Decidual stromal cell response to paracrine signals from the trophoblast
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE5809 | GEO | 2006/09/18
SECONDARY ACCESSION(S): PRJNA97187
REPOSITORIES: GEO
Similar Datasets
Project description:During the invasive phase of implantation, trophoblasts and maternal decidual stromal cells secrete products that regulate trophoblast differentiation and migration into the maternal endometrium. Paracrine interactions between the extravillous trophoblast and the maternal decidua are important for successful embryonic implantation, including establishing the placental vasculature, anchoring the placenta to the uterine wall, and promoting immuno-acceptance of the fetal allograph. Global cross-talk between the trophoblast and the decidua has not been elucidated to date, and the current study used a functional genomics approach to investigate these paracrine interactions. Human endometrial stromal cells were decidualized with progesterone and were further treated with conditioned media (CM) from human trophoblasts (TCM) or, as a control, with conditioned media (CCM) from non-decidualized stromal cells for 0, 3 and 12 hr. Total RNA was isolated and processed for analysis on whole genome, high density oligonucleotide arrays, containing 54,600 genes. Our data demonstrate a significant induction of pro-inflammatory cytokines and chemokines, as well as angiogenic/static factors in decidualized endometrial stromal cells in response to trophoblast-secreted products. The data suggest that the trophoblast acts to alter the local immune environment of the decidua to facilitate the process of implantation and assure an enriched cytokine/chemokine environment, while limiting mitotic activity of the stromal cells during the invasive phase of implantation.
2007-11-02 | E-GEOD-5809 | biostudies-arrayexpress
Project description:Trophoblast Invasion is a complex mechanism that involves several genes and processes that are exquisitely regulated by the mother. Functional genomics has shown that immunomodulatory and proliferation are two essential key processes involved. Adult virgin B6CBA F1/J female mice were mated with CD1 fertile males to induce pregnancy (day 0=vaginal plug). Mice were sacrificed by cervical dislocation. Implantation and inter-implantation sites were divided by sharp dissection 6.5 days post-coitum (dpc) (n=3 mice). Uterine segments included uterine myometrium, stroma, and epithelium. Inter-implantation decidua (ID) were collected and Implantation sites also were divided by sharp dissection to separate extra-embryonic tissue (ET) from surrounding decidua (SD). From the embryo, only the invasive trophoblast formed by the ectoplacental cone was studied too.
2014-06-02 | E-GEOD-46732 | biostudies-arrayexpress
Project description:Embryos secrete preimplantation factor (PIF), a peptide present in maternal circulation during viable pregnancy. We compared downstream synthetic PIF effect on gene expression in non-pregnant Human Endometrial Stromal Cell (HESC) and First Trimester Decidual cell (FTDC) culture to mimic the maternal intrauterine environment during embryo implantation and trophoblast invasion.
2013-06-21 | GSE46326 | GEO
Project description:Embryos secrete preimplantation factor (PIF), a peptide present in maternal circulation during viable pregnancy. We compared downstream synthetic PIF effect on gene expression in non-pregnant Human Endometrial Stromal Cell (HESC) and First Trimester Decidual cell (FTDC) culture to mimic the maternal intrauterine environment during embryo implantation and trophoblast invasion. Cells were cultured in triplicate with and without synthetic PIF for 24 hours. Cultured cells were then pooled for chip analysis. Altered gene expression relative to controls was assessed by Affymetrix microarray
2013-06-21 | E-GEOD-46326 | biostudies-arrayexpress
Project description:Maternal-embryonic interactions play a critical role in successful pregnancy, with particular emphasis on the decidual-trophoblast interaction, which have been long recognized to exert a paracrine influence through the trophoblast cells on the progression of decidualization and the function of decidual cells. Despite this knowledge, the full extent of the embryo's impact on the decidua remains largely unexplored. To investigate the influence of embryonic signals on the maternal decidua, we utilized Prl3d1Cre/Cre mice mated with R26DTA/DTA mice, resulting in the generation of Prl3d1Cre/+, R26DTA/+ conceptus. In these conceptuses, the primary trophoblast giant cells (pTGCs) were selectively ablated by diphtheria toxin A (DTA). The pTGCs are the key embryonic cells that directly interact with the maternal decidua. Following the ablation of pTGCs, we observed impaired decidualization, as indicated by altered expression of genes related to decidualization or decidual function, such as Prl8a2, Wnt4, Bmp2, Alpl, and Hsd11b2, as well as a reduction in the interferon response in the decidua on day 6.5 of early pregnancy. Additionally, we found significant downregulation of numerous lipid-related biological effects in both deciduae on day 6.5 and day 8 of early pregnancy. These findings shed light on the complex interactions between the maternal and embryonic components during early pregnancy and underscore the importance of embryonic-derived influences on decidual lipid metabolism.
