Maternal Oxycodone Treatment Causes Pathophysiological Changes in the Mouse Placenta
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ABSTRACT:
PROVIDER: PRJNA638545 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11973500_1.fastq.gz | Fastqsanger.gz | |||
| SRR11973500_2.fastq.gz | Fastqsanger.gz | |||
| SRR11973501_1.fastq.gz | Fastqsanger.gz | |||
| SRR11973501_2.fastq.gz | Fastqsanger.gz | |||
| SRR11973502_1.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The goals of this study are to examine how maternal exposure to oxycodone affects the global transcriptome and histological structure of the mouse placenta at 12.5 dpc of pregnancy.retinal transcriptome profiling (RNA-seq) to microarray and quantitative reverse transcription polymerase chain reaction (qRT–PCR) methods and to evaluate protocols for optimal high-throughput data analysis Methods: A high throughput RNA sequencing method was used to examine the global transcriptomic changes affected by oxycodone in male and female conceptuses. Histomorphometrics were used to assess the various regions of the placenta, namely the labyrinth, spongiotrophoblast, and parietal trophoblast giant cell (pTGC) region. The open-sourced software, weighted correlation network analysis (WGCNA) was used to link gene expression changes and histological (phenotypic) changes. Results: Using an optimized data analysis workflow, we mapped over 40 million sequence reads per sample to the mouse genome (build grcm38). An average of 95.6% of reads (38.7 million) was mapped with HISAT2 workflow. We identified 12,138 transcripts in the placenta of saline control and oxycodone mice with featureCounts workflow. One hundred eighty-eight transcripts showed differential expression between the OXY male vs. CTL male placenta, with a log2Foldchange ≥1 and p value <0.05. Fifty-eight transcripts showed differential expression between the OXY female vs. CTL female placenta, with a log2Foldchange ≥1 and p value <0.05. Hierarchical clustering of differentially expressed genes uncovered several genes that may contribute to placenta function. Conclusions: Our study represents the first detailed analysis of placental transcriptomes in oxycodone-exposed mice, with biologic replicates, generated by RNA-seq technology. The data analysis workflows reported here should provide a framework for comparative investigations of expression profiles. We conclude that oxycodone exposure changed transcriptome characterization and these changes were associated with placenta histological features.
2020-09-14 | GSE152172 | GEO
Project description:IntroductionPregnant women are increasingly being prescribed and abusing opioid drugs. As the primary communication organ between mother and conceptus, the placenta may be vulnerable to opioid effects but also holds the key to better understanding how these drugs affect long-term offspring health. We hypothesized that maternal treatment with oxycodone (OXY), the primary opioid at the center of the current crisis, deleteriously affects placental structure and gene expression patterns.MethodsFemale mice were treated daily with 5 mg OXY/kg or saline solution (Control, CTL) for two weeks prior to breeding and until placenta were collected at embryonic age 12.5. A portion of the placenta was fixed for histology, and the remainder was frozen for RNA isolation followed by RNAseq.ResultsMaternal OXY treatment reduced parietal trophoblast giant cell (pTGC) area and decreased the maternal blood vessel area within the labyrinth region. OXY exposure affected placental gene expression profiles in a sex dependent manner with female placenta showing up-regulation of many placental enriched genes, including Ceacam11, Ceacam14, Ceacam12, Ceacam13, Prl7b1, Prl2b1, Ctsq, and Tpbpa. In contrast, placenta of OXY exposed males had alteration of many ribosomal proteins. Weighted correlation network analysis revealed that in OXY female vs. CTL female comparison, select modules correlated with OXY-induced placental histological changes. Such associations were lacking in the male OXY vs. CTL male comparison.DiscussionResults suggest OXY exposure alters placental histology. In response to OXY exposure, female placenta responds by upregulating placental enriched transcripts that are either unchanged or downregulated in male placenta. Such changes may shield female offspring from developmental origins of health and disease-based diseases.
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Project description:Transcriptional profiling to map the changes in placental function subsequent to maternal experimental UTI that result in intrauterine growth restriction. One condition experiment: 2 biological replicates of placenta from mice with maternal experimental UTI, 2 biological replicates of placenta from mice with sham UTI.
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Project description:Obese women who develop gestational diabetes show lower adiponectin levels across pregnancy than obese euglycemic women suggesting that obese women with low adiponectin levels have an impaired capacity to handle the metabolic changes during pregnancy. Adiponectin acts on the placenta during pregnancy; this fact allows for the interesting possibility that adiponectin can exert endocrine effects on the developing fetus. The aim was to investigate how adiponectin affects fetal growth, placenta function and metabolic functions during pregnancy. Wild-type (wt) and adiponectin transgenic (APNtg) mice were fed normal chow or a high fat/high sucrose (HF/HS) diet for 8 weeks before mating. Dams and fetuses were dissected at gestational day 18.5. Maternal adiponectin overexpression decreased fetal body weight in dams on normal chow, and even more in dams on HF/HS diet. Pools of two placentas or two livers from one male and one female fetus with the same genotype (wt or APNtg) from the same dam on HF/HS diet were used in proteomic analysis, and a total of five pools per group (wt-wt, wt-APNtg, APNtg-wt, APNtg-APNtg) were included in the liquid chromatography-tandem mass spectrometry (LS-MS/MS) analysis. In total, 7290 proteins were identified in placenta, and 7301 proteins in fetal liver. Next, we analyzed phosphosites, in total,19264 sites were identified in placenta proteins and 15334 sites were identified in fetal liver proteins. We then applied pathway analysis to the total protein and phosphopeptide data using PRISM and Enrichr.
