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Current Issues in Molecular Biology Nov 2021Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as...
Cyclic changes, such as growth, decidualization, shedding, and regeneration, in the human endometrium are regulated by the reciprocal action of female hormones, such as estradiol (E), and progesterone (P). Matrix metalloproteases (MMPs) and tissue inhibitors of MMPs (TIMPs) control the invasion of extravillous trophoblast cells after implantation. Several MMPs and TIMPs function in the decidua and endometrial stromal cells (ESCs). Here, we aimed to systematically investigate the changes in MMPs and TIMPs associated with ESC decidualization. We evaluated the expression of 23 MMPs, four TIMPs, and four anti-sense non-coding RNAs from MMP loci. Primary ESC cultures treated with E + medroxyprogesterone acetate (MPA), a potent P receptor agonist, showed significant down-regulation of , , , , , and in decidualized ESCs, as assessed by quantitative reverse transcription PCR. Further, and were significantly upregulated in decidualized ESCs. siRNA-mediated silencing of Heart and Neural Crest Derivatives Expressed 2 (HAND2), a master transcriptional regulator in ESC decidualization, significantly increased expression in untreated human ESCs. These results collectively indicate the importance of and in ESC decidualization and highlight the role of HAND2 in repressing transcription, thereby regulating decidualization.
Topics: Adult; Biomarkers; Cells, Cultured; Decidua; Endometrium; Female; Gene Expression Regulation; Humans; Matrix Metalloproteinases; Middle Aged; Steroids; Stromal Cells; Tissue Inhibitor of Metalloproteinases; Young Adult
PubMed: 34940120
DOI: 10.3390/cimb43030146 -
Human Reproduction Update Jul 2012During pregnancy, maternal uterine spiral arteries (SAs) are remodelled from minimal-flow, high-resistance vessels into larger diameter vessels with low resistance and... (Review)
Review
BACKGROUND
During pregnancy, maternal uterine spiral arteries (SAs) are remodelled from minimal-flow, high-resistance vessels into larger diameter vessels with low resistance and high flow. Fetal extravillous trophoblasts (EVT) have important roles in this process. Decidual natural killer cells (dNK cells) are the major maternal immune component of the decidua and accumulate around SAs before trophoblast invasion. A role for dNK cells in vessel remodelling is beginning to be elucidated. This review examines the overlapping and dissimilar mechanisms used by EVT and dNK cells in this process and how this may mirror another example of tissue remodelling, namely cancer development.
METHODS
The published literature was searched using Pubmed focusing on EVT, dNK cells and SA remodelling. Additional papers discussing cancer development are also included.
RESULTS
Similarities exist between actions carried out by dNK cells and EVT. Both interact with vascular cells lining the SA, as well as with each other, to promote transformation of the SA. EVT differentiation has previously been likened to the epithelial-mesenchymal transition in cancer cells, and we discuss how dNK-EVT interactions at the maternal-fetal interface can also be compared with the roles of immune cells in cancer.
CONCLUSIONS
The combined role that dNK cells and EVT play in SA remodelling suggests that these interactions could be described as a partnership. The investigation of pregnancy as a multicellular system involving both fetal and maternal components, as well as comparisons to similar examples of tissue remodelling, will further identify the key mechanisms in SA remodelling that are required for a successful pregnancy.
Topics: Cell Differentiation; Decidua; Epithelial-Mesenchymal Transition; Female; Humans; Killer Cells, Natural; Pregnancy; Trophoblasts; Uterine Artery
PubMed: 22523109
DOI: 10.1093/humupd/dms015 -
PloS One 2018It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the...
