TLR5 Supports Development of Placental Labyrinthine Zone in Mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Yiu JHC
PROVIDER: S-EPMC8356041 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
TLR5 Supports Development of Placental Labyrinthine Zone in Mice.
Yiu Jensen H C JHC Cheung Samson W M SWM Cai Jieling J Chan Kam-Suen KS Chen Jing J Cheong Lai Yee LY Chau Hau-Tak HT Xu Aimin A Li Raymond H W RHW Woo Connie W CW
Frontiers in cell and developmental biology 20210728
Toll plays an important role in innate immunity and embryonic development in lower-ranked animals, but in mammals, the homolog toll-like receptors (TLR) are reported to facilitate postnatal development of immunity only. Here, we discovered a role of TLR5 in placental development. <i>Tlr5</i> was highly transcribed during the placenta-forming and functional phases. TLR5 deletion led to a smaller placental labyrinthine zone and lower embryo weight, and the smaller size of embryo was overcorrected, ...[more]
Similar Datasets
Project description:The placenta is an organ that is formed transiently during pregnancy, and appropriate placental development is necessary for fetal survival and growth. Proper differentiation of the labyrinthine layer of the placenta is especially crucial, as it establishes the fetal-maternal interface that is involved in physiological exchange processes. Although previous studies have indicated the importance of inhibitor of differentiation/inhibitor of DNA binding-2 (Id2) helix-loop-helix transcriptional regulator in mediating cell differentiation, the ability of Id2 to regulate differentiation toward the labyrinthine (transport) lineage of the placenta has yet to be determined. In the current study, we have generated labyrinthine trophoblast progenitor cells with increased (SM10-Id2) or decreased (SM10-Id2-shRNA) Id2 expression and determined the effect on TGF-β-induced differentiation. Our Id2 overexpression and knockdown analyses indicate that Id2 mediates TGF-β-induced morphological differentiation of labyrinthine trophoblast cells, as Id2 overexpression prevents differentiation and Id2 knockdown results in differentiation. Thus, our data indicate that Id2 is an important molecular mediator of labyrinthine trophoblast differentiation. An understanding of the regulators of trophoblast progenitor differentiation toward the labyrinthine lineage may offer insights into events governing pregnancy-associated disorders, such as placental insufficiency, fetal growth restriction, and preeclampsia.
| S-EPMC4931356 | biostudies-literature
Project description:The maternal microbiome is an important regulator of gestational health, but how it impacts the placenta as the interface between mother and fetus remains unexplored. Here we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate angiogenesis-related tube formation by endothelial cells and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
| S-EPMC9948959 | biostudies-literature
Project description:The maternal microbiome is an important regulator of gestational health, but how it affects the placenta as the interface between mother and fetus remains unexplored. Here, we show that the maternal gut microbiota supports placental development in mice. Depletion of the maternal gut microbiota restricts placental growth and impairs feto-placental vascularization. The maternal gut microbiota modulates metabolites in the maternal and fetal circulation. Short-chain fatty acids (SCFAs) stimulate cultured endothelial cell tube formation and prevent abnormalities in placental vascularization in microbiota-deficient mice. Furthermore, in a model of maternal malnutrition, gestational supplementation with SCFAs prevents placental growth restriction and vascular insufficiency. These findings highlight the importance of host-microbial symbioses during pregnancy and reveal that the maternal gut microbiome promotes placental growth and vascularization in mice.
| S-EPMC10558122 | biostudies-literature
Project description:Activation of TLRs by bacterial products results in rapid activation of genes encoding products designed to protect the host from perturbing microbes. In the intestine, which is colonized by a large and diverse population of commensal bacteria, TLR signaling may not function in a simple on/off mode. Here, we show that the flagellin receptor TLR5 has an essential and nonredundant role in protecting the gut from enteric microbes. Mice lacking TLR5 (TLR5KO mice) developed spontaneous colitis, as assessed by well-defined clinical, serologic, and histopathologic indicators of this disorder. Compared with WT littermates, TLR5KO mice that had not yet developed robust colitis exhibited decreased intestinal expression of TLR5-regulated host defense genes despite having an increased bacterial burden in the colon. In contrast, such TLR5KO mice displayed markedly increased colonic expression of hematopoietic-derived proinflammatory cytokines, suggesting that elevated levels of bacterial products may result in activation of other TLRs that drive colitis in TLR5KO mice. In accordance, deletion of TLR4 rescued the colitis of TLR5KO mice in that mice lacking both TLR4 and TLR5 also had elevated bacterial loads in the colon but lacked immunological, histopathological, and clinical evidence of colitis. That an engineered innate immune deficiency ultimately results in spontaneous intestinal inflammation supports the notion that an innate immune deficiency might underlie some instances of inflammatory bowel disease.
