Evolved Levels of Placental Invasion in Human and Bovine Endometrial Stroma
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ABSTRACT:
PROVIDER: PRJNA562073 | ENA |
REPOSITORIES: ENA
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Project description:Among mammals, the extent of placental invasion is correlated with vulnerability to malignancy. Animals with more invasive placentation (e.g. humans) are more vulnerable to malignancy, whereas animals with a non-invasive placenta (e.g. ruminants) are less likely to develop malignant cancer. To explain this correlation,we propose the hypothesis of Evolved Levels ofInvasibility (ELI) positing that the permissiveness of stromal tissue to invasion is a unitary character affecting both placental and cancer invasion. We provide evidence for this hypothesis by contrasting invasion of human and bovine cancer and placental cells into a lawn of stromal cells from different species. We find that both bovine endometrial andskin fibroblasts are more resistant to invasion of placental and cancer cells than their human counterparts. Gene expression profiling identified genes with high expression in human but not bovine fibroblasts. Knocking down of a subset of them in human fibroblasts leads to significantly stronger resistance to cancer cell invasion. Comparative analysis of gene expression among mammals suggests that humans evolved higher vulnerability to malignancy than the eutherian ancestor, possibly as a correlate of more invasive placentation, and boroeutherians evolved to decrease stromal invasibility. Identifying the evolutionary determinants of stromal invasibility can provide significant insights to developrational anti-metastatic therapeutics.
2019-10-24 | GSE136299 | GEO
Project description:The placenta is an understudied organ that has a critical role in mammalian development. In early placental development, the essential process of trophoblast invasion establishes adequate blood flow between mother and fetus. Despite its importance, little is known about the genomic regions responsible for regulating trophoblast invasion. In order to identify enhancers that are important for regulating the process, we carried out ChIP-Seq for an enhancer-associated mark at two time points during early placental development. Combining these data with RNA-Seq data and protein interaction data allowed us to construct a gene-enhancer network describing trophoblast invasion.
2015-12-01 | GSE65808 | GEO
Project description:The placenta is an understudied organ that has a critical role in mammalian development. In early placental development, the essential process of trophoblast invasion establishes adequate blood flow between mother and fetus. Despite its importance, little is known about the genomic regions responsible for regulating trophoblast invasion. In order to identify enhancers that are important for regulating the process, we carried out ChIP-Seq for an enhancer-associated mark at two time points during early placental development. Combining these data with RNA-Seq data and protein interaction data allowed us to construct a gene-enhancer network describing trophoblast invasion.
2015-12-01 | GSE65807 | GEO
Project description:Placental Accreta Spectrum: Upregulated Cytotrophoblast DOCK4 Contributes to Over Invasion
| PRJNA561109 | ENA
Project description:In humans, a subset of placental cytotrophoblasts (CTBs) invades the uterus and its vasculature, anchoring the pregnancy and ensuring adequate blood flow to the fetus. Appropriate depth is critical. Shallow invasion increases the risk of pregnancy complications, e.g., severe preeclampsia. Overly deep invasion, the hallmark of placenta accreta spectrum (PAS), increases the risk of pre-term delivery, hemorrhage and death. Previously a rare condition, the incidence of PAS has increased to 1:731 pregnancies, likely due to the rise in uterine surgeries (e.g., Cesarean sections). CTBs track along the scars deep into the myometrium and beyond. Here we compared the global gene expression patterns of CTBs from PAS cases to gestational age-matched control cells that invaded to the normal depth from preterm birth (PTB) deliveries. The mRNA encoding the guanine nucleotide exchange factor, DOCK4, mutations of which promote cancer cell invasion and angiogenesis, was the most highly differentially expressed molecule in PAS samples. Over-expression of DOCK4 increased CTB invasiveness, consistent with the PAS phenotype. Also, this analysis identified other genes with significantly altered expression in this disorder, potential biomarkers. These data suggest that CTBs from PAS cases up regulate a cancer-like pro-invasion mechanism, suggesting molecular as well as phenotypic similarities in the two pathologies.
2019-09-30 | GSE136048 | GEO
Project description:In this study, we identify SYDE1 as a novel GCM1 target gene. We demonstrate that SYDE1 promotes placental cell migration and invasion and that the GCM1-SYDE1 axis is crucial for placental development. Importantly, retarded placental and fetal growth with defective spongiotrophoblast layer, compromised vasculogenesis, and abnormal maternal-trophoblast interface are noted in the Syde1 homozygous knockout (KO) placenta. Along this line, decreased SYDE1 expression is observed in human IUGR placentas. We further demonstrated that components of the renin-angiotensin system (RAS) and Syde2 are differentially expressed in Syde1-KO placenta, which might contribute to normal neonatal delivery in Syde1-KO mothers
2016-10-18 | GSE81468 | GEO
Project description: Not available
| S-EPMC8591203 | biostudies-literature
Project description:The whole-gene expression profile of 24 endometrial stroma sarcol was used to identify genes that were deregulated in the tumors genome.
2016-07-01 | GSE73361 | GEO
Project description:The whole-gene expression profile of 24 endometrial stroma sarcol was used to identify genes that were deregulated in the tumors genome. The analysis was performed comparing the high-grade to the low-grade tumors.
2016-07-01 | E-GEOD-73361 | biostudies-arrayexpress
Project description:Fibrosis are known as one of the characteristic pathological findings of placenta in preeclampsia (PE). The mechanism underlying tissue injury when placental stroma is exposed to hypoxia and inflammatory stimulation is unclear. We focused on the relationship between pathogenesis of PE and placental fibrosis, and investigated the changes of fibrosis related factors (FRFs) in placental stroma. The mRNA levels of fibrosis related factors in PE were higher than those in normal pregnancy (NP). Those under hypoxia and by TGF-β stimulation were more prominent in PE compared with NP. The contraction rate of PE had significantly higher than that of NP. The significant elevation of plasma level of TGF-β in PE was indicated compared with those in NP.
2017-05-18 | GSE99007 | GEO