-
International Journal of Biological... 2022In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions,... (Review)
Review
In some cases of spontaneous miscarriage (SM), the exact etiology cannot be determined. Autophagy, which is responsible for cellular survival under stress conditions, has also been implicated in many diseases. Recently, it is also surmised to be correlated with SM. However, the detailed mechanism remains elusive. In fact, there are several essential steps during pregnancy establishment and maintenance: trophoblasts invasion, placentation, decidualization, enrichment and infiltration of decidua immune cells (e.g., natural killer, macrophage and T cells). Accordingly, upstream molecules and downstream effects of autophagy are discussed in these processes, respectively. Of note, autophagy regulates the crosstalk between these cells at the maternal-fetal interface as well. Aberrant autophagy is found in villi, decidual stromal cells, peripheral blood mononuclear cells in SM patients, although the findings are inconsistent among different studies. Furthermore, potential treatments targeting autophagy are included, during which rapamycin and vitamin D are hot-spots in recent literatures. To conclude, a moderately activated autophagy is deeply involved in pregnancy, suggesting that autophagy should be a regulator and promising target for treating SM.
Topics: Abortion, Spontaneous; Autophagy; Decidua; Female; Humans; Leukocytes, Mononuclear; Pregnancy; Trophoblasts
PubMed: 35173545
DOI: 10.7150/ijbs.68335 -
ELife Jul 2023Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful...
Decidualization is a process in which endometrial stromal fibroblasts differentiate into specialized secretory decidual cells and essential for the successful establishment of pregnancy. The underlying mechanism during decidualization still remains poorly defined. Because decidualization and fibroblast activation share similar characteristics, this study was to examine whether fibroblast activation is involved in decidualization. In our study, fibroblast activation-related markers are obviously detected in pregnant decidua and under in vitro decidualization. ACTIVIN A secreted under fibroblast activation promotes in vitro decidualization. We showed that arachidonic acid released from uterine luminal epithelium can induce fibroblast activation and decidualization through PGI and its nuclear receptor PPARδ. Based on the significant difference of fibroblast activation-related markers between pregnant and pseudopregnant mice, we found that embryo-derived TNF promotes CPLA phosphorylation and arachidonic acid release from luminal epithelium. Fibroblast activation is also detected under human in vitro decidualization. Similar arachidonic acid-PGI-PPARδ-ACTIVIN A pathway is conserved in human endometrium. Collectively, our data indicate that embryo-derived TNF promotes CPLA phosphorylation and arachidonic acid release from luminal epithelium to induce fibroblast activation and decidualization.
Topics: Pregnancy; Female; Humans; Animals; Mice; Decidua; PPAR delta; Arachidonic Acid; Endometrium; Fibroblasts; Stromal Cells
PubMed: 37458359
DOI: 10.7554/eLife.82970 -
Frontiers in Immunology 2023One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to... (Review)
Review
One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to decidual stromal cells (DSCs), as well as the recruitment and education of decidual immune cells (DICs). At the maternal-fetal interface, stromal cells undergo morphological and phenotypic changes and interact with trophoblasts and DICs to provide an appropriate decidual bed and tolerogenic immune environment to maintain the survival of the semi-allogeneic fetus without causing immunological rejection. Despite classic endocrine mechanism by 17 β-estradiol and progesterone, metabolic regulations do take part in this process according to recent studies. And based on our previous research in maternal-fetal crosstalk, in this review, we elaborate mechanisms of decidualization, with a special focus on DSC profiles from aspects of metabolism and maternal-fetal tolerance to provide some new insights into endometrial decidualization in early pregnancy.
Topics: Pregnancy; Female; Humans; Decidua; Endometrium; Estradiol; Fetus; Energy Metabolism
PubMed: 37404833
DOI: 10.3389/fimmu.2023.1203719 -
Current Opinion in Immunology Feb 2022The human maternal-fetal interface is an immunologically complex environment that must balance the divergent demands of tolerance towards the developing fetus with... (Review)
Review
The human maternal-fetal interface is an immunologically complex environment that must balance the divergent demands of tolerance towards the developing fetus with anti-pathogen defense. The innate immune responses at the maternal-fetal interface that function in anti-microbial defense have been understudied to-date and how 'TORCH' pathogens evade maternal innate immunity to infect the fetus remains poorly understood. Herein, we discuss how newly described decidual innate lymphoid cells and maternal placenta-associated macrophage subsets may be involved in anti-pathogen defense. Moreover, we outline recent advances in our understanding of how placental trophoblasts and fetal-derived macrophages (Hofbauer cells) function in anti-microbial defense. In summary, we highlight current gaps in knowledge and describe novel experimental models of the human decidua and placenta that are poised to advance our knowledge of innate immune defenses at the maternal-fetal interface.
Topics: Decidua; Female; Humans; Immunity, Innate; Lymphocytes; Placenta; Pregnancy; Trophoblasts
PubMed: 34768027
DOI: 10.1016/j.coi.2021.10.007 -
International Journal of Medical... 2023Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions...
Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions between trophoblast cells and decidual immune cells in RM. We downloaded single-cell RNA sequencing (scRNA-seq) datasets (GSE214607) from the Gene Expression Omnibus (GEO) datasets for further analysis using the R software. The data comprised of paired placental and decidual tissues, including those from patients diagnosed with RM and matched healthy controls. A total of 22976 cells were identified in 11 cell types, including trophoblasts, immune cells, and other cells. We divided trophoblast cells into three types and analyzed their interactions with decidual immune cells. Additionally, we re-clustered NK&T cells and macrophages, identified differentially expressed genes (DEGs), enriched their functions, and compared the cell interactions with trophoblast cells in each cell type. Our single-cell atlas of the maternal-fetal interface revealed alterations in the cellular organization of the decidua and placenta, cell type-specific transcriptome, and cell communication between immune and non-immune cells in RM, which are critical for illuminating the pathophysiology of RM.
