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Archives of Pathology & Laboratory... Apr 2019Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of... (Review)
Review
Primary malignant deciduoid mesothelioma is a rare subtype of epithelioid mesothelioma that was first described in the peritoneum in young women without a history of asbestos exposure. It was thought to be a distinct clinicopathologic entity with ominous prognosis; recent studies have better characterized this entity. On morphology, primary malignant deciduoid mesothelioma is characterized by cytomorphologic features resembling decidualized tissue. Pleomorphism is variable. The immunoprofile is similar to other epithelioid mesotheliomas. The prognosis is the same as other epithelioid mesotheliomas and seems to depend on histological grade.
Topics: Decidua; Female; Humans; Lung Neoplasms; Mesothelioma; Mesothelioma, Malignant; Peritoneal Neoplasms
PubMed: 30500290
DOI: 10.5858/arpa.2017-0461-RS -
BMC Genomics Oct 2023Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are...
BACKGROUND
Extravillous trophoblast cell (EVT) differentiation and its communication with maternal decidua especially the leading immune cell type natural killer (NK) cell are critical events for placentation. However, appropriate in vitro modelling system and regulatory programs of these two events are still lacking. Recent trophoblast organoid (TO) has advanced the molecular and mechanistic research in placentation. Here, we firstly generated the self-renewing TO from human placental villous and differentiated it into EVTs (EVT-TO) for investigating the differentiation events. We then co-cultured EVT-TO with freshly isolated decidual NKs for further study of cell communication. TO modelling of EVT differentiation as well as EVT interaction with dNK might cast new aspect for placentation research.
RESULTS
Single-cell RNA sequencing (scRNA-seq) was applied for comprehensive characterization and molecular exploration of TOs modelling of EVT differentiation and interaction with dNKs. Multiple distinct trophoblast states and dNK subpopulations were identified, representing CTB, STB, EVT, dNK1/2/3 and dNKp. Lineage trajectory and Seurat mapping analysis identified the close resemblance of TO and EVT-TO with the human placenta characteristic. Transcription factors regulatory network analysis revealed the cell-type specific essential TFs for controlling EVT differentiation. CellphoneDB analysis predicted the ligand-receptor complexes in dNK-EVT-TO co-cultures, which relate to cytokines, immunomodulation and angiogenesis. EVT was known to affect the immune properties of dNK. Our study found out that on the other way around, dNKs could exert effects on EVT causing expression changes which are functionally important.
CONCLUSION
Our study documented a single-cell atlas for TO and its applications on EVT differentiation and communications with dNKs, and thus provide methodology and novel research cues for future study of human placentation.
Topics: Pregnancy; Female; Humans; Trophoblasts; Placenta; Decidua; Cell Differentiation; Organoids; Killer Cells, Natural; Cell Movement
PubMed: 37853336
DOI: 10.1186/s12864-023-09690-x -
Reproduction (Cambridge, England) Jul 2021Deficient decidualization of endometrial stromal cells (ESCs) can cause adverse pregnancy outcomes including miscarriage, intrauterine growth restriction, and...
Deficient decidualization of endometrial stromal cells (ESCs) can cause adverse pregnancy outcomes including miscarriage, intrauterine growth restriction, and pre-eclampsia. Decidualization is regulated by multiple factors such as hormones and circadian genes. Melatonin, a circadian-controlled hormone, is reported to be important for various reproductive processes, including oocyte maturation and placenta development. Its receptor, MT1, is considered to be related to intrauterine growth restriction and pre-eclampsia. However, the role of melatonin-MT1 signal in decidualization remains unknown. Here, we reported that decidual stromal cells from miscarriages displayed deficient decidualization with decreased MT1 expression. The expression level of MT1 is gradually increased with the process of decidualization induction in vitro. MT1 knockdown suppressed the decidualization level, while the overexpression of MT1 promoted the decidualization process. Moreover, changing MT1 level could regulate the expression of decidualization-related transcription factor FOXO1. Melatonin promoted decidualization and reversed the decidualization deficiency due to MT1 knockdown. Using in vitro and in vivo experiments, we further identified that lipopolysaccharide (LPS) could induce inflammation and decidualization resistance with downregulated MT1 expression, and melatonin could reverse the inflammation and decidualization resistance induced by LPS. These results suggested that the melatonin-MT1 signal might be essential for decidualization and might provide a novel therapeutic target for decidualization deficiency-associated pregnancy complications.
