Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA249057 | ENA |
REPOSITORIES: ENA
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Project description:Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured biomarker inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1-/-), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75 or 0.85 mg/kg/d CPO from gestational days (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), RBC acylpeptide hydrolase (APH), plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1-/- and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1-/- mice, but not in other genotypes.
2014-08-04 | GSE58103 | GEO
Project description:Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured biomarker inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1-/-), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75 or 0.85 mg/kg/d CPO from gestational days (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), RBC acylpeptide hydrolase (APH), plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1-/- and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1-/- mice, but not in other genotypes. Pregnant mice (wild type (WT), PON1-knockout (KO), tgHuPON1R192 (R-tg) and tgHuPON1Q192 (Q-tg)) were exposed to various amounts of CPO (0, 0.5, 0.75 and 0.85 mg/kg/d) for 12 days (gestational days 6-17). On gestational day 18, dams were sacrificed and fetal brains were collected. A total of 264 fetal brains from 80 dams were processed to extract total RNA using TRIZOL and the QIAamp Tissue kit from QIAGEN. Microarray analysis was performed using the fetuses of 5 dams per experimental group (total RNA was pooled from individual fetal brains from each dam). The dams used for fetal-brain microarray analysis were selected using a random-number generator, after first eliminating dams with brain AChE activities > 1.5 SD compared to the mean for their treatment group. RNA samples isolated from individual fetal brains from each dam were combined, then labeled and hybridized to Affymetrix Mouse Gene 1.0 ST microarrays.
2014-08-04 | E-GEOD-58103 | biostudies-arrayexpress
Project description:Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice. Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO).
2011-11-09 | GSE25250 | GEO
Project description:Chlorpyrifos (CPF) is an organophosphorus (OP) insecticide that is still widely used despite statutory restrictions on home use. CPF is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. Paraoxonase (PON1) polymorphisms affects the catalytic efficiency of the hydrolysis of OPs, including CPO. We used both wt (PON1+/+) and PON1 knockout (PON1-/-) mice and PON1-/- mice carrying transgenes encoding the human alloforms tgHuPON1Q192 and tgHuPON1R192 to gain insight into the mechanisms of neurotoxicity of CPO throughout postnatal development, and to ascertain the importance of the PON1Q192R polymorphism for protecting against developmental toxicity of CPO. Whole-genome microarrays were used to measure gene expression changes associated with chronic CPO exposure of developing (PND 4-21) PON1-/-, tgHuPON1Q192R transgenic and PON1+/+ mice. Expression profiles are derived from cerebella from wild-type C57/Bl6 and PON1-/- on a C57/Bl6 background and two transgenic strains (tgHuPON1Q192, tgHuPON1R192) expressing either human PON1Q192 or human PON1R192 on the PON1-/- C57/Bl6 background. The mice were subjected to chronic postnatal exposure to CPO (CPO). Transgenic, PON1-KO and WT neonatal mice either treated with control (DMSO), 0.35 mg*kg-1*day-1 CPO or 0.5 mg*kg-1*day-1 CPO daily from PND 4 to PND 21. Chlorpyrifos (CPF) is converted to chlorpyrifos oxon (CPO) by oxidative desulfuration in liver. 55 arrays, 12 experimental groups (strain + treatment), due to QC issues the replicates are as follows; PON1-KO-0.35 (5), PON1-KO-.O5 (3), PON1-KO-DMSO (4), PON1-Q129-0.35 (5), PON1-Q129-0.5 (5), PON1-Q129-DMSO (4), PON1-R129-0.35 (5), PON1-R129-0.5 (5), PON1-R129-DMSO (4), WT-0.35 (6), WT-0.5 (3), WT-DMSO (6)
2011-11-09 | E-GEOD-25250 | biostudies-arrayexpress
Project description:Human paraoxonase-1 (PON1) is an enzyme with lactonase, esterase and phosphotriesterase activity that has been associated with multiple phenotypes. We expressed hPON1 ubiquitously in Drosophila melanogaster using the Gal4 system Tub driver.
2011-05-26 | GSE29534 | GEO
Project description:Compairsion of transcriptional profiles of heart and skeletal muscle tissue of fetal rhesus monkey exposed to maternal Bisphenol A or vehicle during early or late gestaion. Maternal exposure to the endocrine disrupting chemical, bisphenol A (BPA) affects the development of multiple organ systems in rodents and monkeys. However, effects of BPA exposure on cardiac and skeletal muscle development have not been assessed. Given that maternal BPA crosses placenta and reaches developing fetus, examining the physiological consequences of gestational exposure during development is of research significance. Therefore, we evaluate the effects of daily, oral BPA exposure of pregnant rhesus monkeys (Macaca mulatta) on the fetal heart and skeletal muscle transcriptome. Pregnant monkeys were administered daily oral doses (400 µg/kg body weight) of BPA during early (50 –100 ± 2 days post conception, dpc) or late (100 ± 2 dpc - term), gestation. At the end of treatment, fetal heart tissues; left ventricle (LV), right ventricle (RV), left atrium (LA), right atrium (RA) and skeletal muscle; biceps femoris (BFM), were collected. Transcriptome expression was assessed using genome-wide microarray in each of the tissues and compared paired-wise between the BPA and matched control fetuses. Our results show that maternal BPA exposure alters transcriptional profile of several coding and non-coding genes in fetal heart and skeletal muscle.
