-
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 -
Seminars in Immunopathology Nov 2016The decidua has been known as maternal uterine tissue, which plays essential roles in protecting the embryo from being attacked by maternal immune cells and provides... (Review)
Review
The decidua has been known as maternal uterine tissue, which plays essential roles in protecting the embryo from being attacked by maternal immune cells and provides nutritional support for the developing embryo prior to placenta formation. However, there are questions that still remain to be answered: (1) How does the decidua supply nutrition and provide a physical scaffold for the growing embryo, before placental vascular connection is established? (2) How is the balance between preventing an anti-embryo immune response and protecting both embryo and mother from infections established? To understand basic personas in decidual tissues, we review the structure of the decidua composed of terminally differentiated uterine stromal cells, blood vessels, and a number of repertoire of uterine local immune cells, including the well-known uterine natural killer (uNK) cells and recently discovered innate lymphoid cells (ILCs). Decidual macrophages and uterine dendritic cells (DCs) are supposed to modulate adaptive immunity via balancing cytokines and promoting generation of regulatory T (T) cells. During decidualization, vascular and tissue remodeling in the uterus provide nutritional and physical support for the developing embryo. Secretion of various cytokines and chemokines from both the embryo and the decidual cells activates multiple signaling network between the mother and the embryo upon implantation. Defects in the decidual development during early pregnancy result in loss of pregnancy or complications in later gestational stage.
Topics: Animals; Cell Communication; Decidua; Embryonic Development; Endometrium; Female; Humans; Immunity; Immunity, Innate; Killer Cells, Natural; Lymphocyte Subsets; Neovascularization, Physiologic; Pregnancy; Signal Transduction; Uterus
PubMed: 27287066
DOI: 10.1007/s00281-016-0574-0 -
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 -
Journal of Reproductive Immunology Apr 2015The establishment of pregnancy requires the co-ordinated implantation of the embryo into the receptive decidua, placentation, trophoblast invasion of the maternal... (Review)
Review
The establishment of pregnancy requires the co-ordinated implantation of the embryo into the receptive decidua, placentation, trophoblast invasion of the maternal decidua and myometrium in addition to remodelling of the uterine spiral arteries. Failure of any of these steps can lead to a range of pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction, placenta accreta and pre-term birth. Cytokines are small multifunctional proteins often derived from leucocytes and have primarily been described through their immunomodulatory actions. The maternal-fetal interface is considered to be immunosuppressed to allow development of the semi-allogeneic placental fetal unit. However, cytokine profiles of the decidua and different decidual cell types suggest that the in vivo situation might be more complex. Data suggest that decidual-derived cytokines not only play roles in immunosuppression, but also in other aspects of the establishment of pregnancy, including the regulation of trophoblast invasion and spiral artery remodelling. This review focuses on the potential role of decidua-derived cytokines in the aetiology of unexplained spontaneous miscarriage.
Topics: Abortion, Spontaneous; Animals; Cytokines; Decidua; Female; Humans; Immune Tolerance; Maternal-Fetal Exchange; Neovascularization, Physiologic; Pregnancy; Trophoblasts; Uterus
PubMed: 25771398
DOI: 10.1016/j.jri.2015.02.003 -
International Journal of Biological... 2020The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the... (Review)
Review
The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM. Emerging evidence has shown that collagen and its fragment are expressed at the maternal fetal interface. The regulation of expression of collagen is quite complex, and this process involves a multitude of factors. Collagen exerts a critical role during the successful pregnancy. In addition, the abnormal expressions of collagen and its fragments are associated with certain pathological states associated with pregnancy, including recurrent miscarriage, diabetes mellitus with pregnancy, preeclampsia and so on. In this review, the expression and potential roles of collagen under conditions of physiological and pathological pregnancy are systematically discussed.
Topics: Collagen; Decidua; Female; Gene Expression Regulation; Humans; Maternal-Fetal Exchange; Placenta; Pregnancy
PubMed: 32549767
DOI: 10.7150/ijbs.45586 -
Fertility and Sterility Mar 2023To define the decidual microenvironment in euploid and aneuploid missed abortions and elective termination of pregnancies. (Observational Study)
Observational Study
OBJECTIVE
To define the decidual microenvironment in euploid and aneuploid missed abortions and elective termination of pregnancies.
DESIGN
Prospective, multicenter, observational study.
SETTING
Tertiary hospital and descriptive analysis of transcriptomic data.
PATIENT(S)
A total of 34 patients experienced abortions, including 6 women who underwent elective terminations of pregnancy of unplanned pregnancies and 28 cases with missed abortions. All patients underwent their operations from Sep, 2021 to Sep, 2022.
INTERVENTION(S)
All women underwent villous copy number variation sequencing. Meanwhile, single-cell RNA sequencing were performed in the decidual tissues of 16 women, and reverse transcription quantitative polymerase chain reaction were performed in the decidual tissues of 18 women.
MAIN OUTCOME MEASURE(S)
Single-cell RNA sequencing was used to explore the changes in the microenvironment of decidual tissues in abortions.