Topics: Abortion, Spontaneous; Adult; Animals; Case-Control Studies; Cells, Cultured; Decidua; Endometrium; Female; Gene Expression Regulation; Humans; Melatonin; Mice; Pregnancy; Receptor, Melatonin, MT1; Young Adult
PubMed: 34115609
DOI: 10.1530/REP-21-0159 -
Journal of Assisted Reproduction and... May 2019The common spiny mouse (Acomys cahirinus) is the only known rodent to demonstrate a myriad of physiological processes unseen in their murid relatives. The most recently... (Review)
Review
The common spiny mouse (Acomys cahirinus) is the only known rodent to demonstrate a myriad of physiological processes unseen in their murid relatives. The most recently discovered of these uncharacteristic traits: spontaneous decidual transformation of the uterus in virgin females, preceding menstruation. Menstruation occurring without experimental intervention in rodents has not been documented elsewhere to date, and natural menstruation is indeed rare in the animal kingdom outside of higher order primates. This review briefly summarises the current knowledge of spiny mouse biology and taxonomy, and explores their endocrinology which may aid in our understanding of the evolution of menstruation in this species. We propose that DHEA, synthesised by the spiny mouse (but not other rodents), humans and other menstruating primates, is integral in spontaneous decidualisation and therefore menstruation. We discuss both physiological and behavioural attributes across the menstrual cycle in the spiny mouse analogous to those observed in other menstruating species, including premenstrual syndrome. We further encourage the use of the spiny mouse as a small animal model of menstruation and female reproductive biology.
Topics: Animals; Decidua; Female; Haplorhini; Humans; Menstruation; Mice; Murinae
PubMed: 30610663
DOI: 10.1007/s10815-018-1390-3 -
Placenta Apr 2021Uteroplacental acute atherosis is frequently observed in preeclampsia, and shares features with early atherosclerotic lesions, including artery wall foam cells. The...
INTRODUCTION
Uteroplacental acute atherosis is frequently observed in preeclampsia, and shares features with early atherosclerotic lesions, including artery wall foam cells. The lipid-associated proteins FABP4 (fatty acid binding protein 4), perilipin-2, and LOX-1 (lectin-like oxidized LDL-receptor 1) are involved in atherosclerotic foam cell formation. Increased levels of these proteins have been associated with preeclampsia systemically and in placental tissue. Their role in acute atherosis is yet unidentified. Our aim was to describe the presence of these proteins in acute atherosis, and compare our findings to what is known in early atherosclerotic lesions.
METHODS
Serial sections of decidua basalis tissue from 12 normotensive (4 with acute atherosis) and 23 preeclamptic pregnancies (16 with acute atherosis) were stained with HE and immunostained for CK7, CD68, FABP4, perilipin-2, and LOX-1. Artery wall and perivascular protein expression was assessed in 190 spiral artery sections; 55 with acute atherosis.
RESULTS
Acute atherosis foam cells were commonly positive for perilipin-2 (55%), less often for FABP4 (13%), and never for LOX-1. LOX-1 was frequently observed in intramural trophoblasts of normal spiral arteries. Perivascularly, LOX-1 positivity of decidual stromal cells surrounding arteries with acute atherosis was significantly increased as compared to arteries lacking acute atherosis (38% vs. 15%, p < 0.001).
DISCUSSION
We found that perilipin-2 and FABP4 are expressed by acute atherosis foam cells, similar to atherosclerosis, supporting possible shared pathways for foam cell generation. Unlike atherosclerosis, LOX-1 is not present in acute atherosis, possibly explained by pregnancy-specific routes to decidua basalis foam cell generation.
Topics: Adult; Atherosclerosis; Decidua; Fatty Acid-Binding Proteins; Female; Foam Cells; Humans; Perilipin-2; Scavenger Receptors, Class E
PubMed: 33725567
DOI: 10.1016/j.placenta.2021.03.001 -
Frontiers in Immunology 2018Adaptive immune system, principally governed by the T cells-dendritic cells (DCs) nexus, is an essential mediator of gestational fetal tolerance and protection against...
