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Cell Reports Jul 2023Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains...
Leukocyte diversity of the first-trimester maternal-fetal interface has been extensively described; however, the immunological landscape of the term decidua remains poorly understood. We therefore profiled human leukocytes from term decidua collected via scheduled cesarean delivery. Relative to the first trimester, our analyses show a shift from NK cells and macrophages to T cells and enhanced immune activation. Although circulating and decidual T cells are phenotypically distinct, they demonstrate significant clonotype sharing. We also report significant diversity within decidual macrophages, the frequency of which positively correlates with pregravid maternal body mass index. Interestingly, the ability of decidual macrophages to respond to bacterial ligands is reduced with pregravid obesity, suggestive of skewing toward immunoregulation as a possible mechanism to safeguard the fetus against excessive maternal inflammation. These findings are a resource for future studies investigating pathological conditions that compromise fetal health and reproductive success.
Topics: Pregnancy; Female; Humans; Decidua; T-Lymphocytes; Reproduction; Killer Cells, Natural; Macrophages
PubMed: 37432849
DOI: 10.1016/j.celrep.2023.112769 -
Frontiers in Immunology 2023
Topics: Pregnancy; Female; Humans; Abortion, Habitual; Decidua
PubMed: 38022573
DOI: 10.3389/fimmu.2023.1330701 -
Frontiers in Immunology 2019A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms.... (Review)
Review
A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms. Infection with pathogenic microorganisms during pregnancy may lead to premature delivery, miscarriage, growth restriction, neonatal morbidity, and other adverse outcomes. Moreover, the host also has an intact immune system to avoid these adverse outcomes. It is important to note the presence of normal bacteria in the maternal reproductive tract and the principal role of the maternal-placental-fetal interaction in antimicrobial immunity. Previous studies mainly focused on maternal infection during pregnancy. However, this review summarizes the new views on the study of the maternal microbiome and expounds the innate immune defense mechanism of the maternal vagina and decidua as well as how cytotrophoblasts and syncytiotrophoblasts recognize and kill bacteria in the placenta. Fetal immune systems, thought to be weak, also exhibit an immune defense function that is indispensable for maintaining the safety of the fetus. The skin, lungs, and intestines of the fetus during pregnancy constitute the main immune barriers. These findings will provide a new understanding of the effects of normal microbial flora and how the host resists harmful microbes during pregnancy. We believe that it may also contribute to the reference on the clinical prevention and treatment of gestational infection to avoid adverse pregnancy outcomes.
Topics: Decidua; Female; Humans; Immunity, Innate; Maternal-Fetal Exchange; Microbiota; Pregnancy; Pregnancy Complications; Trophoblasts; Vagina
PubMed: 31921149
DOI: 10.3389/fimmu.2019.02886 -
Frontiers in Immunology 2023Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the...
BACKGROUND
Preeclampsia is a pregnancy-specific disorder that always causes maternal and fetal serious adverse outcome. Disturbances in maternal immune tolerance to embryo at the maternal-fetal interface (MFI) may be associated with preeclampsia onset. Recent studies have revealed the reduced expression pattern of HLA-F at the MFI in preeclampsia, while the mechanism of it mediating maternal fetal immune tolerance has not been revealed.
METHODS
Single-cell RNA sequencing on placental decidua was performed to reveal the immune disturbances landscape at the MFI in preeclampsia. Human Jar cells and NK-92MI cells were employed to study the role of HLA-F in trophoblasts and lymphocyte.