Topics: Pregnancy; Humans; Female; Placenta; Trophoblasts; Decidua; Abortion, Habitual; Pregnancy Trimester, First
PubMed: 37575278
DOI: 10.7150/ijms.86533 -
Frontiers in Cell and Developmental... 2023
PubMed: 37860817
DOI: 10.3389/fcell.2023.1298298 -
Frontiers in Immunology 2022C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response.... (Review)
Review
C-C motif ligand 2 (CCL2), also known as monocytic chemotactic protein 1 (MCP-1), is an integral chemotactic factor which recruits macrophages for the immune response. Together with its receptors (e.g., CCR2, ACKR1, and ACKR2), they exert noticeable influences on various diseases of different systems. At the maternal-fetal interface, CCL2 is detected to be expressed in trophoblasts, decidual tissue, the myometrium, and others. Meanwhile, existing reports have determined a series of physiological regulators of CCL2, which functions in maintaining normal recruitment of immunocytes, tissue remodeling, and angiogenesis. However, abnormal levels of CCL2 have also been reported to be associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and preterm labor. In this review, we concentrate on CCL2 expression at the maternal-fetal interface, as well as its precise regulatory mechanisms and classic signaling pathways, to reveal the multidimensional aspects of CCL2 in pregnancy.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Cytokines; Decidua; Trophoblasts; Abortion, Spontaneous; Chemokine CCL2
PubMed: 36685497
DOI: 10.3389/fimmu.2022.1053457 -
Journal of Reproductive Immunology Feb 2021A successful pregnancy requires that the maternal immune system recognizes and tolerates the semi-allogeneic fetus without compromising the capability of protecting both... (Review)
Review
A successful pregnancy requires that the maternal immune system recognizes and tolerates the semi-allogeneic fetus without compromising the capability of protecting both mother and fetus from various pathogens. Decidual macrophages present unique phenotypes to play a key role in the establishment of the immunological aspects of maternal-fetal interaction. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia, recurrent spontaneous miscarriage, preterm labor and fetal growth restriction. Here, we reviewed the latest knowledge on the origin, differentiation, unique phenotype and function of macrophages in normal pregnancy and in pregnancy complications. We mainly focused on the significant roles of decidual macrophages in the process of extravillous trophoblast invasion, spiral arterial remodeling, decidual stromal cells cultivation and immune tolerance maintenance in normal pregnancy, and their pathological roles in pregnancy-related complications, offering more integrated information in maternal-fetal immunity.
Topics: Decidua; Female; Histocompatibility, Maternal-Fetal; Humans; Immune Tolerance; Macrophages; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 33360717
DOI: 10.1016/j.jri.2020.103264 -
Annual Review of Immunology Apr 2023The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth... (Review)
Review
The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth century, but it was not until 1990 that these cells were identified as a type of natural killer (NK) cell. From the outset, uterine NK (uNK) cells were found to be less cytotoxic than their circulating counterparts, peripheral NK (pNK) cells. Recently, unbiased approaches have defined three subpopulations of uNK cells, all of which cluster separately from pNK cells. Here, we review the history of research into uNK cells, including their ability to interact with placental extravillous trophoblast cells and their potential role in regulating placental implantation. We go on to review more recent advances that focus on uNK cell development and heterogeneity and their potential to defend against infection and to mediate memory effects. Finally, we consider how a better understanding of these cells could be leveraged in the future to improve outcomes of pregnancy for mothers and babies.
Topics: Humans; Pregnancy; Female; Animals; Placenta; Uterus; Killer Cells, Natural; Mucous Membrane; Decidua
PubMed: 36630598
DOI: 10.1146/annurev-immunol-102119-075119 -
American Journal of Reproductive... Sep 2019The maternal-fetal interface represents a unique immune privileged site that maintains the ability to defend against pathogens while orchestrating the necessary tissue... (Review)
Review
The maternal-fetal interface represents a unique immune privileged site that maintains the ability to defend against pathogens while orchestrating the necessary tissue remodeling required for placentation. The recent discovery of novel cellular families (innate lymphoid cells, tissue-resident NK cells) suggests that our understanding of the decidual immunome is incomplete. To understand this complex milieu, new technological developments allow reproductive immunologists to collect increasingly complex data at a cellular resolution. Polychromatic flow cytometry allows for greater resolution in the identification of novel cell types by surface and intracellular protein. Single-cell RNA-seq coupled with microfluidics allows for efficient cellular transcriptomics. The extreme dimensionality and size of data sets generated, however, requires the application of novel computational approaches for unbiased analysis. There are now multiple dimensionality reduction (tSNE, SPADE) and visualization tools (SPICE) that allow researchers to efficiently analyze flow cytometry data. Development of computational tools has also been extended to RNA-seq data (including scRNA-seq), which requires specific analytical tools. Here, we provide an overview and a brief primer for the reproductive immunology community on data acquisition and computational tools for the analysis of complex flow cytometry and RNA-seq data.
Topics: Decidua; Female; Flow Cytometry; Gene Expression Profiling; Humans; Placentation; Pregnancy; RNA-Seq; Reproductive Medicine; Single-Cell Analysis
PubMed: 31206899
DOI: 10.1111/aji.13157