Adaptive immune system, principally governed by the T cells-dendritic cells (DCs) nexus, is an essential mediator of gestational fetal tolerance and protection against infection. However, the exact composition and dynamics of DCs and T cell subsets in gestational tissues are not well understood. These are controlled in human physiology by a complex interplay of alloantigen distribution and presentation, cellular/humoral active and passive tolerance, hormones/chemokines/angiogenic factors and their gradients, systemic and local microbial communities. Reductive discrimination of these factors in physiology and pathology of model systems and humans requires simplification of the model and increased resolution of interrogative technologies. As a baseline, we have studied the gestational tissue dynamics in the syngeneic C57BL/6 mice, as the simplest immunological environment, and focused on validating the approach to increased data density and computational analysis pipeline afforded by highly polychromatic flow cytometry and machine learning interpretation. We mapped DC and T cell subsets, and comprehensively examined their maternal (decidual)-fetal (placental) interface dynamics. Both frequency and composition of decidual DCs changed across gestation, with a dramatic increase in myeloid DCs in early pregnancy, and exclusion of plasmacytoid DCs. CD4+ T cells, in contrast, were lower at all gestational ages and an unusual CD4CD8TCRαβgroup was prominent at mid-pregnancy. Dimensionality reduction with machine learning-aided clustering revealed that CD4CD8 T cells were phenotypically different from CD4+ and CD8+ T cells. Additionally, divergence between maternal decidual and fetal placental compartment was prominent, with absence of DCs from the placenta, but not decidua or embryo. These results provide a novel framework and a syngeneic baseline on which the specific role of alloantigen/tolerance, polymicrobial environment, and models of pregnancy pathology can be precisely modeled and analyzed.
Topics: Adaptive Immunity; Animals; Cells, Cultured; Decidua; Dendritic Cells; Female; Fetus; Gestational Age; Humans; Immune Tolerance; Male; Mice, Inbred C57BL; Placenta; Pregnancy; T-Lymphocyte Subsets; Uterus
PubMed: 30283441
DOI: 10.3389/fimmu.2018.02087 -
Autoimmunity May 2021Indoleamine 2,3-dioxygenase1(IDO1) is one of the most important proteins in protect the embryos from the mother's immune system during pregnancy. However, the regulation...
Indoleamine 2,3-dioxygenase1(IDO1) is one of the most important proteins in protect the embryos from the mother's immune system during pregnancy. However, the regulation of the protein expression at the maternal-foetal interface is not fully known. We aimed to study the regulation of IDO1 expression by progesterone in villi and decidua of in early pregnancy. Fifty cases of early pregnancy women's villi and decidua were collected. Tissue explants of chorionic villi and the decidua were cultured in media containing in different concentrations of progesterone, in the presence or absence of mifepristone. Western blot analysis and immunofluorescence were used to detect the expression of IDO1 in chorionic villi and decidua in cultured tissues. IDO1 protein was identified in chorionic villi and decidua tissues of normal pregnant women, and the expression of IDO1in the decidua was significantly higher than those in chorionic villi. Progesterone decreased IDO1 expression in early pregnancy chorionic villi and decidua, and mifepristone, as the progesterone inhibitor, reverted this effect. In normal physiological state of pregnancy, progesterone may be involved in the regulation of immune tolerance by negative regulation of IDO1 expression at maternal foetal interface. Progesterone may down-regulate IDO1 expression during early pregnancy.
Topics: Adult; Chorionic Villi; Decidua; Female; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase; Pregnancy; Progesterone
PubMed: 33792452
DOI: 10.1080/08916934.2021.1907572 -
Reproductive Sciences (Thousand Oaks,... May 2018Uterine fibroids are benign uterine smooth muscle tumors that are present in up to 8 out of 10 women by the age of 50. Many of these women experience symptoms such as... (Review)
Review
Uterine fibroids are benign uterine smooth muscle tumors that are present in up to 8 out of 10 women by the age of 50. Many of these women experience symptoms such as heavy and irregular menstrual bleeding, early pregnancy loss, and infertility. Traditionally believed to be inert masses, fibroids are now known to influence endometrial function at the molecular level. We present a comprehensive review of published studies on the effect of uterine fibroids on endometrial function. Our goal was to explore the current knowledge about how uterine fibroids interact with the endometrium and how these interactions influence clinical symptoms. Our review shows that submucosal fibroids produce a blunted decidualization response with decreased release of cytokines critical for implantation such as leukocyte inhibitory factor and cell adhesion molecules. Furthermore, fibroids alter the expression of genes relevant for implantation, such as bone morphogenetic protein receptor type II, glycodelin, among others. With regard to heavy menstrual bleeding, fibroids significantly alter the production of vasoconstrictors in the endometrium, leading to increased menstrual blood loss. Fibroids also increase the production of angiogenic factors such as basic fibroblast growth factor and reduce the production of coagulation factors resulting in heavy menses. Understanding the crosstalk between uterine fibroids and the endometrium will provide key insights into implantation and menstrual biology and drive the development of new and innovative therapeutic options for the management of symptoms in women with uterine fibroids.