2024-11-30 | GSE240086 | GEO
Project description:Placenta development involves complex molecular and cellular interactions between the maternal endometrium and the developing embryo, however, it is not clear what are the precise mechanisms regulating this maternal-fetal crosstalk. Using genetic and cell biological approaches, we have demonstrated that Ras-related C3 botulinum toxin substrate 1 (Rac1), a maternal factor expressed in decidual cells and is markedly elevated in mouse decidua on days 7 and 8 of gestation, regulates the secretory pathways that mediate stromal-endothelial and stromal-trophoblast crosstalk within a narrow temporal window during placenta development. Our study revealed that ablation of Rac1 did not affect the formation of the decidua but led to fetal loss in mid gestation accompanied by extensive hemorrhage. To gain insights into the molecular pathways affected by the loss of Rac1, we performed gene expression profiling which revealed that RAC1 signaling regulates the expression of genes involved in angiogenesis and vesicle trafficking. Consequently, the Rac1-null decidual cells exhibited impaired secretory functions that led to poor vascularization of the uterus and abnormal trophoblast expansion and placentation.
2017-02-09 | GSE70446 | GEO
Project description:The etiology of fetal growth restriction (FGR) is multifactorial, although many cases often involve placental insufficiency. Placental insufficiency is associated with inadequate trophoblast invasion that results in an environment with high resistance to blood flow, decreased availability of nutrients to the placenta, and increased hypoxia. Despite accumulating knowledge linking inadequate trophoblast invasion with placental insufficiency and FGR, current treatment options are limited to iatrogenic delivery, usually preterm. We have developed a non-viral, polymer-based nanoparticle that facilitates transient human insulin-like 1 growth factor (hIGF1) gene delivery specifically to placental trophoblast. Using the established guinea pig maternal nutrient restriction (MNR) model of placental insufficiency and FGR, the aim of the study was to identify novel pathways in the sub-placenta/decidua that will provide insight into the underlying mechanism driving FGR, and may be corrected with hIGF1 nanoparticle treatment. Pregnant guinea pig dams underwent ultrasound-guided sham or hIGF1 nanoparticle treatment at mid-pregnancy, and sub-placenta/decidua tissue was collected 5 days later. Transcriptome analysis was performed using RNA Sequencing on the Illumina platform. Histological assessment of the sub-placenta/decidua demonstrated fewer maternal spiral arteries lined by trophoblast in the MNR sub-placenta/decidua which was associated with downregulation of genes involved in epithelium development and the regulation of cell migration. hIGF1 nanoparticle treatment results in marked changes to transporter activity in the MNR + hIGF1 sub-placenta/decidua when compared to sham MNR. Under normal growth conditions however, hIGF1 nanoparticle treatment in Control + hIGF1 sub-placenta/decidua was associated with downregulation of kinase signaling and increased proteolysis indicative of homeostasis. Overall, this study identified changes to the sub-placenta/decidua transcriptome that likely result in inadequate trophoblast invasion and that contribute to placental insufficiency. Additionally, this study has increased our understanding of pathways that hIGF1 nanoparticle treatment acts on in order to restore or maintain appropriate placenta function.
2025-03-26 | GSE269098 | GEO
Project description:Epidemiological studies suggest that maternal exposures to environmental chemicals may be linked to spontaneous preterm birth. Mechanistic studies are needed to provide support to these hypotheses; however, existing in vitro models do not replicate the human feto-maternal barriers beyond placenta. The recently developed four-cell (human immortalized maternal decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cells) Feto-Maternal interface Organ-On-Chip (FMi-OOC) enables studies of chemical effects on the decidua, chorion and amnion, maternal and fetal tissues that are critically important for maintaining full-term pregnancy. We tested four environmental compounds that have been associated with preterm birth – dichlorodiphenyltrichloroethane (DDT-o,p’), bisphenol A (BPA), 2,2'4,4'-tetrabromodiphenyl ether (PBDE-47), and perfluorooctanoic acid (PFOA). First, concentration-response effects of these chemicals were tested on maternal decidua cells in 96-well plates. Then, experiments were performed in FMi-OOC containing four fetal-maternal cell types arranged into four concentric chambers, mimicking the in utero cell topology. Compounds were added to the maternal (i.e., decidua) chambers, and chemical propagation, cell viability and proinflammatory cytokines (IL-6, IL-8, GM-CSF, TNF-α) were measured in decidua, chorion trophoblast, amnion mesenchymal, and amnion epithelial cells for up to 72 hrs. Minimal propagation of test compounds to fetal chambers was observed and tested concentrations were non-cytotoxic. Treatment-associated increase in cytokine production was observed for all compounds, with PFOA and BPA showing the strongest effects and amnion epithelial cells being the most responsive. We demonstrate how the multi-cellular FMi-OOC model can be used to study paracrine signaling in complex human tissues such as fetal-maternal interface. In addition, these studies provide mechanistic support for the plausibility of the epidemiological associations between maternal exposures to tested compounds and preterm birth. We show that upon maternal exposure, albeit at concentrations exceeding reported human blood levels by 1 to 2 orders of magnitude, fetal membranes attain a pro-inflammatory state, a potential trigger for preterm birth.
