Long-term impact of placental allopregnanolone insufficiency on the mouse transcriptome of cerebral cortex, hippocampus, hypothalamus and cerebellum
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ABSTRACT:
PROVIDER: PRJNA725533 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14336800.fastq.gz | Fastqsanger.gz | |||
| SRR14336801.fastq.gz | Fastqsanger.gz | |||
| SRR14336802.fastq.gz | Fastqsanger.gz | |||
| SRR14336803.fastq.gz | Fastqsanger.gz | |||
| SRR14336804.fastq.gz | Fastqsanger.gz |
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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
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:The hypothalamus is a key site for the integration of the response to nutrient deprivation in higher organisms. Transcripts that are dynamically regulated in the hypothalamus by feeding and fasting are likely to play a regulatory role in energy balance. In order to identify hypothalamic genes whose expression is altered by fasting, we compared the transcriptomes of hypothalamic blocks from freely feeding vs overnight fasted mice using whole genome oligonucleotide arrays. In order to exclude changes due to non-specific neuronal stress responses to energy deprivation we simultaneously profiled the cerebellum, a brain site with no known regulatory role in energy balance. The power of this approach was illustrated by the fact that while we confirmed previous observations that the Sulfotransferase family 1A gene is upregulated by fasting in the hypothalamus, we showed that it was similarly upregulated in the cerebellum and is therefore unlikely to be specifically involved in the regulation of energy balance. In contrast, using three different methods of pathway enrichment analysis, multiple genes involved in mitochondrial oxidative phosphorylation were found to be co-ordinately downregulated by fasting in the hypothalamus but not in the cerebellum. These findings suggest that a switch from oxidative to non-oxidative metabolism in the hypothalamus may be an important element of the homeostatic response to nutrient deprivation. Keywords: hypothalamus, cerebellum, fasting, appetite, obesity
2007-02-09 | GSE4221 | 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:The etiology of fetal growth restriction (FGR) is multifactorial, although many cases often involve placental insufficiency. Placental insufficiency is associated with inadequate trophoblast invasion that results in an environment with high resistance to blood flow, decreased availability of nutrients to the placenta, and increased hypoxia. Despite accumulating knowledge linking inadequate trophoblast invasion with placental insufficiency and FGR, current treatment options are limited to iatrogenic delivery, usually preterm. We have developed a non-viral, polymer-based nanoparticle that facilitates transient human insulin-like 1 growth factor (hIGF1) gene delivery specifically to placental trophoblast. Using the established guinea pig maternal nutrient restriction (MNR) model of placental insufficiency and FGR, the aim of the study was to identify novel pathways in the sub-placenta/decidua that will provide insight into the underlying mechanism driving FGR, and may be corrected with hIGF1 nanoparticle treatment. Pregnant guinea pig dams underwent ultrasound-guided sham or hIGF1 nanoparticle treatment at mid-pregnancy, and sub-placenta/decidua tissue was collected 5 days later. Transcriptome analysis was performed using RNA Sequencing on the Illumina platform. Histological assessment of the sub-placenta/decidua demonstrated fewer maternal spiral arteries lined by trophoblast in the MNR sub-placenta/decidua which was associated with downregulation of genes involved in epithelium development and the regulation of cell migration. hIGF1 nanoparticle treatment results in marked changes to transporter activity in the MNR + hIGF1 sub-placenta/decidua when compared to sham MNR. Under normal growth conditions however, hIGF1 nanoparticle treatment in Control + hIGF1 sub-placenta/decidua was associated with downregulation of kinase signaling and increased proteolysis indicative of homeostasis. Overall, this study identified changes to the sub-placenta/decidua transcriptome that likely result in inadequate trophoblast invasion and that contribute to placental insufficiency. Additionally, this study has increased our understanding of pathways that hIGF1 nanoparticle treatment acts on in order to restore or maintain appropriate placenta function.