2014-07-01 | GSE53393 | GEO
Project description:Infection-associated inflammatory stress during pregnancy is the most common cause of fetal growth restriction. Treatment strategies for protection of at-risk mothers are limited. Employing mouse models, we demonstrate that oral treatment during pregnancy with a microbial-derived immunomodulator (OM85), markedly reduces risk for fetal loss/growth restriction resulting from maternal challenge with bacterial LPS or influenza. Focusing on LPS exposure, we demonstrate that the key molecular indices of maternal inflammatory stress (RANTES, MIP-1a, CCL2, KC, G-CSF) in gestational tissues/serum, are abrogated by OM85 pretreatment. Systems-level analyses of RNASeq data revealed that OM85 pretreatment selectively tunes LPS-induced activation in maternal gestational tissues for attenuated expression of TNF-, IL1-, and IFNg- driven proinflammatory networks, without constraining Type1-IFN-associated networks central to first-line anti-microbial defense. This study suggests that broad-spectrum protection-of-pregnancy against infection-associated inflammatory stress, without compromising capacity for efficient pathogen eradication, represents an achievable therapeutic goal.
2016-10-24 | GSE85414 | GEO
Project description:Background: Maternal Western diet (WD) consumption during pregnancy is linked to adverse gestational and offspring metabolic outcomes. Dimethyl fumarate (DMF), a Nrf2 activator with antioxidant and anti-inflammatory properties, is a proposed therapeutic candidate, but its safety and efficacy during pregnancy remain unexplored. This pilot study aimed to establish a guinea pig model of gestational WD consumption and evaluate the feasibility of DMF treatment on maternal, placental, and fetal outcomes. Methods: Pregnant guinea pigs consuming a modified WD were randomized to receive either DMF or vehicle beginning at gestational day 19. Maternal weight, urinalysis, blood glucose, and ketones were monitored weekly. Dams were sacrificed near-term and placental and fetal biometric measures were recorded. The placenta was evaluated for a panel of antioxidant and angiogenic candidate genes via RT-qPCR, and maternal and fetal livers were assessed for triglyceride content, histopathology, and transcriptomic changes via RNA-sequencing. Results: DMF did not alter maternal weight, blood glucose, urinalysis, nor fetal or placental gross outcomes. Hepatic triglyceride concentrations were unaffected in both dams and fetuses. WD consumption resulted in maternal hepatic glycogen accumulation and mild vacuolar hepatopathy without fibrosis, while fetal livers exhibited microvesicular hepatopathy and abundant extramedullary hematopoiesis without fibrosis, irrespective of treatment. Placental RT-qPCR revealed that exposure to DMF led to a decrease in transcription of Sod1 (p = 0.046) and a tendency to decrease transcription of Hmgcr (p = 0.071) and Nqo1 (p = 0.067) with no changes in other measured genes. RNA-sequencing identified 38 differentially expressed genes (DEG) in maternal livers suggesting some immune suppression and induction of P450 pathway. Fetal hepatic RNA-sequencing identified 51 DEG, distinctly different from maternal DEG, indicating an activation of interleukin 12 production. Distinct differences between fetal and maternal liver transcriptomic profiles were evident, with over 9,000 DEG (65% of annotated transcripts). Dimethyl fumarate conferred no measurable benefit on maternal or fetal hepatopathy and had a paradoxical effect in lowering placental Sod1 gene expression, but, importantly, no overt harm was appreciated. These findings establish the feasibility of a gestational guinea pig WD model and gestational DMF therapy and provide initial insights into maternal-fetal responses to DMF, most notably highlighting divergent hepatic programming between dams and offspring. Future research should assess whether DMF or related Nrf2 activators can be developed as pregnancy therapeutics, explore interactions between antioxidants and placental angiogenesis, and determine long-term offspring outcomes after exposure to WD and DMF during gestational development.
2025-12-04 | GSE312339 | GEO
Project description:Cannabis use during pregnancy is associated with adverse neurodevelopmental outcomes. However, the underlying mechanisms and effects of cannabis on fetal development are relatively unknown. We determined the impact of chronic delta-9-tetrahydrocannabinol (THC, cannabis’s main psychoactive component) exposure on fetal development in a rhesus macaque model using advanced imaging combined with molecular and tissue studies. Animals were divided into control (n=5) or THC-exposed (n=5) groups, which received a daily THC edible pre-conception and throughout pregnancy. Animals underwent fetal brain T2-weighted MRI at gestational days 85 (G85), G110, G135 and G155 (term is ~G168) to assess brain development. All animals underwent cesarean delivery with fetal cerebral spinal fluid (CSF) and brain collection at G155 for microRNA (miRNA) and histologic analysis. THC exposure did not demonstrate any fetal brain volumetric changes. However, histological findings in THC-exposed brains suggested brain dysregulation that may have long-term developmental implications. We identified two extracellular-vesicle-associated miRNAs (mir-448 and mir-199a-3p) with>2-fold change in CSF with maternal THC use. Amniotic fluid (AF) was collected at the 4 gestational ages (GA) and relative protein abundance changes measured with isobaric labeling quantitative proteomics. Changes in AF were observed across the GAs and in response to THC-treatment.
2025-07-18 | PXD042447 | Pride