2025-07-28 | GSE295995 | GEO
Project description:Abstract Background During equine implantation, two trophoblast subpopulations are distinguished: the invasive (chorionic girdle) and non-invasive (allantochorion). The invasive chorionic girdle is believed to interact with the maternal immune system and contribute to embryo attachment to the endometrium. However, the mechanism regulating attachment and immune tolerance to these two distinct trophoblast subpopulations remain incompletely understood. The present study aimed to investigate the regulation of gene expression and the biological processes involved in trophoblast attachment, development and maintenance of immune tolerance by comparing the transcriptomes and methylomes of the allantochorion and chorionic girdle trophoblast before and after implantation, that is, between days 33 and 42 of gestation. Results Irrespective of gestational day, allantochorion (N=4) was enriched in TGFB and its receptors TGFBR1 and TGFBR2. Across implantation, expression of regulatory macrophage markers, as IL33, IL4|1, PLG-RKT, or CD163, also increased in that membrane in addition to TFEB and SERPINE1. Invasive chorionic girdle (CG33, N=4) had higher, than the non-invasive allantochorion (ALC33, N=4), expression of NLRC5, a transcriptional regulator of MHC I, and expression of that factor further decreased in allantochorion from gestational day 33 to 42. Furthermore, B2M, which encodes the MHC I light chain, was hypermethylated in the allantochorion. Some genes were differentially methylated and expressed between the two trophoblasts (CAVIN1, LHB, INSR) or beginning and end of implantation (IFNGR1, CD177). Analysis of GOterms and canonical pathways showed that both differentially expressed and methylated genes were involved in critical for implantation processes and pathways as these including cell movement and adhesion, TGFB signaling, fibrosis, wound healing, or leukocyte extravasation. Conclusions Allantochorion may contribute to the formation of the attachment with the endometrium and maintenance of maternal tolerance. Expression of IL33, IL4|1 or CD163 suggests involvement of regulatory macrophages in the implantation. TFEB might be involved in the support of allantochorion steroidogenic functions and maturation. Spatial-temporal differential methylation of genes expressed by the chorionic girdle and allantochorion may contribute to the control of trophoblast invasion and its attachment to endometrium. Finally, methylation of B2M and differential expression of NLRC5, are involved in the control of MHC I expression on equine trophoblasts during implantation. Background: During equine implantation, two distinct trophoblast subpopulations are identified: the invasive chorionic girdle (CG) and the non-invasive allantochorion. The invasive CG is believed to modulate the maternal immune response and facilitates embryo attachment to the endometrium, while the allantochorion contributes to placental development without breaching the endometrium. However, the mechanisms underlying differential adhesion and immune modulation by these two lineages remains poorly understood. This study aimed to investigate the regulation of biological processes underlying trophoblast attachment, development and maintenance of immune tolerance by comparing the transcriptomes and methylomes of CG and allantochorion trophoblasts before and after implantation, that is, between gestational days 33 and 42. Results: Irrespective of gestational day, allantochorion (n=4) was enriched in TGFB and its receptors TGFBR1 and TGFBR2. Across the implantation window, expression of regulatory macrophage markers such as IL33, IL4|1, PLG-RKT, and CD163 increased in the allantochorion, along with upregulation of TFEB and SERPINE1. The invasive GC (CG33, n=4) showed higher expression of NLRC5, a transcriptional regulator of MHC I, compared to the non-invasive allantochorion (ALC33, n=4). Notably, NLRC5 expression declined in the allantochorion from day 33 to 42. Furthermore, B2M, which encodes the MHC I light chain, was hypermethylated in the allantochorion. Several genes, including CAVIN1, LHB, and INSR, were both differentially expressed and methylated between the two trophoblast types, while others, such as IFNGR1, CD177, showed differential regulation across the implantation window. Gene Ontology and pathway analyses revealed that differentially expressed and methylated genes were enriched in biological processes and pathways critical for implantation, including cell migration and adhesion, TGFB signaling, fibrosis, wound healing, and leukocyte extravasation.Conclusions: The allantochorion plays an active role in establishing the attachment to the endometrium and sustaining maternal immune tolerance during implantation. The upregulation of IL33, IL4|1, and CD163 suggests the that the allantochorion may promote the recruitment or polarization of macrophages toward a regulatory phenotype, thereby modulating the local immune environment. TFEB may contribute to the steroidogenic activity and functional maturation of the allantochorion. Spatial and temporal differences in gene methylation between CG and allantochorion suggest involvement of epigenetic regulation in trophoblast invasion and attachment to the endometrium. Finally, combined B2M hypermethylation and differential expression of NLRC5 point to epigenetic and transcriptional control of MHC I expression in the equine trophoblasts during implantation.
2025-08-05 | GSE303997 | GEO
Project description:Receptors of the KIR family on maternal Natural Killer cells in the decidua are believed to bind to Ligands such as HLA-C on trophoblast cells invading into the decidua from the placenta during early pregnancy. The resulting responses regulate the extent of trophoblast invasion. Genetic studies have implicated two members of the KIR family in particular as playing an important role: KIR2DL1 and KIR2DS1. The aim of this experiment was to determine what responses are generated when decidual NK cells bearing either KIR2DL1 or KIR2DS1 engage their HLA-C ligand.
2014-04-04 | E-MTAB-1784 | biostudies-arrayexpress