Topics: Animals; Decidua; Embryo Implantation; Endometrium; Female; Humans; Leiomyoma; Uterine Neoplasms
PubMed: 28826369
DOI: 10.1177/1933719117725827 -
The Journal of Maternal-fetal &... Dec 2023Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the...
BACKGROUND AND AIM
Unexplained recurrent pregnancy loss has been a a challenging research task to experts since there is no explicit pathophysiological mechanism and therefore, the treatment remains elusive. Immunological imbalance and morphological abnormalities are under investigation. This study aims to evaluate the implication of MMP-2, MMP-9, EGFR, and IL-8 in recurrent pregnancy loss cases.
MATERIALS & METHODS
The study was carried out through comparison among two groups; the unexplained miscarriage group which consisted of 22 women, and the control group consisted of 18 women, who had electively terminated their pregnancies. Both groups were in the first trimester of gestation. The specimens included the trophoblast, decidua basalis, and decidua parietalis. The study was conducted immunohistochemical methods. Antibodies were used against MMP-2, MMP-9, EGFR, and IL-8. The results were presented at a contingency table and were statistically analyzed with the Chi-Square Test (X).
RESULTS
There were remarkable disparities in some cases in the comparison of the two groups. MMP-9 was detected significantly high in recurrent pregnancy loss (RPL) cases, both on trophoblastic and decidual specimens (-value < .00001), MMP-2 displayed no difference among the two groups (mild to moderate detection on trophoblast and almost negative on decidual tissues). EGFR was highly detected in trophoblastic tissue (-value = .014). IL-8 detection was particularly different in both trophoblast and decidua parietalis of the two groups (-value < .01).
CONCLUSION
The study revealed both morphological and immunological dysregulations that might participate in the RPL pathogenesis.
Topics: Female; Humans; Pregnancy; Abortion, Habitual; Decidua; ErbB Receptors; Interleukin-8; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Pregnancy Trimester, First; Trophoblasts
PubMed: 37258409
DOI: 10.1080/14767058.2023.2218523 -
Reproductive Biology and Endocrinology... Oct 2021The critical immune effectors, including T, B, and natural killer (NK) cells, dendritic cells, and macrophages participate in regulating immune responses during... (Review)
Review
The critical immune effectors, including T, B, and natural killer (NK) cells, dendritic cells, and macrophages participate in regulating immune responses during pregnancy. Among these immune cells, decidual NK (dNK) cells are involved in key placental development processes at the maternal-fetal interface, such as uterine spiral artery remodeling, trophoblast invasion, and decidualization. Mechanistically, dNK cells significantly influence pregnancy outcome by secreting cytokines, chemokines, and angiogenic mediators and by their interactions with trophoblasts and other decidual cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that participate in the initiation and progression of human diseases. Although the functions of circulating miRNAs in pathological mechanism has been extensively studied, the regulatory roles of miRNAs in NK cells, especially in dNK cells, have been rarely reported. In this review, we analyze the effects of miRNA regulations of dNK cell functions on the immune system during gestation. We discuss aberrant expressions of certain miRNAs in dNK cells that may lead to pathological consequences, such as recurrent pregnancy loss (RPL). Interestingly, miRNA expression patterns are also different between dNK cells and peripheral NK (pNK) cells, and pNK cells in the first- and third-trimester of gestation. The dysregulation of miRNA plays a pivotal regulatory role in driving immune functions of dNK and pNK cells. Further understanding of the molecular mechanisms of miRNAs in dNK cells may provide new insights into the development of therapeutics to prevent pregnancy failure.
Topics: Abortion, Habitual; Decidua; Female; Humans; Killer Cells, Natural; MicroRNAs; Pregnancy; Trophoblasts
PubMed: 34600537
DOI: 10.1186/s12958-021-00812-2