Transcriptomic characters of different pregnancy outcomes in CpG-induced nonobese diabetic mice and wild-type controls
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE69407 | GEO | 2016/09/09
SECONDARY ACCESSION(S): PRJNA285446
REPOSITORIES: GEO
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Project description:The bacterial pathogen Listeria monocytogenes breaches the placental barrier and infects the placental/fetal unit resulting in poor pregnancy outcomes. L. monocytogenes is thought to enter the placenta by infection of trophoblasts at the maternal/fetal interface. Trophoblasts are fetal epithelial cells that delineate the maternal/fetal interface and ensure critical functions by promoting all nutritional and waste exchanges between maternal and fetal bloods and by forming a protective immune barrier. In this work, we report the first transcriptomic analysis of L. monocytogenes-infected trophoblasts by RNA sequencing. Primary human trophoblasts (PHT) and BeWo (fused and non-fused) were infected for 5 h with WT L. monocytogenes and highly purified RNA was extracted from infected and control cells. A 200 ng total RNA sample was used for sequencing on Illumina NovaSeq SP flowcell in paired-end 150 bp format to a read yield between 70-80 million reads. Pathway analysis showed that infection upregulated TLR2-, NOD-like, and cytosolic DNA sensing pathways, as well as downstream pro-inflammatory circuitry (NF-KB, AP-1, IRF4, IRF7) leading to the production of mediators known to elicit the recruitment and activation of maternal leukocytes (IL8, IL6, TNFA, MIP-1). Signature genes associated with poor pregnancy outcomes were also upregulated upon infection. Measuring the release of 54 inflammatory mediators confirmed the transcriptomic data and revealed sustained production of tolerogenic factors (IL-27, IL-10, IL-1RA, TSLP) despite infection. Both the SYN and mononuclear trophoblasts produced cytokines, but surprisingly, some cytokines were predominantly produced by the SYN (IL-8, IL-6) or by non-fused trophoblasts (TNFA). Collectively, our data support that trophoblasts act as placental gatekeepers that limit and detect L. monocytogenes infection resulting in a pro-inflammatory response, which may contribute to the poor pregnancy outcomes if the pathogen persists.
2021-07-15 | GSE175815 | GEO
Project description:To investigate local immune mechanisms of intrauterine fetal demise (IUFD), we used the CBA mouse strain, which naturally has mid-late gestation fetal loss. We performed a Treg adoptive transfer and interrogated both pregnancy outcomes and the impact of systemic maternal Tregs on mucosal immune populations at the maternal-fetal interface. Treg transfer prevented fetal loss and increased an MHC-IIlow population of uterine macrophages. Single-cell RNA-sequencing was utilized to precisely evaluate the impact of systemic Tregs on uterine myeloid populations. A population of C1q+, Trem2+, MHC-IIlow uterine macrophages were increased in Treg-recipient mice. The transcriptional signature of this novel uterine macrophage subtype is enriched in multiple studies of human healthy decidual macrophages, suggesting a conserved role for these macrophages in preventing fetal loss.
2023-10-09 | GSE244616 | GEO
Project description:Tissue factor pathway inhibitor (TFPI) is a prominent regulator of blood coagulation and an intriguing constituent of trophoblast cells situated at the maternal-fetal interface. The actions of TFPI extend beyond controlling hemostasis and directly affect trophoblast cell development. TFPI facilitates the differentiation of rat and human trophoblast stem cells into the invasive trophoblast/extravillous cell lineage and promotes intrauterine trophoblast invasion and trophoblast-guided uterine spiral artery remodeling at the maternal-fetal interface. Thus, TFPI is a conserved regulator of a fundamental event determining the efficacy of the hemochorial placenta.
2021-11-25 | GSE171754 | GEO
Project description:Tissue factor pathway inhibitor (TFPI) is a prominent regulator of blood coagulation and an intriguing constituent of trophoblast cells situated at the maternal-fetal interface. The actions of TFPI extend beyond controlling hemostasis and directly affect trophoblast cell development. TFPI facilitates the differentiation of rat and human trophoblast stem cells into the invasive trophoblast/extravillous cell lineage and promotes intrauterine trophoblast invasion and trophoblast-guided uterine spiral artery remodeling at the maternal-fetal interface. Thus, TFPI is a conserved regulator of a fundamental event determining the efficacy of the hemochorial placenta.
2021-11-25 | GSE171753 | GEO
Project description:Tissue factor pathway inhibitor (TFPI) is a prominent regulator of blood coagulation and an intriguing constituent of trophoblast cells situated at the maternal-fetal interface. The actions of TFPI extend beyond controlling hemostasis and directly affect trophoblast cell development. TFPI facilitates the differentiation of rat and human trophoblast stem cells into the invasive trophoblast/extravillous cell lineage and promotes intrauterine trophoblast invasion and trophoblast-guided uterine spiral artery remodeling at the maternal-fetal interface. Thus, TFPI is a conserved regulator of a fundamental event determining the efficacy of the hemochorial placenta.
