-
Biology of Reproduction Aug 2023The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the...
The fallopian tubes (FTs) are part of the female upper genital tract. The healthy FT provides the biological environment for successful fertilization and facilitates the subsequent movement of the conceptus to the endometrial cavity. However, when the FT is damaged, as with salpingitis, pyosalpinx, and hydrosalpinx, it may increase the risk of an ectopic pregnancy, a life-threatening condition. Decidualization refers to a multifactorial process by which the endometrium changes to permit blastocyst implantation. The decidualization reaction is vital for endometrial receptivity during the window of implantation. To date, no comprehensive review that collates evidence on decidualization in the human FT has been conducted. Therefore, the aim of this review is to compile the current evidence on cellular decidualization occurring in the healthy and pathological FT in women of reproductive age. A literature search was conducted using five databases and identified 746 articles, 24 of which were analyzed based on inclusion and exclusion criteria. The available evidence indicates that the FT are able to undergo decidual changes under specific circumstances; however, the exact mechanism by which this occurs is poorly understood. Further research is needed to elucidate the mechanism by which decidualization can occur in the FT.
Topics: Pregnancy; Female; Humans; Fallopian Tubes; Endometrium; Embryo Implantation; Uterus; Decidua; Stromal Cells
PubMed: 37265359
DOI: 10.1093/biolre/ioad062 -
Heliyon Dec 2023NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing...
NK cells infiltrating Hepatocellular Carcinoma (HCC) may express residency markers such as Integrin Subunit Alpha 1 (CD49a) that have been associated with nurturing functions in the decidua, and characterized by the production of angiogenic factors as well as loss of cytotoxicity. CIBERSORT, a computational analysis method for quantifying cell fractions from bulk tissue gene expression profiles, was used to estimate the infiltrating immune cell composition of the tumor microenvironment from gene expression profiles of a large cohort of 225 HCCs in the public GEO database. Decidual-like CD49a+ NK cells, in addition to another 22 immune cell populations, were characterized and thoroughly investigated so that HCC cell heterogeneity in a large cohort of 225 HCCs from the public GEO database could be studied. An inverse correlation of the expression of CD49a+ NK-cells and CD8 T-cells suggested a negative association with clinical outcomes. This result was confirmed in a further validation cohort of 100 HCC patients from The Cancer Genome Atlas, Liver Hepatocellular Carcinoma (TCGA-LIHC). Cox regression analysis did not identify CD49a+ cells as a variable independently associated with survival. However, a more abundant infiltrate of this subset was present in patients at a more advanced pathological and clinical HCC stage. In conclusion, we found that NK cells, with a decidual-like gene expression profile, are enriched in HCC, and their abundance increases not only in tumor size but also at advanced stages of the disease suggesting that these cells play a role in tumor growth. For this reason, these NK cells may represent a possible new target for immunotherapeutic approaches in HCC.
PubMed: 38107324
DOI: 10.1016/j.heliyon.2023.e22680 -
Frontiers in Immunology 2024IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL)....
INTRODUCTION
IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).
METHODS
Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.
RESULTS
IUI induced a robust expression of mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.
DISCUSSION
These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.
Topics: Female; Pregnancy; Humans; Animals; Interleukin-6; Signal Transduction; Macaca mulatta; Tumor Necrosis Factor-alpha; Chorioamnionitis; Lipopolysaccharides; Interleukin-1; Adult; Obstetric Labor, Premature; Inflammation; Interleukin 1 Receptor Antagonist Protein; Placenta
PubMed: 38895127
DOI: 10.3389/fimmu.2024.1416162 -
Placenta Aug 2023The human placenta comes in direct contact with maternal cells and blood at two interfaces. The syncytiotrophoblast layer is surrounded by maternal blood at the...
The human placenta comes in direct contact with maternal cells and blood at two interfaces. The syncytiotrophoblast layer is surrounded by maternal blood at the intervillous space, and extravillous trophoblasts breach the vascular endothelial cells layer upon spiral artery remodeling and invasion of decidual veins. However, little knowledge exists about EVT-derived secreted factors, which may serve as predictive markers for obstetrical syndromes or shape the local environment at the maternal-fetal interface. Here, we define secreted EVT-associated genes and describe a method that yields interstitial fluids from patient-matched first-trimester decidua basalis and parietalis tissues.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, First; Placentation; Extracellular Fluid; Decidua; Endothelial Cells; Trophoblasts; Proteins
PubMed: 37390517
DOI: 10.1016/j.placenta.2023.06.008 -
STAR Protocols Sep 2023The lack of a suitable explant culture system restricts the study of factors secreted by the mouse placenta into maternal circulation. Here, we present a protocol for...
