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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 -
Environmental Research Jul 2023Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the...
Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the outer is in direct contact with maternal blood (decidua placenta), and the inner (villi) directly in contact with the fetus. Environmental contaminants, such as per- and polyfluoroalkyl substances (PFAS) also demonstrated the ability to cross the tissue multiple layers, posing at risk the health of the fetus. The aim of the present study was to analyse the PFAS amount in decidua and villi placenta explants and to study differences in their distribution among the two side of this organ. The determination of 23 PFAS was carried out by liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM). Our research included women who delivered at term between 2021 and 2022. Our data indicated that all samples contained at least one PFAS, demonstrating the ubiquitarian presence of these compounds in our population. A high occurrence of PFOS, PFOA and PFHxS, followed by PFHxA, PFBS and PFUnA was found. The fluorotelomer 6:2 FTS was also present in more than 40% of samples and this represent the first data on placenta explants. Mean and median PFAS values for decidual explants were 0.5 ng/g and 0.4 ng/g (SD 0.3), while for villi explants mean and median values were 0.6 ng/g and 0.4 ng/g (SD 0.4). A different pattern of accumulation was observed between villi and decidual explants for PFOS, PFOA and PFUnA (villi > decidua) and PFHxA, PFHxS, PFBS and 6:2 FTS (decidua > villi). Even if the mechanism of this selectively accumuation is not yet understood, molecular degree of ionization and its lipophilicity could at least in part explain this difference. This study expands the limited data describing PFAS levels in the placenta and pose attention on PFAS exposure during pregnancy.
Topics: Pregnancy; Humans; Female; Placenta; Fluorocarbons; Mothers; Decidua; Alkanesulfonic Acids; Environmental Pollutants
PubMed: 37119845
DOI: 10.1016/j.envres.2023.115955 -
Frontiers in Immunology 2022The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This...
The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.
Topics: Decidua; Female; Flow Cytometry; Humans; Infant, Newborn; Labor, Obstetric; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 35757768
DOI: 10.3389/fimmu.2022.877314 -
Nature Reviews. Immunology Apr 2023The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the... (Review)
Review
The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the first few weeks of human pregnancy, because this is the site at which maternal leukocytes initially interact with and can recognize fetal trophoblast cells, potentially involving allorecognition by both T cells and natural killer (NK) cells. NK cells are the dominant leukocyte population in first-trimester decidua, and genetic studies point to a role of allorecognition by uterine NK cells in establishing a boundary between the mother and the fetus. By contrast, definitive evidence that allorecognition by decidual T cells occurs during the first trimester is lacking. Thus, our view is that during the crucial period when the placenta is established, damaging T cell-mediated adaptive immune responses towards placental trophoblast are minimized, whereas NK cell allorecognition contributes to successful implantation and healthy pregnancy.
Topics: Pregnancy; Humans; Female; Trophoblasts; Placenta; Decidua; Pregnancy Trimester, First; Killer Cells, Natural
PubMed: 36192648
DOI: 10.1038/s41577-022-00777-2 -
Communications Biology May 2023Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival,...
Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purβ. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purβ, and highlight the clinical implications of these mechanisms in the pathology of RSA.
Topics: Pregnancy; Female; Humans; Endometrium; Decidua; Abortion, Habitual; Stromal Cells; DNA-Binding Proteins; Co-Repressor Proteins; Cell Cycle Proteins
PubMed: 37244968
DOI: 10.1038/s42003-023-04931-x -
Medicine International 2024Subchorionic hematoma (SCH) is a hematoma in which blood accumulates between the chorion and decidua basalis due to the separation of the chorion and decidua basalis. It... (Review)
Review
Subchorionic hematoma (SCH) is a hematoma in which blood accumulates between the chorion and decidua basalis due to the separation of the chorion and decidua basalis. It is common in patients with threatened abortion in early pregnancy and is mainly detected by ultrasound. SCH mainly manifests as an hypoechoic or anechoic crescent-shaped fluid dark area on ultrasound images. Although there are numerous studies on SCH, its pathogenesis and etiology remain unclear, and its influence on pregnancy outcomes is also controversial; there are also no uniform clinical treatment guidelines. Current studies suggest that the occurrence of SCH may be related to several factors, such as abnormal coagulation function, autoimmune factors of pregnant women, assisted reproduction, drug use during pregnancy and reproductive tract infection; however, its exact etiology remains unclear. Some studies suggest that SCH is associated with adverse pregnancy outcomes such as miscarriage, preterm birth, preeclampsia and fetal growth restriction, although other studies have found that SCH does not increase the risk of adverse pregnancy outcomes. Therefore, the present review mainly discusses the pathogenesis, etiology and treatment of SCH in an aim to provide a reference for the clinical treatment of this condition in pregnant women.
PubMed: 38362561
DOI: 10.3892/mi.2024.134 -
Human Immunology May 2021The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems... (Review)
Review
The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems must favor acceptance of the fetal allograft. Macrophages are the second most abundant immune cells after natural killer (NK) cells in the decidua. In coordination with decidual NK cells and dendritic cells, macrophages aid in implantation, vascular remodeling, placental development, immune tolerance to placental cells, and maintenance of tissue homeostasis at the maternal-fetal interface. Decidual macrophages show the classical activated (M1) and alternatively activated (M2) phenotypes under the influence of the local milieu of growth factors and cytokines, and appropriate temporal regulation of the M1/M2 switch is vital for successful pregnancy. Disturbances in the mechanisms that control the M1/M2 balance and associated functions during pregnancy can trigger a spectrum of pregnancy complications ranging from preeclampsia and fetal growth restriction to preterm delivery. This review addresses various mechanisms of tolerance, focusing on the basic biology of macrophages, their plasticity and polarization, and their protective roles at the immune-privileged maternal-fetal interface, including direct and indirect roles in promoting fetomaternal immune tolerance.
Topics: Animals; Decidua; Female; Histocompatibility, Maternal-Fetal; Humans; Immune Tolerance; Macrophages; Pregnancy; Pregnancy Complications; Th1-Th2 Balance
PubMed: 33715911
DOI: 10.1016/j.humimm.2021.02.013 -
Molecular Human Reproduction Apr 2023Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes...
Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are primarily governed by the steroid hormones estrogen (E2) and progesterone (P4) but can also be influenced by extrinsic factors from the stroma. Using a human endometrial epithelial organoid system, transcriptome and proteome analyses identified distinct responses of the organoids to steroid hormones and prostaglandin E2 (PGE2). Notably, P4 and PGE2 modulated the basolateral secretion of organoid proteins, particularly cystatin C (CST3), serpin family A member 3 (SERPINA3), and stanniocalcin 1 (STC1). CST3, but not SERPINA3 or STC1, attenuated the in vitro stromal decidualization response to steroid hormones and PGE2. These findings provide evidence that uterine gland-derived factors impact stromal cell decidualization, which has implications for pregnancy establishment and fertility in women.
Topics: Humans; Pregnancy; Female; Dinoprostone; Placenta; Endometrium; Embryo Implantation; Progesterone; Stromal Cells; Decidua
PubMed: 36821428
DOI: 10.1093/molehr/gaad007 -
Frontiers in Immunology 2023The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment... (Review)
Review
The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.
Topics: Pregnancy; Female; Humans; Prolactin; Decidua; Placenta; Extraembryonic Membranes; Amniotic Fluid
PubMed: 37359537
DOI: 10.3389/fimmu.2023.1212736