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F1 Interspecies Hybrid Analysis Reveals Parent-Of-Origin Bias in the Mouse Placenta

ABSTRACT: To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta. 3'-end Sequencing for Expression Quantification (3SEQ) and SNP Analysis to observe parent-of-origin bias in 28 placental samples at two time points and 2 yolk sac samples

ORGANISM(S): Mus musculus

SUBMITTER: Elizabeth Finn

PROVIDER: E-GEOD-42671 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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F1 Interspecies Hybrid Analysis Reveals Parent-Of-Origin Bias in the Mouse Placenta

Project description:To investigate the epigenetic landscape at the interface between mother and fetus, we provide a comprehensive analysis of parent of origin bias in the placenta. Using F1 interspecies hybrids, we sequenced RNA from 23 individual midgestation placentas, five late stage placentas, and two yolk sac samples and then used SNPs to determine whether transcripts were preferentially generated from the maternal or paternal allele. In the placenta, we find 103 genes that show significant and reproducible parent-of-origin bias, of which 78 are novel candidates. Most (96%) show a strong maternal bias which, using multiple models, we demonstrate is not due to maternal decidual contamination. Analysis of the X chromosome also reveals paternal expression of Xist and several genes that escape inactivation, most significantly Rps4x, Fhl1, and Slc38a5. Finally, sequencing individual placentas allowed us to reveal notable expression similarity between littermates. In all, we observe a striking preference for maternal transcription in the midgestation mouse placenta and a dynamic imprinting landscape in extraembryonic tissues, reflecting the complex nature of epigenetic pathways in the placenta.

2014-02-28 | GSE42671 | GEO

Maternal iron deficiency modulates placental transcriptome and proteome in mid-gestation of mouse pregnancy

Project description:Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental response to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. Objectives: Our primary aim was to identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. Methods: We used a real-time PCR based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n=3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron adequate mice at E12.5 (n=8 dams/diet). Results: In female placentas, six genes including transferrin receptor (Tfrc) and solute carrier family 11 member 2 were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. Proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron responsive element (IRE) containing mRNAs were altered in abundance; ferritin and ferroportin 1 decreased while TFRC increased in ID placenta. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.

2021-03-12 | PXD023454 | Pride

Proteomic profiles of ZIKV-positive placentas of fetuses with microcephaly

Project description:Here we use a proteomic approach to study the role of the placenta in ZIKV-induced microcephaly and the mechanisms of ZIKV to cross the placental barrier. Samples were separated into three groups: an uninfected control group (ZIKV-CZS-), a group of placentas infected by ZIKV with normal neonates (ZIKV+CZS-), and a group of placentas infected by ZIKV that developed microcephaly in newborns (ZIKV+CZS+). Zika virus causes DNA damage and impairs gene expression and mRNA translation during infection of the placenta. Processes related to viral transcytosis, like endocytosis, autophagy and disruption of actin filament were also observed in CZS-infected placentas, which could lead to a higher virus infiltration. Unncontrolled maternal immune response as well as greater expression of cellular adhesion proteins in the decidua could lead to a disruption of tolerance during pregnancy and induction of neurological malformation of the neonates

2024-07-02 | PXD023777 | Pride

Chromosome-wide profiling of X-inactivation status and epigenetic regulation in opossum fetal brain and placenta

Project description:Evidence from a few genes of diverse species suggests that marsupial X-chromosome inactivation (XCI) is characterized by exclusive, but leaky, inactivation of the paternally derived X chromosome. To comprehensively study the mechanism of marsupial XCI, we profiled parent-of-origin-specific-allele expression, DNA methylation, and histone modifications in opossum fetal brain and extra-embryonic membranes. The majority (152/176) of X-linked genes exhibited paternally imprinted expression with nearly 100% maternal allele expression, whereas 24 loci (14%) escaped inactivation showing varying levels of biallelic expression. In addition to regulation by the non-coding RSX transcript, strong depletion of H3K27me3 at escaper gene loci indicates that histone states also influence opossum XCI. Notably, the opossum does not show an association between X-linked gene expression and promoter DNA methylation. Our study provides the first comprehensive catalogue of parent-of-origin expression status for X-linked genes in a marsupial and sheds light on the regulation and evolution of imprinted XCI in mammals. Profiling of expression level and allele-specific expression ratios in embryonic day 13 opossum (Monodelphis domestica) fetal brain and extra-embyonic membranes by Illumina RNA-seq

2013-09-23 | E-GEOD-45211 | biostudies-arrayexpress

Immunological Sexual Dimorphism in Placenta and Its Response to Benzene Exposure

Project description:There is increasing concern regarding the adverse effects of air pollution on human health, and benzene is a major toxic compound in air pollution. Maternal benzene exposure has been associated with reproductive complications, such as preterm birth, low birth weight, and immunological and neurological complications in the offspring. However, it is poorly understood how benzene induces these complications. Our objective was to establish a full body inhalation mouse model for maternal benzene exposure that mimics clinical phenotypes observed in human populations, and characterize the maternal immune activation and placental response in our model. Here, we report that maternal immune activation triggered by benzene exposure during pregnancy leads to increased resorptions, abnormal placenta development and low birth weight of fetus. More importantly, there is a sexual dimorphic response to benzene exposure in female and male placentas. In the male placenta, the transcriptome changes reveal a more immunologically relevant profile, while females have a metabolically related profile. Furthermore, we discover the sexual dimorphic response could be a consequence of the sexual dimorphism of placenta at baseline, which indicates the significant difference between sexes in terms of the immunological processes in the placenta, both in human and mouse. Therefore, our findings established a benzene exposure mouse model and indicated the sexual dimorphism of placenta, which provides valuable reference for the future pregnancy studies.