2025-03-26 | GSE269098 | GEO
Project description:Fetal growth restriction (FGR) affects between 5-10% of all live births. Placental insufficiency is a leading cause of FGR, resulting in reduced nutrient and oxygen delivery to the fetus. Currently, there is no effective in utero treatment options for FGR, or placental insufficiency. We have developed a gene therapy to deliver human insulin-like 1 growth factor (hIGF1) to the placenta via a non-viral nanoparticle delivery mechanism as potential treatment of FGR. Using a guinea pig maternal nutrient restriction (MNR) model of FGR, we aimed to understand the transcriptional changes within the placenta associated with placental insufficiency that occur at the beginning stages of FGR (mid-pregnancy), and the immediate impact of hIGF1 nanoparticle treatment on the placental transcriptome. Using RNAsequencing, we analyzed protein coding genes of three experimental groups: Control dams and MNR receiving a sham treatment, and MNR dams receiving hIGF1 nanoparticle treatment. Pathway enrichment analysis comparing MNR placentas to Control revealed upregulation of pathways associated with degradation and repair of genetic information and downregulation of pathways associated with transmembrane transport. Similarly, differentially expressed genes that were decreased in MNR + hIGF1 placentas compared to Control demonstrated downregulation in pathways relating to transporter activities, but upregulation in pathways associated with positive regulation of phosphorylation and kinase activity. When compared to MNR placentas, MNR + hIGF1 placentas demonstrated changes to genes associated with transmembrane transporter activity including ion, vitamin and solute carrier (SLC-mediated) transport. Overall, this study identifies the key signaling and metabolic changes occurring in the placenta that contribute to placental insufficiency, and increases our understanding of the pathways that increasing placental IGF1 expression acts on and corrects.
2025-03-26 | GSE269097 | GEO
Project description:We describe age-related molecular and neuronal changes that disrupt mobility or energy balance based on brain region and genetic background. Compared to young mice, aged C57BL/6 mice exhibit marked locomotor (but not energy balance) impairments. In contrast, aged BALB mice exhibit marked energy balance (but not locomotor) impairments. Age-related changes in cerebellar or hypothalamic gene expression accompany these phenotypes. Aging evokes upregulation of immune pattern recognition receptors and cell adhesion molecules. However, these changes do not localize to microglia, the major CNS immunocyte. Consistent with a neuronal role, there is a marked age-related increase in excitatory synapses over the cerebellum and hypothalamus. Functional imaging of these regions is consistent with age-related synaptic impairments. These studies suggest that aging reactivates a developmental program employed during embryogenesis where immune molecules guide synapse formation and pruning. Renewed activity in this program may disrupt excitatory neurotransmission, causing significant behavioral deficits. keywords: aging, C57BL/6, BALB, CBA, hypothalamus, cerebellum, striatum, frontal cortex
2016-09-20 | GSE87102 | GEO
Project description:Malnutrition in women of childbearing age is associated with an increased risk of fetal growth restriction and poor infant development. Climate change, specifically the rise in ambient temperature, is thought to exacerbate the effects of malnutrition. However, few mechanistic studies exist to examine the interactions between maternal nutrition and ambient temperature on fetal growth. Here we develop a novel animal model of marginal micronutrient insufficiency and modest heat stress during pregnancy to understand interactive effects on fetal growth in mice. Female C57BL6/J mice (8 wk old, n = 6-8/group) were given ad libitum access to either AIN-93G (CON) or a modified AIN-93 diets containing 70% mineral, micronutrient, and vitamin mix (70MMV) for 4 weeks. After breeding females were housed at either 22⁰C or 33⁰C in an environmental chamber for the duration of pregnancy while remaining on their respective diets. Mice fed 70MMV diet had significantly reduced body weight gains during pregnancy in comparison to CON diet fed group. Serum K, Fe, Zn, and Se levels showed reduced levels either by diet or temperature. A novel interaction between modest heat and micronutrient insufficiency was identified and led to an altered placenta transcriptome and fetal growth restriction in this model. Sexually dimorphic differences were observed in placental and fetal tissues in the temperature groups. In males, placenta gene expression related to vascularization, nutrient transport, and stress-related responses (i.e. ER stress and inflammation) were impacted in the combination group exposed to 70MMV diet and elevated temperature, while in females the same biological functions were affected only in the CON-33C group. Collectively, our results point to an interaction between modest heat and micronutrient insufficiency on placental dysfunction and the pathogenesis of fetal growth restriction, highlighting the emerging nexus of maternal nutrition and heat stress typically seen in resource-restrained settings.
2025-09-25 | GSE278025 | 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 | 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