RESULT(S)
Single-cell RNA sequencing indicated that the microenvironment of the decidual tissue of the missed-abortion group was altered, and that the stromal cells (SCs), natural killer cells, macrophages, and epithelial cells all reflected functional imbalances compared with the elective terminations of pregnancy group. We also noted a correlation between the proportion of senescent SCs and chromosomal abnormalities in missed-abortion embryos. The proportion of senescent decidual SCs in the decidual tissue of missed-abortion patients with common chromosomal abnormalities of the fetus was higher, and this was not conducive to fetal growth and was closely related to missed abortion. In addition, we ascertained that the strength of the HLA-KIR interaction between NK1 and NK2 subsets and non-senescent stromal cell subsets in the missed abortion decidual tissues was weakened, potentially playing a role in the occurrence of missed abortion.
CONCLUSION(S)
The decidualization of SCs in the missed-abortion decidual tissues was impaired, the clearance of senescent SCs by NK cells was weakened, the killing toxicity of non-senescent SCs was enhanced, macrophages were insufficiently resident at the maternal-fetal interface, and epithelial cell differentiation was unbalanced-all creating a maternal microenvironment that was not conducive to fetal growth. We posit that interfering with the expression of dysregulated genes in the missed-abortion decidual tissues and reversing the maternal microenvironment might constitute an effective means toward improving the clinical outcome of missed abortions. Intriguingly, we observed a correlation between stromal cell senescence and embryonic chromosomal abnormalities. Thus, we hypothesize that the DIO2 marker of senescent SCs can be used as a risk indicator for the occurrence of missed miscarriages with chromosomal abnormalities of the embryos, and that it can be applied to guide the clinical diagnosis and treatment of recurrent abortion.
CLINICAL TRIAL REGISTRATION NUMBER
NCT04425317.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Abortion, Missed; Chromosome Aberrations; Decidua; DNA Copy Number Variations; Prospective Studies; Iodothyronine Deiodinase Type II
PubMed: 36528108
DOI: 10.1016/j.fertnstert.2022.12.016 -
Biology of Reproduction Aug 2022Uterine dysfunctions lead to fertility disorders and pregnancy complications. Normal uterine functions at pregnancy depend on crosstalk among multiple cell types in...
Uterine dysfunctions lead to fertility disorders and pregnancy complications. Normal uterine functions at pregnancy depend on crosstalk among multiple cell types in uterine microenvironments. Here, we performed the spatial transcriptomics and single-cell RNA-seq assays to determine local gene expression profiles at the embryo implantation site of the mouse uterus on pregnancy day 7.5 (D7.5). The spatial transcriptomic annotation identified 11 domains of distinct gene signatures, including a mesometrial myometrium, an anti-mesometrial myometrium, a mesometrial decidua enriched with natural killer cells, a vascular sinus zone for maternal vessel remodeling, a fetal-maternal interface, a primary decidual zone, a transition decidual zone, a secondary decidual zone, undifferentiated stroma, uterine glands, and the embryo. The scRNA-Seq identified 12 types of cells in the D7.5 uterus including three types of stromal fibroblasts with differentiated and undifferentiated markers, one cluster of epithelium including luminal and glandular epithelium, mesothelium, endothelia, pericytes, myelomonocytic cell, natural killer cells, and lymphocyte B. These single-cell RNA signatures were then utilized to deconvolute the cell-type compositions of each individual uterine microenvironment. Functional annotation assays on spatial transcriptomic data revealed uterine microenvironments with distinguished metabolic preferences, immune responses, and various cellular behaviors that are regulated by region-specific endocrine and paracrine signals. Global interactome among regions is also projected based on the spatial transcriptomic data. This study provides high-resolution transcriptome profiles with locality information at the embryo implantation site to facilitate further investigations on molecular mechanisms for normal pregnancy progression.
Topics: Animals; Decidua; Embryo Implantation; Epithelium; Female; Killer Cells, Natural; Mice; Myometrium; Pregnancy; Transcriptome; Uterus
PubMed: 35357464
DOI: 10.1093/biolre/ioac061 -
Biomolecules Sep 2022Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose... (Review)
Review
Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose metabolism, reactive oxidative stress, and hormones. The involvement or abnormality of these factors can impair canonical decidualization. Unusual decidualization can lead to perinatal complications, such as disruption of trophoblast invasion. Drastic changes in the morphology and function of human endometrial stromal cells (hESCs) are important for decidualization of the human endometrium; hESCs are used to induce optimal morphological and functional decidualization in vitro because they contain estrogen and progesterone receptors. In this review, we will focus on the studies that have been conducted on hESC decidualization, including the results from our laboratory.
Topics: Cells, Cultured; Decidua; Estrogens; Female; Glucose; Humans; Pregnancy; Receptors, Progesterone; Stromal Cells
PubMed: 36139114
DOI: 10.3390/biom12091275 -
International Journal of Molecular... Oct 2019Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy,... (Review)
Review
Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.
Topics: Abortion, Habitual; Cytokines; Decidua; Dendritic Cells; Embryo, Mammalian; Endometrium; Female; Humans; Killer Cells, Natural; Macrophages; Pregnancy; T-Lymphocytes, Regulatory
PubMed: 31717776
DOI: 10.3390/ijms20215332