RESULTS
A total of 101,250 cells were classified into 22 cell clusters. Disease-related IGFBP1+SPP1+ extracellular villus trophoblast (EVT) was identified in the preeclamptic placental decidua, accompanied by newly discovered immune cellular dysfunction such as reduced ribosomal functions of NK populations and abnormal expression of antigen-presenting molecules in most cell clusters. Certain genes that are characteristic of the intermediate stage of myeloid or EVT cell differentiation were found to have unexplored but important functions in the pathogenesis of preeclampsia; specifically, we detected enhanced cell cross-talk between IGFBP1+SPP1+ EVT2 or SPP1+M1 cells and their receptor cell populations at the MFI of PE patients compared to controls. With respect to HLA-F, mIF staining confirmed its reduced expression in PE samples compared to controls. Over-expression of HLA-F in Jar cells promoted cell proliferation, invasion, and migration while under-expression had the opposite effect. In NK-92MI cells, over-expression of HLA-F increased the secretion of immunoregulation cytokines such as CSF1 and CCL22, and promoted adaptive NKG2C+NK cell transformation.
CONCLUSIONS
We revealed the immune disturbance landscape at the MFI in preeclampsia. Our findings regarding cellular heterogeneity and immune cellular dysfunction, as revealed by scRNA-seq, and the function of HLA-F in cells provide new perspectives for further investigation of their roles in the pathogenesis of preeclampsia, and then provide potential new therapeutic target.
Topics: Female; Humans; Pregnancy; Decidua; Immune Tolerance; Killer Cells, Natural; Placenta; Pre-Eclampsia
PubMed: 37854606
DOI: 10.3389/fimmu.2023.1234577 -
The Journal of Steroid Biochemistry and... May 2023Progesterone is a sex steroid hormone that plays a critical role in the establishment and maintenance of pregnancy. This hormone drives numerous maternal physiological... (Review)
Review
Progesterone is a sex steroid hormone that plays a critical role in the establishment and maintenance of pregnancy. This hormone drives numerous maternal physiological adaptations to ensure the continuation of pregnancy and to facilitate fetal growth, including broad and potent modulation of the maternal immune system to promote maternal-fetal tolerance. In this brief review, we provide an overview of the immunomodulatory functions of progesterone in the decidua, placenta, myometrium, and maternal circulation during pregnancy. Specifically, we summarize current evidence of the regulated functions of innate and adaptive immune cells induced by progesterone and its downstream effector molecules in these compartments, including observations in human pregnancy and in animal models. Our review highlights the gaps in knowledge of interactions between progesterone and maternal cellular immunity that may direct future research.
Topics: Pregnancy; Female; Animals; Humans; Progesterone; Decidua; Placenta; Immune System; Maternal-Fetal Exchange
PubMed: 36681283
DOI: 10.1016/j.jsbmb.2023.106254 -
PloS One 2021Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a...
Inflammation is thought to play a pivotal role in the onset of term and some forms of preterm labour. Although, we recently found that myometrial inflammation is a consequence rather than a cause of term labour, there are several other reproductive tissues, including amnion, choriodecidua parietalis and decidua basalis, where the inflammatory stimulus to labour may occur. To investigate this, we have obtained amnion, choriodecidual parietalis and decidua basalis samples from women at various stages of pregnancy and spontaneous labour. The inflammatory cytokine profile in each tissue was determine by Bio-Plex Pro® cytokine multiplex assays and quantitative RT-PCR. Active motif assay was used to study transcription activation in the choriodecidua parietalis. Quantitative RT-PCR was use to study the pro-labour genes (PGHS-2, PGDH, OTR and CX43) in all of the tissues at the onset of labour and oxytocin (OT) mRNA expression in the choriodecidual parietalis and decidua basalis. Statistical significance was ascribed to a P value <0.05. In the amnion and choriodecidua parietalis, the mRNA levels of various cytokines decreased from preterm no labour to term no labour samples, but the protein levels were unchanged. The choriodecidua parietalis showed increase in the protein levels of IL-1β and IL-6 in the term early labour samples. In the amnion and decidua basalis, the protein levels of several cytokines rose in term established labour. The multiples of the median derived from the 19-plex cytokine assay were greater in term early labour and term established labour samples from the choriodecidua parietalis, but only in term established labour for myometrium. These data suggest that the inflammatory stimulus to labour may begin in the choriodecidua parietalis, but the absence of any change in prolabour factor mRNA levels suggests that the cytokines may act on the myometrium where we observed changes in transcription factor activation and increases in prolabour gene expression in earlier studies.