| S-EPMC2075480 | biostudies-literature
Project description:BackgroundEpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells.Methodology/principal findingsTo gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas.ConclusionEpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.
| S-EPMC2796178 | biostudies-literature
Project description:Self-organisation is a ubiquitous phenomenon in ecosystems. These systems can experience transitions from a uniform cover towards the formation of vegetation patterns as a result of symmetry-breaking instability. They can be either periodic or localised in space. Localised vegetation patterns consist of more or less circular spots or patches that can be either isolated or randomly distributed in space. We report on a striking patterning phenomenon consisting of localised vegetation labyrinths. This intriguing pattern is visible in satellite photographs taken in many territories of Africa and Australia. They consist of labyrinths which is spatially irregular pattern surrounded by either a homogeneous cover or a bare soil. The phenomenon is not specific to particular plants or soils. They are observed on strictly homogenous environmental conditions on flat landscapes, but they are also visible on hills. The spatial size of localized labyrinth ranges typically from a few hundred meters to ten kilometres. A simple modelling approach based on the interplay between short-range and long-range interactions governing plant communities or on the water dynamics explains the observations reported here.
| S-EPMC8443762 | biostudies-literature
Project description:IntroductionPlacental insufficiency, arising from abnormal trophoblast differentiation and function, is a major cause of fetal growth restriction. Sirtuin-1 (Sirt1) is a ubiquitously-expressed NAD-dependent protein deacetylase which plays a key role in numerous cellular processes, including cellular differentiation and metabolism. Though Sirt1 has been widely studied, its role in placentation and trophoblast differentiation is unclear.MethodSirt1-heterozygous mice were mated and evaluated at various points during embryogenesis. In situ hybridization and immunohistochemistry were used to further characterize the placental phenotype of Sirt1-null mice. Wild-type (WT) and Sirt1-null mouse trophoblast stem cell (TSC) lines were derived from e3.5 littermate blastocysts. These cells were then evaluated at various points following differentiation. Differentiation was evaluated by expression of lineage specific markers using qPCR and flow cytometry, as well as Matrigel invasion assays. Global gene expression changes were evaluated using microarray-based RNA profiling; changes in specific pathways were validated using qPCR and western blot.ResultsIn the absence of Sirt1, both embryos and placentas were small, with placentas showing abnormalities in both the labyrinthine layer and junctional zone. Sirt1-null TSCs exhibited an altered phenotype in both undifferentiated and differentiated states, phenotypes which corresponded to changes in pathways relevant to both TSC maintenance and differentiation. Specifically, Sirt1-null TSC showed blunted differentiation, and appeared to be suspended in an Epcamhigh trophoblast progenitor state.DiscussionOur results suggest that Sirt1 is required for proper TSC differentiation and placental development.
| S-EPMC5805473 | biostudies-literature
Project description:Triclosan (TCS) is associated with spontaneous abortions and fetal growth restriction. Here, we showed that when pregnant mice were treated with 8 mg/kg TCS (8-TCS mice) on gestational days (GD) 6-18 fetal body weights were lower than controls. Placental weights and volumes were reduced in 8-TCS mice. The placental proliferative cells and expression of PCNA and Cyclin D3 on GD13 were remarkably decreased in 8-TCS mice. The decreases in activities and expression of placental System A amino acid or glucose transporters on GD14 and GD17 were observed in 8-TCS mice. Levels of serum thyroxine (T4) and triiodothyronine (T3) were lower in 8-TCS mice than those in controls. Declines of placental Akt, mTOR and P70S6K phosphorylation in 8-TCS mice were corrected by L-thyroxinein (T4). Treating 8-TCS mice with T4 rescued the placental cell proliferation and recovered the activity and expression of amino acid and glucose transporters, which were sensitive to mTOR inhibition by rapamycin. Furthermore, the replacement of T4 could rescue the decrease in fetal body weight, which was blocked by rapamycin. These findings indicate that TCS-induced hypothyroxinemia in gestation mice through reducing Akt-mTOR signaling may impair placental development and nutrient transfer leading to decreases in fetal body weight.