The lack of a suitable explant culture system restricts the study of factors secreted by the mouse placenta into maternal circulation. Here, we present a protocol for culturing the endocrine junctional zone of the mouse placenta, free from the decidua and labyrinthine layers in serum-free medium. We describe steps for dissecting and separating layers, dicing tissue, and culture setup. We then detail medium processing for downstream analysis. This model allows the investigation of placental signals that may regulate maternal physiology. For complete details on the use and execution of this protocol, please refer to Yung et al. (2023)..
Topics: Mice; Animals; Pregnancy; Female; Placenta
PubMed: 37384519
DOI: 10.1016/j.xpro.2023.102384 -
Heliyon Jan 2024Inflammatory and autoimmune diseases are among the most challenging disorders for health care professionals that require systemic immune suppression which associates...
Inflammatory and autoimmune diseases are among the most challenging disorders for health care professionals that require systemic immune suppression which associates with various side effects. Mesenchymal stromal cells (MSCs) are capable of regulating immune responses, mainly through paracrine effects and cell-cell contact. Since MSCs are advanced therapy medicinal products (ATMPs), they must follow Good Manufacturing Practice (GMP) regulations to ensure their safety and efficacy. In this study, we evaluated the immunomodulatory effects of GMP-compliant clinical grade MSCs obtained from four different sources (bone marrow, adipose tissue, Wharton's Jelly, and decidua tissue) on allogeneic peripheral blood mononuclear cells (PBMCs). Our results revealed that WJ-MSCs were the most successful group in inhibiting PBMC proliferation as confirmed by BrdU analysis. Moreover, WJ-MSCs were the strongest group in enhancing the regulatory T cell population of PBMCs. WJ-MSCs also had the highest secretory profile of prostaglandin E2 (PGE-2), anti-inflammatory cytokine, while interleukin-10 (IL-10) secretion was highest in the DS-MSC group. DS-MSCs also had the lowest secretion of IL-12 and IL-17 inflammatory cytokines. Transcriptome analysis revealed that WJ-MSCs had the lowest expression of IL-6, while DS-MSCs were the most potent group in the expression of immunomodulatory factors such as hepatocyte growth factor (HGF) and transforming growth factor-β (TGF- β). Taken together, our results indicated that GMP-compliant Wharton's Jelly and decidua-derived MSCs showed the best immunomodulatory performance considering paracrine factors.
PubMed: 38312681
DOI: 10.1016/j.heliyon.2024.e24948 -
Journal of Translational Medicine May 2024Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo...
BACKGROUND
Miscarriage is a frustrating complication of pregnancy that is common among women of reproductive age. Insufficient decidualization which not only impairs embryo implantation but disturbs fetomaternal immune-tolerance, has been widely regarded as a major cause of miscarriage; however, the underlying mechanisms resulting in decidual impairment are largely unknown.
METHODS
With informed consent, decidual tissue from patients with spontaneous abortion or normal pregnant women was collected to detect the expression profile of UCHL1. Human endometrial stromal cells (HESCs) were used to explore the roles of UCHL1 in decidualization and dNK modulation, as well as the mechanisms involved. C57/BL6 female mice (7-10 weeks old) were used to construct pregnancy model or artificially induced decidualization model to evaluate the effect of UCHL1 on mice decidualization and pregnancy outcome.
RESULTS
The Ubiquitin C-terminal hydrolase L1 (UCHL1), as a deubiquitinating enzyme, was significantly downregulated in decidua from patients with miscarriage, along with impaired decidualization and decreased dNKs. Blockage of UCHL1 led to insufficient decidualization and resultant decreased expression of cytokines CXCL12, IL-15, TGF-β which were critical for generation of decidual NK cells (dNKs), whereas UCHL1 overexpression enhanced decidualization accompanied by increase in dNKs. Mechanistically, the promotion of UCHL1 on decidualization was dependent on its deubiquitinating activity, and intervention of UCHL1 inhibited the activation of JAK2/STAT3 signaling pathway, resulting in aberrant decidualization and decreased production of cytokines associated with dNKs modulation. Furthermore, we found that inhibition of UCHL1 also disrupted the decidualization in mice and eventually caused adverse pregnancy outcome.
CONCLUSIONS
UCHL1 plays significant roles in decidualization and dNKs modulation during pregnancy in both humans and mice. Its deficiency indicates a poor pregnancy outcome due to defective decidualization, making UCHL1 a potential target for the diagnosis and treatment of miscarriage.