2025-04-23 | PXD025390 | Pride
Project description:Activation of the maternal immune system during pregnancy can fetal development, which can lead to postnatal susceptibility to a wide range of diseases, including cardiovascular, metabolic and psychiatric disorders. During maternal immune activation (MIA), the maternal body must balance its ressources between mounting an immune response and investing resources into continued metabolism and growth : both essential for survival of the fetus and a successful pregnancy. How the placenta responds to MIA over time and how it can protect the fetus is not well understood, and neither are the fetal consequences of MIA. Here, we characterised the response to an induced acute inflammation in maternal lungs over time across maternal and fetal organs, using a combination of omics-methods, imaging and integrative computational analysis. We found that the placenta, unlike other maternal organs, did not react by inducing a typical inflammatory response, but instead initially induced genes associated to strengthen tissue integrity and simultaneously reduced growth to prevent exposure to potential infections. Afterwards, a return to homeostasis was observed, with heightened biosynthesis and expression of endoplasmic reticulum (ER) stress genes. This mechanism likely protects the fetus from inflammation, as we observed no immune response in the fetal liver transcriptome. Instead, we observed metabolic adaptations in the fetus, including a release of docosahexaenoic acid (DHA) Notably, DHA has a crucial function for fetal brain development , and levels of triglyceride and phosphatidylcholine lipids that are necessary for transportation of DHA to the brain were also increased. This metabolic response is likely a combination of the placental MIA response and temporary maternal fasting, caused by MIA-induced fever and lack of nutrient intake. Our study shows, for the first time, the temporal and systemic response to MIA in lungs across maternal and fetal organs.
2024-06-13 | PXD039402 | Pride
Project description:Analyse of gene expression modification after chronic analgesic treatment. The hypothesis tested in the present study was that oxycodone and morphine induced gene expression modification. Results provide important information to understand the analgesic effects of oxycodone as compared to morphine in a neuropathic pain model Total RNA obtained from DRG of neuropathic or control animals after oxycodone or morphine treatment
2014-01-09 | E-GEOD-53897 | biostudies-arrayexpress
Project description:We used sn-RNA-seq to profile the transcriptome of term placenta from two different maternal BMI conditions (maternal obesity: BMI >= 35; lean: 18.5-25).
2025-06-17 | GSE271976 | GEO
Project description:Purpose: Next generation bulk RNA sequencing of a large group (37 individuals) of matched tissues (fetal brain and fetal placenta) from human fetuses collected via elective termination at 72-82 days post conception (d.p.c.), a timeframe that closely matches the embryonic developmental window used in our mouse studies (14.5-16.5) Methods: Human placenta (maternal decidua separated from fetal placenta) and fetal brain tissues were obtained from the NIH-supported Laboratory of Developmental Biology at the University of Washington between the years 1999 and 2010 and used under a protocol approved by the Duke University Institutional Review Board (Pro00014066). Tissue specimens were stored at -80°C until required for RNA or protein extraction. Prior to collection, informed consent was obtained from all individuals undergoing the elective termination. RNA from human tissue was prepared for sequencing using an Illumina TrueSeq RNA Exome kit and sequenced on an Illumina NovaSeq 6000 configured for a S2 flow cell at 50bp PE. Results: PCR for the Y chromosome (SRY) identified 17 male and 20 female fetal tissue sets, with the average age of 78.2 d.p.c. for both sexes. No maternal data were available, so we assessed decidual triglyceride accumulation to use as a proxy for maternal weight, given that women with overweight/obesity exhibit triglyceride accumulation in the placenta. Triglyceride levels trended higher in pregnancies with female fetuses, but there was no significant difference between triglyceride accumulation in decidua associated with male or female pregnancies. Pearson's Correlation of gene expression with maternal triglyceride accumulation from bulk RNA-seq from 16 matched male and 19 matched female brain and placenta samples revealed a strong dimorphic trend in gene expression. In male pregnancies, differentially correlated genes were predominantly over-expressed with increasing maternal weight (i.e. gene expression increased as maternal triglycerides increased); the opposite effect was seen in female pregnancies. In the male brain, only 45 genes significantly correlated with maternal triglyceride accumulation (either positive or negative), whereas 781 genes were significantly correlated in females.
2021-11-18 | GSE188872 | GEO
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:Pregnant women may be prescribed opioid drugs for pain or may abuse these drugs. The placenta may be key to understanding how opioids cause adverse pregnancy outcomes. Maternal oxycodone (OXY) exposure of pregnant mice leads to disturbances in the layer of invasive parietal trophoblast giant cells (pTGC) that forms the interface between the placenta and uterus and is analogous to extravillous trophoblasts of the human placenta. These cells are probably crucial to coordinating the metabolic needs of the conceptus with those of the mother and are also primary participants in the placenta-brain axis. Their large nuclear size, however, has precluded both single cell (sc) and single nucleus (sn) RNA-seq analyses beyond embryonic day (E) 8.5. Here we compared the transcriptomes of placentas from pregnant mice exposed to OXY with unexposed controls at E12.5, with particular emphasis on the pTGC. The non-fluidic Parse snRNA-seq approach permitted characterization of the nuclear transcriptomes of the major placental cell lineages and their presumed progenitors at E12.5. OXY exposure had negligible effect on components of the placental labyrinth, including the two syncytial cell layers, but caused transcriptomic changes consistent with metabolic stress throughout the spongiotrophoblast. Most notably, there was loss of the majority of pTGCs, whose normal gene expression is consistent with elevated energy demand relating to biosynthesis of multiple secretory products, especially hormones, and endoduplication of DNA. This unusual sensitivity of pTGC may put the pregnancy and future health of the offspring at particular risk to OXY exposure.
2024-07-01 | GSE271203 | GEO