2021-11-25 | GSE171223 | GEO
Project description:Intrauterine exposure to disturbed maternal glucose metabolism is associated with adverse consequences for the offspring. Hepatic disorders in affected offspring emerge in early development; thus, detection of disease biomarkers at an early stage may elucidate the underlying mechanisms of maternal hyperglycemia-induced metabolic disease and improve timely diagnosis and treatment strategies. To systematically study the molecular consequences of maternal hyperglycemia, we used data independent acquisition (DIA) proteomics and compared the molecular profiles of liver of three days old wild-type piglets born to a transgenic hyperglycemic pig model with those of wild-type piglets born to normoglycemic mothers.
2023-07-10 | PXD040305 | Pride
Project description:Spleen conventional dendritic cells from NOD mice show a lower overall response to CpG-A compared to B6 cDCs.
2016-02-01 | GSE75883 | GEO
Project description:Background: Chromosomal 16p11.2 deletions and duplications are genomic disorders which are characterized by neurobehavioral abnormalities, obesity, congenital abnormalities and so on. However, the prenatal phenotypes of 16p11.2 copy number variations (CNVs) are still not well described till now. This study aimed to provide an elaborate summary of intrauterine phenotypic features for such genomic disorders. Methods: Twenty prenatal amniotic fluid samples diagnosed with 16p11.2 microdeletions/microduplications were obtained from pregnant women who opted for invasive prenatal testing. Karyotypic analysis and chromosomal microarray analysis (CMA) were performed in parallel. The pregnancy outcomes and health conditions after birth for all cases were followed up. Meanwhile, we made a pooled analysis on the prenatal phenotypes for the published cases carrying 16p11.2 CNVs. Results: 20 fetuses (20/20884, 0.10%) with 16p11.2 CNVs were identified: five 16p11.2 BP2-BP3 deletion, ten 16p11.2 BP4-BP5 deletion and five 16p11.2 BP4-BP5 duplication. Abnormal ultrasound findings were recorded in ten participants with 16p11.2 deletions.Various degrees of intrauterine phenotypic features, ranging from normal to abnormal, were observed. No ultrasound abnormalities were observed for all 16p11.2 duplication cases during the pregnancy period. For 16p11.2 deletions, eleven cases terminated their pregnancies. For 16p11.2 duplications, four cases gave birth to healthy neonates except one was lost to follow up. Conclusions: Diverse prenatal phenotypes were presented in 16p11.2 CNVs, ranging from normal to abnormal. For 16p11.2 BP4-BP5 deletion, the most common structural and non-structural abnormalities were the abnormality of the vertebral column or rib and thickened nuchal translucency, respectively. 16p11.2 BP2-BP3 deletion might be closely associated with fetal growth restriction and single umbilical artery. No representative ultrasound findings for 16p11.2 duplication were observed till now. Considering the variable expressivity and incomplete penetrance of 16p11.2 CNVs, long term follow up after birth should be carried out for these cases. We identified 20 fetuses carrying the 16p11.2 microdeletions and microduplications using chromosomal microarray analysis. And diverse prenatal phenotypes and the critical genes involved in the deleted/duplicated regions were described in this study.
2024-04-29 | GSE265911 | GEO
Project description:We developed two novel sperm epigenetic clocks by applying Super Learner, an ensemble machine learning algorithm, to predict age from sperm EPIC array DNA methylation data via individual CpG sites and differentially methylated regions (DMRs). Overall, our cox model showed that one-year increase in our developed sperm epigenetic age (SEA) was associated with up to 15% reduction in couples time-to-pregnancy (TTP).
2022-07-06 | GSE185445 | GEO
Project description:The objective of this study was to analyze genome-wide differential methylation patterns in maternal leukocyte DNA in early pregnant and non-pregnant states. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform. Transient widespread hypomethylation was found in early pregnancy as compared with the non-pregnant states. Methylation of nine genes was significantly different in early pregnancy compared to both postpartum and nulligravid states (< 10% False Discovery Rate). Early pregnancy may be characterized by widespread hypomethylation compared to non-pregnant states; there is no apparent permanent methylation imprint after a normal-term gestation. Nine potential candidate genes were identified as differentially methylated in early pregnancy and may play a role in the maternal adaptation to pregnancy. This is an age- and body mass index-matched case-control study comparing the methylation patterns of 27,578 cytosine-guanine (CpG) sites in 14,495 genes in maternal leukocyte DNA in early pregnancy (n=14), in the same women postpartum (n=14), and in nulligravid women (n=14) on a BeadChip platform.
2012-10-15 | E-GEOD-37722 | biostudies-arrayexpress