Topics: Ubiquitin Thiolesterase; Female; Decidua; Animals; Pregnancy; Abortion, Spontaneous; Humans; Mice, Inbred C57BL; Killer Cells, Natural; Adult; Mice; Stromal Cells; Signal Transduction
PubMed: 38769534
DOI: 10.1186/s12967-024-05253-0 -
Materials (Basel, Switzerland) Aug 2023The mechanical strength of wood from Scots pine (), European larch (), and Norway spruce () was studied using static compression tests. The material was exposed under...
The mechanical strength of wood from Scots pine (), European larch (), and Norway spruce () was studied using static compression tests. The material was exposed under constant soaking in water with salinity of 7‱. The liquid mix was prepared according to a value roughly equivalent to the average salinity along the entire length of the Baltic Sea. The mechanical strength and quality of the raw material were determined using a sea salt saturation test, which determined the adhesion of the raw material to the extrusion process (permissible stress). An investigation was conducted to determine the physicochemical parameters of the material that was tested. It was investigated how much mineral compounds were absorbed over four cycles lasting a total of six weeks during the test. According to the statistical analysis, the chemical composition of wood and the presence of salts and mineral compounds correlated with its mechanical strength. An important part of the study focused on examining the factors affecting the construction of coniferous wood structures. The preparation of the raw material correctly can provide information on how the material can be protected during exposure to specific environmental conditions for longer.
PubMed: 37687524
DOI: 10.3390/ma16175831 -
Biology Mar 2024The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and...
The etiopathogenesis of preeclampsia, a leading hypertensive disorder of pregnancy, has been proposed to involve an abnormal circulating sex hormone profile and misexpression of placental estrogen and progesterone receptors (ER and PR, respectively). However, existing research is vastly confined to third trimester preeclamptic placentas. Consequently, the placental-uterine molecular crosstalk and the dynamic ER and PR expression pattern in the peri-conception period remain overlooked. Herein, our goal was to use the BPH/5 mouse to elucidate pre-pregnancy and early gestation Er and Pr dynamics in a preeclamptic-like uterus. BPH/5 females display low circulating estrogen concentration during proestrus, followed by early gestation hypoestrogenemia, hyperprogesteronemia, and a spontaneous preeclamptic-like phenotype. Preceding pregnancy, the gene encoding Er alpha (Erα, ) is upregulated in the diestrual BPH/5 uterus. At the peak of decidualization, , Er beta (Erβ, ), and Pr isoform B () were upregulated in the BPH/5 maternal-fetal interface. At the protein level, BPH/5 females display higher percentage of decidual cells with nuclear Erα expression, as well as Pr downregulation in the decidua, luminal and glandular epithelium. In conclusion, we provide evidence of disrupted sex hormone signaling in the peri-conception period of preeclamptic-like pregnancies, potentially shedding some light onto the intricate role of sex hormone signaling at unexplored timepoints of human preeclampsia.
PubMed: 38534461
DOI: 10.3390/biology13030192 -
Environmental Monitoring and Assessment Dec 2023The seedlings of some tree species can successfully develop in areas polluted by heavy metals. Research on such species is important in order to explore the possibility...
The seedlings of some tree species can successfully develop in areas polluted by heavy metals. Research on such species is important in order to explore the possibility of introducing tree species for the permanent biological stabilization and reclamation of post-flotation tailings, especially after the final recycling of trace metals, but where concentrations remain much higher than in natural soils. To better understand the adaptation and reaction of Betula pendula Roth., Pinus sylvestris L., and Larix decidua Mill. seedlings to heavy metals pollution caused by tailings waste highly contaminated by trace elements: 1) the relationships between the concentration of heavy metals in the soil substrate, the efficiency of heavy metal ions accumulation in plant organs, and the biometric parameters of the seedlings; and 2) the threshold content of heavy metals in the roots above which the plant physiological response is triggered was determined. We assume that there are certain limit concentrations of heavy metals in the soil and fine roots, which depend on the tree species and beyond which the plant responds strongly to stressThe obtained results showed that Betula is a suitable species for the phytostabilization of post-flotation tailings due to its rapid growth rate and production of root biomass. The accumulation of metals in Betula roots was found to be much greater than in Pinus and Larix. Despite the high concentrations of heavy metals in the prepared substrates, there was only a slight transfer of these elements to the aboveground parts of the plant. At high soil concentrations, the heavy metals adversely affected the cellular and physiological processes of plants. In plants growing in such conditions, the activity of the antioxidant system depended both on the species and organ of the plant, as well as on the type and metal concentration.
Topics: Trace Elements; Pinus sylvestris; Larix; Environmental Monitoring; Metals, Heavy; Betula; Soil; Soil Pollutants
PubMed: 38110766
DOI: 10.1007/s10661-023-12134-4