2023-07-20 | PXD035085 | Pride

Transcription profiling of mouse placenta at different developmental time points

Project description:We used full genome microarrays to profile the full lifetime of the mouse placenta from embryonic day 8.5 (e8.5), at the time of chorioallantoic fusion, until postnatal day 0 (P0). For these samples, at each stage the fetal placenta and maternal decidual tissues were dissected and profiled separately (See series 1). For this experiment (Series 2), placental and decidual timecourse samples were normalized and modeled with two undissected (including placental and decidual tissue) e17 placentas to allow for scaling of values for comparison to the undissected placenta samples used in the publicly available mouse GeneAtlas dataset Experiment Overall Design: Mouse placentas were obtained from timed pregnant female mice at each timepoint, and fetal tissues were used to confirm embryo staging. For all dissected samples, fetal placenta and maternal decidual tissues were dissected and pooled separately for each litter prior to RNA extraction and hybridization on Affymetrix microarrays.

2008-06-11 | E-GEOD-11222 | biostudies-arrayexpress

microRNA sequencing of human placentae and matched maternal plasma from 6-23 weeks of gestation

Project description:microRNAs are increasingly seen as important regulators of placental development and opportunistic biomarker targets. We generated miRNA profiles using 96 placentas from presumed normal pregnancies, across early gestation, in combination with matched profiles from maternal plasma. We identified 637 miRNAs with expression in 86 samples (after removing poor quality samples), showing a clear gestational age gradient and identified 374 differentially expressed (DE) miRNAs across a gestational cut-off of 6-10 weeks’ and 11-23 weeks’. We see a clear gestational age group bias in miRNA clusters C19MC, C14MC, miR-17~92 and paralogs, regions that also include many DE miRNAs. Proportional change in expression of placenta-specific miRNA clusters was reflected in maternal plasma, with C19MC miRNAs miR-516b-5p and 517a-3p showing potential as a biomarkers. Chorionic villous samples across early gestation display differential miRNA profiles, particularly in the expression of highly placenta-specific miRNA clusters, and at the presumed introduction of oxygenated maternal blood into the placenta. Data presented here comprise a clinically important reference set for studying early placenta development and enabling development of minimally invasive methods for monitoring placental health.

2021-12-23 | GSE151362 | GEO

Transcription profiling of mouse developing placenta, with placental and decidual tissues profiled separately

2008-06-11 | E-GEOD-11220 | biostudies-arrayexpress

Identification of differentially methylated regions between placentas and maternal blood cells on chromosome 18

Project description:Comparison of DNA methylation levels of chromosome 18 between placentas and blood cells of pregnant women Extracted DNA from 5 cases of placental tissues and 5 cases of maternal blood cell was subjected to MeDIP (methylated DNA immunoprecipitation) and hybridized to Affymetrix GeneChip® Human Tiling 2.0R Array sets. A control without immunoprecipitation (IP) was also processed in parallel with the immunoprecipitated DNA samples. The results were validated with bisulfite sequencing and mass spectrometry-based analysis

2010-12-22 | E-GEOD-22837 | biostudies-arrayexpress

Profiling of differential allelic expression in mouse placenta from reciprocal crosses

Project description:Many questions about the regulation, functional specialization, computational prediction, and evolution of genomic imprinting would be better addressed by having an exhaustive genome-wide catalog of genes that display parent-of-origin differential expression. As a first-pass scan for novel imprinted genes, we performed mRNA-seq experiments on E17.5 mouse placenta cDNA samples from reciprocal cross F1 progeny of AKR and PWD mouse strains, and quantified the allele-specific expression and the degree of parent-of-origin effect transcriptome-wide. We confirmed the imprinting status of 23 known imprinted genes in the placenta, and found that 12 genes reported previously to be imprinted in other tissues are also imprinted in mouse placenta. Through a well-replicated design using an orthogonal technology, we verified five novel imprinted genes that are not known to be imprinted in mouse. It appears that most of the strongly imprinted genes have already been identified, at least in the placenta, and that evidence supports perhaps 100 additional weakly imprinted genes. Despite previous appearance that the placenta tends to display an excess of maternally-expressed imprinted genes, when the full set of genes is uniformly scored as in this study, this maternal bias disappeared. Examine allelic expression in E17.5 placenta tissues from two individual samples, one from each of the two reciprocal crosses.

2011-06-15 | E-GEOD-29690 | biostudies-arrayexpress

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