Fetal liver programming induced by placental endocrine malfunction
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Mus musculus
SUBMITTER: Russell Hamilton
PROVIDER: E-MTAB-11457 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The placenta regulates maternal-fetal communication, and its defect leads to significant pregnancy complications. The maternal and embryonic circulations are primitively connected in early placentation, but the function of the placenta during this developmentally essential period is relatively unknown. We thus performed a comparative proteomic analysis of the placenta before and after primary placentation and found that the metabolism and transport of lipids were characteristically activated in this period. The placental fatty acid (FA) carriers in specific placental compartments were upregulated according to gestational age, and metabolomic analysis also showed that the placental transport of FAs increased in a time-dependent manner. Further analysis of two mutant mice models with embryonic lethality revealed that lipid-related signatures could reflect the functional state of the placenta. Our findings highlight the importance of the nutrient transport function of the primary placenta in the early gestational period and the role of lipids in embryonic development.
2023-09-06 | PXD026858 | Pride
Project description:<p>Exposure to diabetes in utero is known to increase the offspring's likelihood of developing metabolic disease in adulthood, but the mechanisms involved are unknown. It has been proposed that early exposure to hyperglycemia and elevated insulin levels may lead to malprogramming of the fetus leading to the subsequent development of diabetes and obesity. Epigenetic modifications of the genome including DNA methylation, provide a plausible mechanism that allows for permanent propagation of gene activity states from one generation of cells to the next. </p> <p>The placenta, a fetal tissue easily accessible for study, is a complex organ that is essential in regulating fetal growth. The changes in placental nutrient transport associated with diabetes during pregnancy (DDP) have significant effects on the developing fetus, indicating that the placenta plays a critical role in fetal programming. The aim of our study was to investigate whether exposure to DDP alters genome-wide DNA methylation in the placenta obtained from term pregnancies resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression.</p>
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Project description:Firemaster® 550 (FM 550) is a flame retardant (FR) mixture that has become one of the most commonly used FRs in foam-based furniture and baby products. Human exposure to this commercial mixture, comprised of brominated and organophosphate components, is widespread. We have repeatedly shown that developmental exposure can lead to sex-specific behavioral effects in rats. Accruing evidence of endocrine disruption and potential neurotoxicity have raised concerns regarding the neurodevelopmental effects of FM 550 exposure, but the specific mechanisms of action remains unclear. Additionally, we observed significant, and in some cases sex-specific, accumulation of FM 550 in placental tissue following gestational exposure. Because the placenta is an important source of hormones and neurotransmitters for the developing brain, it may be a critical target of toxicity to consider in the context of developmental neurotoxicity. Using a mixture of targeted and exploratory approaches, the goal of the present study was to identify possible mechanisms of action in the developing forebrain and placenta. Wistar rat dams were orally exposed to FM 550 (0, 300, or 1,000 µg/day;) for 10 days during gestation and placenta and fetal forebrain tissue collected for analysis. In placenta, evidence of endocrine, inflammatory, and neurotransmitter signaling pathway disruption was identified. Notably, 5-HT turnover was reduced in placental tissue and fetal forebrains indicating that 5-HT signaling between the placenta and the embryonic brain may be disrupted. These findings demonstrate that environmental contaminants, like FM 550, have the potential to impact the developing brain by disrupting normal placental functions.
2018-02-28 | GSE108965 | GEO
Project description:<p>Myostatin (gene symbol: Mstn) is an autocrine and paracrine inhibitor of muscle growth. Pregnant mice with genetically reduced levels of myostatin give birth to offspring with greater adult muscle mass and bone biomechanical strength. However, maternal myostatin is not detectable in fetal circulations. Fetal growth is dependent on the maternal environment, and the provisioning of nutrients and growth factors by the placenta. Thus, this study examined the effect of reduced maternal myostatin on maternal and fetal serum metabolomes, as well as the placental metabolome. Fetal and maternal serum metabolomes were highly distinct, which is consistent with the role of the placenta in creating a specific fetal nutrient environment. There was no effect from myostatin on maternal glucose tolerance or fasting insulin. In comparisons between pregnant control and Mstn+/− mice, there were more significantly different metabolite concentrations in fetal serum, at 50, than in the mother’s serum at 33, confirming the effect of maternal myostatin reduction on the fetal metabolic milieu. Polyamines, lysophospholipids, fatty acid oxidation, and vitamin C, in fetal serum, were all affected by maternal myostatin reduction.</p>
2023-06-08 | MTBLS3345 | MetaboLights
Project description:Protein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection. 2x2 factorial.
