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: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:In the context of male reproductive health, epidemiological studies have observed reduced testis size and abnormal sperm counts and morphology in adult men exposed in utero, although these findings are not always repeated. The ambiguity of these reports is confounded by a lack of controlled animal studies investigating the effects of maternal cigarette smoke exposure on male offspring reproductive health. In this study we examined the effects of cigarette induced reproductive toxicity on male offspring exposed during the gestational and weaning period using our novel direct nasal exposure mouse model of cigarette smoke-induced chronic obstructive pulmonary disease and female subfertility. This was done too gain a better understanding of the adverse effects of gestational maternal smoking on male offspring fertility.
2013-10-23 | GSE51530 | GEO
Project description:Adolescent binge alcohol exposure has been previously shown to have long-lasting effects on the expression of hypothalamic genes that regulate the stress response, even in the absence of subsequent adult alcohol exposure. Those data suggested that alcohol can induce permanent gene expression changes, potentially through epigenetic modifications. Importantly, epigenetic modifications can be transmitted to future generations therefore, in these studies we investigated the effects of adolescent binge alcohol exposure on hypothalamic gene expression patterns in the F1 generation offspring. It has been well documented that maternal alcohol exposure during fetal development can have devastating neurological consequences. However, less is known about the consequences of maternal and/or paternal alcohol exposure outside of the gestational time frame. Here, we exposed adolescent male and female rats to a repeated binge EtOH exposure paradigm and then mated them in adulthood. Hypothalamic samples were taken from the offspring of these animals at postnatal day (PND) 7 and subjected to a genome-wide microarray analysis followed by qRT-PCR for selected genes. Importantly, the parents were not intoxicated at the time of mating and were not exposed to EtOH at any time during gestation therefore, the offspring were never directly exposed to EtOH. Our results showed that the offspring of alcohol-exposed parents had significant differences in the expression of hypothalamic genes that mediate neurogenesis and synaptic plasticity during neurodevelopment, genes important for directing chromatin remodeling, posttranslational modifications or transcription regulation, as well as genes involved in regulation of obesity and reproductive function. These data demonstrate that repeated binge alcohol exposure during pubertal development can potentially have detrimental effects on future offspring even in the absence of direct fetal alcohol exposure.
2014-03-19 | GSE53028 | 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:Objective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.
2014-10-25 | E-GEOD-62715 | biostudies-arrayexpress
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 M-BM-5g/kg body weight) of BPA during early (50 M-bM-^@M-^S100 M-BM-1 2 days post conception, dpc) or late (100 M-BM-1 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. Pregnant rhesus monkey were administered a daily oral dose of 400 M-NM-<g/kg. body weight of Bisphenol A (BPA) or vehicle (CON) either during early (50M-bM-^@M-^S100 M-BM-1 2 days) or late (100 M-BM-1 2 daysM-bM-^@M-^Sterm) gestation. Gene expression profiles of each of the heart chambers (left ventricle, LV; right ventricle, RV; left atrium, LA; and right atrium, RA) and skeletal muscle (biceps femoris, BFM) were analyzed using microarrays and compared between the BPA exposed and matched control fetuses. A total of 12 samples were analyzed for each tissue; LV, RV, LA, RA and BFM. This includes 6 samples at each time period (early vs. late gestation) and 3 biological replicates for each treatment (BPA, n=3; control, n=3).
2014-07-01 | E-GEOD-53393 | biostudies-arrayexpress
Project description:In utero smoke exposure has adverse consequences for the child, including premature delivery, smaller birth weight and predisposition to disease later in life. The fetal liver has major detoxifying roles in addition to orchestrating the function of multiple organ systems. Maternal smoking increases the fetal toxin burden, and is expected to cause changes in the human fetal liver physiology likely contributing to disease and disease predisposition. In this project the transcriptional response in fetal liver tissue was analysed in relation to maternal smoke exposure, fetal sex and gestational age. Total RNA, protein and DNA were consecutively extracted from the same liver biopsy of electively terminated second trimester fetal livers. Proteomic analyses on the protein fraction were performed to allow for an integrated analysis of both the transcriptional and translational changes.
2024-01-08 | E-MTAB-6103 | biostudies-arrayexpress
Project description:PFAS are persistent man-made chemicals considered to be emerging pollutants, with PFOA, PFOS, and PFHxS having associations with liver toxicity and steatosis. PFOA, PFOS, and PFHxS can undergo placental/lactational transfer, however, little is known about the impact of PFAS mixtures during the developmental window, nor maternal diet on PFAS adverse effects. It was hypothesized that gestational/lactational PFAS exposure would alter the pup liver proteome. The work herein evaluated the liver proteome in offspring, identifying potential biochemical/signaling pathways altered via maternal PFAS exposure. Timed-pregnant CD-1 dams were fed a standard chow or 60% kcal high-fat diet. From GD1 until PND20, dams were orally gavaged daily with either 0.5% Tween 20, individual PFOA, PFOS, PFHxS at 1 mg/kg, or a mixture (1 mg/kg each, totaling 3 mg/kg). Livers were collected from PND21 offspring and SWATH-MS pro-teomics was performed. IPA analysis revealed disease and biological function pathways involved in liver damage, xenobiotics, and lipid regulation were modulated by PFAS exposure in the PND21 liver: lipid transport, storage, oxidation, and synthesis, xenobiotic metabolism and transport, liver damage and inflammation, and fatty acid metabolism, oxidation and transport. This indicates the pup liver proteome is altered via maternal exposure and predisposes the pup to metabolic dysfunctions.
2024-05-09 | PXD052106 | Pride