Topics: CX3C Chemokine Receptor 1; Cytokines; Decidua; Female; Humans; Inflammation; Interleukin-10; Interleukin-6; Labor, Obstetric; Myometrium; Polymerase Chain Reaction; Pregnancy
PubMed: 34464407
DOI: 10.1371/journal.pone.0256545 -
Life (Basel, Switzerland) Apr 2023Due to a vast influx in the secretory phase of the menstrual cycle, leukocytes represent 40-50% of the decidua at the time of implantation. Their importance for the... (Review)
Review
Due to a vast influx in the secretory phase of the menstrual cycle, leukocytes represent 40-50% of the decidua at the time of implantation. Their importance for the implantation, maintenance of pregnancy, and parturition are known yet not fully understood. Thus, in idiopathic infertility, decidual immune-related factors are speculated to be the cause. In this review, the immune cell functions in the decidua were summarized, and clinical diagnostics, as well as interventions, were discussed. There is a rising number of commercially available diagnostic tools. However, the intervention options are still limited and/or poorly studied. In order for us to make big steps towards the proper use of reproductive immunology findings, we need to understand the mechanisms and especially support translational research.
PubMed: 37240742
DOI: 10.3390/life13051097 -
International Journal of Molecular... Feb 2022Preterm birth remains to be one of the most prevalent obstetric complications worldwide. Since there are multiple etiological factors associated with this disease... (Review)
Review
Preterm birth remains to be one of the most prevalent obstetric complications worldwide. Since there are multiple etiological factors associated with this disease process, an integrative literature search in PubMed and Scopus databases on possible mechanism of action and effect of bisphenols on exposure on human or animal placental samples in preterm birth was conducted. From 2332 articles on initial literature search, 63 studies were included for full data extraction. Altogether, several pathways were shown to be possibly affected by bisphenols, leading to dysregulations in structural and endocrine foundation in the placenta, potential induction of senescence and failure of decidualization in the decidua, and possible propagation of inflammation in the fetal membranes. Combined, these actions may eventually counteract bisphenol-induced relaxation of the myometrium and promote contractility alongside fetal membrane weakening. In totality, these individual impairments in gestation-critical processes may lead to failure of maintenance of pregnancy, and thus effecting preterm birth.
Topics: Benzhydryl Compounds; Cellular Senescence; Decidua; Female; Gene Expression Regulation; Humans; Phenols; Pregnancy; Premature Birth; Signal Transduction
PubMed: 35269554
DOI: 10.3390/ijms23052411 -
International Journal of Molecular... Dec 2022Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure...
Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFβ, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.
Topics: Pregnancy; Female; Humans; Proto-Oncogene Proteins c-akt; Cilia; Phosphatidylinositol 3-Kinases; Endometrium; Signal Transduction; Stromal Cells; Decidua
PubMed: 36555215
DOI: 10.3390/ijms232415573 -
IScience Oct 2023The underlying mechanisms governing parturition remain largely elusive due to limited knowledge of parturition preparation and initiation. Accumulated evidences indicate...
The underlying mechanisms governing parturition remain largely elusive due to limited knowledge of parturition preparation and initiation. Accumulated evidences indicate that maternal decidua plays a critical role in parturition initiation. To comprehensively decrypt the cell heterogeneity in decidua approaching parturition, we investigate the roles of various cell types in mouse decidua process and reveal previously unappreciated insights in parturition initiation utilizing single-cell RNA sequencing (scRNA-seq). We enumerate the cell types in decidua and identity five different stromal cells populations and one decidualized stromal cells. Furthermore, our study unravels that stromal cells prepare for parturition by regulating local retinol acid (RA) synthesis. RA supplement decreases expression of extracellular matrix-related genes and accelerates the timing of parturition . Collectively, the discovery of contribution of stromal cells in parturition expands current knowledge about parturition and opens up avenues for the intervention of preterm birth (PTB).
PubMed: 37720083
DOI: 10.1016/j.isci.2023.107796