2015-09-09 | E-GEOD-57115 | biostudies-arrayexpress
Project description:Context: An increase in maternal insulin resistance (IR) during pregnancy is essential for normal fetal growth. The mechanisms underlying this metabolic adaptation to pregnancy are poorly understood. Placenta factors are believed to instigate and maintain these metabolic changes, as IR decreases shortly after delivery. Methylation of placental gene loci that are common targets for miRNAs, are associated with maternal IR. Objective: We hypothesized that placental miRNAs targeting methylated loci are associated with maternal IR during late pregnancy. Methods: Placental miRNA expression was measured via small RNA-sequencing in a subset of 40 placentas selected by maternal pre-gravid BMI and neonatal adiposity. Results: Median maternal age was 27.5 years, with a median pre-pregnancy BMI of 24.7 kg/m2, and median HOMA-IR of 2.9. Among the five selected miRNA, near delivery maternal HOMA-IR correlated with the placental expression of miRNA-371b-3p (r=0.25; p=0.008) and miRNA-3940-3p (r=0.32; p=0.0004) across the 132 individuals. After adjustment for confounding variables, placental miRNA-3940-3p expression remained significantly associated with HOMA-IR (β=0.16; p=0.03). Conclusion: Placental miRNA may have an autocrine or paracrine effect - regulating placental genes which play a role in modulating maternal IR.
2023-03-01 | GSE169523 | GEO
Project description:Maternal obesity in mice negatively affects placental functionand maternal and fetal liver function. We performed a global proteomic analysis using a liquid-chromatography/mass-spectrometry system to investigate total and phosphorylated proteins in the placenta and fetal liver in a mouse model that combines maternal obesity with maternal androgen excess to identify changes in molecular pathways that might promote diseases in adulthood.
2019-01-24 | PXD011722 | Pride
Project description:There is a growing need to understand the potential neurotoxicity of organophosphate ester flame retardants (OPFRs) and plasticizers because use and, consequently, human exposure, is rapidly expanding. We have previously shown in rats that developmental exposure to the commercial FR mixture Firemaster® 550 (FM 550), which contains OPFRs, results in sex-specific behavioral effects, and identified the placenta as a potential target of toxicity. The placenta is a critical coordinator of fetal growth and neurodevelopment, and a source of neurotransmitters (NTs) for the developing brain. We have shown in rats and humans that FRs accumulate in placental tissue, and induce functional changes, including altered neurotransmitter (NT) production. Here we sought to establish if OPFRs (triphenyl phosphate, TPHP, and a mixture of isopropylated triarylphosphate isomers, ITPs) alter placental function and fetal forebrain development, with disruption of tryptophan (Trp) metabolism as a primary pathway of interest. Wistar rat dams were orally exposed to OPFRs (0, 500, 1,000, or 2,000 μg/day) or a serotonin (5-HT) agonist (5-MT) for 14 days during gestation and placenta and fetal forebrain tissues collected for analysis by transcriptomics and metabolomics. Relative abundance of genes responsible for the transport and synthesis of placental 5-HT were disrupted, and multiple neuroactive metabolites in the 5-HT and kynurenine (Kyn) metabolic pathways were upregulated. Additionally, 5-HTergic projections were significantly longer in the fetal forebrains of exposed males. These findings suggest that OPFRs have the potential to impact the 5-HTergic system in the fetal forebrain by disrupting placental Trp metabolism.
2020-04-08 | GSE148266 | GEO
Project description:Protein deficiency and intestinal parasite infection during pregnancy impair fetal growth through passage of signals from the maternal environment which signal impairment of fetal growth. The placenta is an important regulator of the transfer of these signals through differential expression of key placental genes. We used microarrays to examine placental gene expression responses to maternal protein deficiency (6% vs. 24% protein) and Heligmosomoides bakeri infection.
2015-09-09 | GSE57115 | GEO
Project description:The mammalian placenta is both the physical interface between mother and fetus, and the source of endocrine signals that target the maternal hypothalamus, priming females for parturition, lactation and motherhood. Despite the importance of this connection, the effects of altered placental signaling on the maternal brain are understudied. Here, we show that placental dysfunction alters gene expression in the maternal brain, with the potential to affect maternal behavior. Using a cross between the house mouse and the Algerian mouse in which hybrid placental development is abnormal, we sequenced late gestation placental and maternal medial preoptic area transcriptomes and quantified differential expression and placenta-maternal brain co-expression between normal and hybrid pregnancies. The expression of Fmn1, Drd3, Caln1 and Ctsr was significantly altered in the brains of females exposed to hybrid placentas. Most strikingly, expression patterns of placenta-specific gene families and Drd3 in the brains of house mouse females carrying hybrid litters matched those of female Algerian mice, the paternal species in the cross. Our results indicate that the paternally-derived placental genome can influence the expression of maternal-fetal communication genes, including placental hormones, suggesting an effect of the offspring's father on the mother’s brain.
2019-12-31 | GSE126469 | GEO