancies. Placental samples were collected by eight IUGR pregnancies with placental insufficiency ascertained by Doppler and eight healthy controls. A 30K Human Genome Survey Microarray v.2.0 (Applied Biosystems) was used to evaluate global gene expression profile. Principal component analysis showed good separation in terms of gene expression patterns between the groups. Pathway analysis with Bonferroni correction for multiple testing showed significant (p<0.05) up-regulation of inflammation mediated by chemokine and cytokine signalling pathway in the IUGR placentas. Genes involved in metabolism of glucocorticoids (HSD11B1 and DHRS2) were found differentially expressed. We found no imprinted genes to be differentially expressed and only one gene involved in epigenetic modifications (MBD3) to be down-regulated in the IUGR placentas, indicating that IUGR due to placental insufficiency is not associated to placental imprinting. Subgroup analysis between pure IUGR and IUGR with preeclampsia placentas showed only 27 differentially expressed genes suggesting common pathophysiology.
2008-08-01 | GSE12216 | GEO
Project description:We analyzed differences in placental gene expressions. We examined the mRNA expression profile in placental labyrinth zone from normal pregnant mice, and PAH mice with different Nrf2 expressions (WT, Nrf2 Knockout [KO], Keap1 Knockdown [KD])
2017-01-01 | GSE76669 | GEO
Project description:Goal: To test the long-term influence of placental allopregnanolone (ALLO) loss on mouse brain transcriptome, in a sex- and region-specficic manner. Methods: We deleted the gene encoding the synthetic enzyme for ALLO (Akr1c14) specifically in trophoblasts by crossing Akr1c14-floxed mice with Cyp19a-Cre mice (plKO mice). Region-specific mRNA profiles of 30-day old WT and plKO mice were generated by 3'mRNA sequencing, in triplicate, using Illumina HiSeq 2500. Results: Our RNA sequencing analysis reveals that placental ALLO withdrawal is associated with region- and sex-specific gene expression changes. The differentially expressed genes are notably associated with myelination and autism spectrum disorders. Conclusions: We show that placental ALLO insufficiency is associated with long-term changes in gene expression in the mouse brain in a sex- and region-specific manner.
2021-04-28 | GSE173440 | GEO