| S-EPMC5359620 | biostudies-literature
Project description:Study hypothesisPlacental growth factor (PGF) is expressed in the developing mouse brain and contributes to vascularization and vessel patterning.Study findingPGF is dynamically expressed in fetal mouse brain, particularly forebrain, and is essential for normal cerebrovascular development.What is known alreadyPGF rises in maternal plasma over normal human and mouse pregnancy but is low in many women with the acute onset hypertensive syndrome, pre-eclampsia (PE). Little is known about the expression of PGF in the fetus during PE. Pgf (-/-) mice appear normal but recently cerebral vascular defects were documented in adult Pgf (-/-) mice.Study design, samples/materials, methodsHere, temporal-spatial expression of PGF is mapped in normal fetal mouse brains and cerebral vasculature development is compared between normal and congenic Pgf (-/-) fetuses to assess the actions of PGF during cerebrovascular development. Pgf/PGF, Vegfa/VEGF, Vegf receptor (Vegfr)1 and Vegfr2 expression were examined in the brains of embryonic day (E)12.5, 14.5, 16.5 and 18.5 C57BL/6 (B6) mice using quantitative PCR and immunohistochemistry. The cerebral vasculature was compared between Pgf (-/-) and B6 embryonic and adult brains using whole mount techniques. Vulnerability to cerebral ischemia was investigated using a left common carotid ligation assay.Main results and the role of chancePgf/PGF and Vegfr1 are highly expressed in E12.5-14.5 forebrain relative to VEGF and Vegfr2. Vegfa/VEGF is relatively more abundant in hindbrain (HB). PGF and VEGF expression were similar in midbrain. Delayed HB vascularization was seen at E10.5 and 11.5 in Pgf (-/-) brains. At E14.5, Pgf (-/-) circle of Willis showed unilateral hypoplasia and fewer collateral vessels, defects that persisted post-natally. Functionally, adult Pgf (-/-) mice experienced cerebral ischemia after left common carotid arterial occlusion while B6 mice did not.Limitations, reasons for cautionSince Pgf (-/-) mice were used, consequences of complete absence of maternal and fetal PGF were defined. Therefore, the effects of maternal versus fetal PGF deficiency on cerebrovascular development cannot be separated. However, as PGF was strongly expressed in the developing brain at all timepoints, we suggest that local PGF has a more important role than distant maternal or placental sources. Full PGF loss is not expected in PE pregnancies, predicting that the effects of PGF deficiency identified in this model will be more severe than any effects in PE-offspring.Wider implications of the findingsThese studies provoke the question of whether PGF expression is decreased and cerebral vascular maldevelopment occurs in fetuses who experience a preeclamptic gestation. These individuals have already been reported to have elevated risk for stroke and cognitive impairments.Large scale dataN/A.Study funding and competing interestsThis work was supported by awards from the Natural Sciences and Engineering Research Council, the Canada Research Chairs Program and the Canadian Foundation for Innovation to B.A.C. and by training awards from the Universidade Federal de Pernambuco and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil to R.L.L.; Queen's University to V.R.K. and the Canadian Institutes of Health Research to M.T.R. The work of P.C. is supported by the Belgian Science Policy BELSPO-IUAP7/03, Structural funding by the Flemish Government-Methusalem funding, and the Flemish Science Fund-FWO grants. There were no competing interests.
| S-EPMC4733225 | biostudies-literature
Project description:The placental vasculature is critical for nutrient, gas, and waste exchange between the maternal and fetal systems. Its development depends on the proper expression and interaction of angiogenesis and associated growth factors. Heme oxygenase (HMOX), the enzyme for heme degradation, plays a role in angiogenesis and is highly expressed in the placenta. To evaluate the role of maternal HMOX1, the inducible HMOX isozyme, on placental vasculature formation, mice with a partial deficiency in Hmox1 (Hmox1(+/-)) were used. Three-dimensional images of placental vasculatures as well as spiral arteries from Hmox1(+/+) or Hmox1(+/-) placentas were created by vascular corrosion casting technique and imaged by micro-computerized tomography (microCT). The structures and morphologies of fetomaternal interfaces were observed by histological staining and the ultrastructure of uterine natural killer (uNK) cells, a major regulator in spiral artery remodeling, was analyzed by transmission electron microscopy. A group of growth factors and angiogenic factors from the decidua/mesometrial lymphoid aggregate of pregnancy (MLAp) as well as labyrinth regions were quantified using an angiogenesis PCR array kit and compared between Hmox1(+/+) or Hmox1(+/-) placentas. In conclusion, a partial deficiency of maternal Hmox1 resulted in the malformation of fetomaternal interface, insufficiency of spiral artery remodeling, and alteration of uNK cell differentiation and maturation. These changes were independent of the fetal genotype, but relied on the maternal HMOX1 level, which determined the balance of expression levels of pro- and antiangiogenic factors in the decidua/MLAp region. These results implied that Hmox1 polymorphisms among the human population might contribute to some unexplained cases of pregnancy disorders, such as fetal growth retardation and preeclampsia.
| S-EPMC3197918 | biostudies-literature