It is increasingly evident that cytokines and growth factors produced in the decidua play a pivotal role in the regulation of the local immune microenvironment and the establishment of pregnancy. One of the major growth factors produced in the decidua is vascular endothelial growth factor (VEGF), which acts not only on endothelial cells, but also on multiple other cell types, including macrophages. We sought to determine whether decidua-derived VEGF affects macrophage recruitment and polarization using human endometrial/decidual tissue samples, primary human endometrial stromal cells (ESCs), and the human monocyte cell line THP1. In situ hybridization was used for assessment of local VEGF expression and immunohistochemistry was used for identification and localization of CD68-positive endometrial macrophages. Macrophage migration in culture was assessed using a transwell migration assay, and the various M1/M2 phenotypic markers and VEGF expression were assessed using quantitative real-time PCR (qRT-PCR). We found dramatic increases in both VEGF levels and macrophage numbers in the decidua during early pregnancy compared to the secretory phase endometrium (non-pregnant), with a significant increase in M2 macrophage markers, suggesting that M2 is the predominant macrophage phenotype in the decidua. However, decidual samples from preeclamptic pregnancies showed a significant shift in macrophage phenotype markers, with upregulation of M1 and downregulation of M2 markers. In THP1 cultures, VEGF treatment significantly enhanced macrophage migration and induced M1 macrophages to shift to an M2 phenotype. Moreover, treatment with conditioned media from decidualized ESCs induced changes in macrophage migration and polarization similar to that of VEGF treatment. These effects were abrogated by the addition of a potent VEGF inhibitor. Together these results suggest that decidual VEGF plays a significant role in macrophage recruitment and M2 polarization, and that inhibition of VEGF signaling may contribute to the shift in macrophage polarity observed in different pregnancy disorders, including preeclampsia.
Topics: Adult; Cell Line; Cell Polarity; Decidua; Female; Humans; Macrophages; Real-Time Polymerase Chain Reaction; Vascular Endothelial Growth Factor A
PubMed: 29324807
DOI: 10.1371/journal.pone.0191040 -
Proceedings. Biological Sciences Apr 2023The placenta has evolved to support the development of the embryo and fetus during the different intrauterine periods of life. By necessity, its development must precede...
The placenta has evolved to support the development of the embryo and fetus during the different intrauterine periods of life. By necessity, its development must precede that of the embryo. There is now evidence that during embryogenesis and organogenesis, the development of the human placenta is supported by histotrophic nutrition secreted from endometrial glands rather than maternal blood. These secretions provide a plentiful supply of glucose, lipids, glycoproteins and growth factors that stimulate rapid proliferation and differentiation of the villous trophoblast. Furthermore, evidence from endometrial gland organoids indicates that expression and secretion of these products are upregulated following sequential exposure to oestrogen, progesterone and trophoblastic and decidual hormones, in particular prolactin. Hence, a feed-forward signalling dialogue is proposed among the trophoblast, decidua and glands that enables the placenta to stimulate its own development, independent of that of the embryo. Many common complications of pregnancy represent a spectrum of disorders associated with deficient trophoblast proliferation. Increasing evidence suggests that this spectrum is mirrored by one of impaired decidualization, potentially compromising histotroph secretion through diminished prolactin secretion and reduced gland function. Optimizing endometrial wellbeing prior to conception may therefore help to prevent common pregnancy complications, such as miscarriage, growth restriction and pre-eclampsia.
Topics: Pregnancy; Female; Humans; Decidua; Prolactin; Placenta; Endometrium; Trophoblasts
PubMed: 37072047
DOI: 10.1098/rspb.2023.0191 -
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 -
The Yale Journal of Biology and Medicine Mar 2012The semi-allogeneic fetus, whose genome consists of maternally and paternally inherited alleles, must coexist with an active maternal immune system during its 9 months... (Review)
Review
The semi-allogeneic fetus, whose genome consists of maternally and paternally inherited alleles, must coexist with an active maternal immune system during its 9 months in utero. Macrophages are the second most abundant immune cell at the maternal-fetal interface, although populations and functions for these populations remain ill defined. We have previously reported two distinct subsets of CD14(+) decidual macrophages found to be present in first trimester decidual tissue, 20 percent CD11c(HI) and 68 percent CD11c(LO). Interestingly, CD11c(HI) decidual macrophages express genes associated with lipid metabolism, inflammation, and antigen presentation function and specifically upregulate CD1 molecules. Conversely, CD11c(LO) decidual macrophages express genes associated with extracellular matrix formation, muscle regulation, and tissue growth. The large abundance of CD11c(HI) decidual macrophages and their ability to process antigens more efficiently than CD11c(LO) macrophages suggests that CD11c(HI) macrophages may be important antigen processing and presenting cells at the maternal-fetal interface, while CD11c(LO) macrophages may perform necessary homeostatic functions during placental construction. Thus, macrophage heterogeneity may be an important and necessary division of labor that leads to both an induction of maternal immune cell tolerance to fetal antigens as well as basic homeostatic functions in human pregnancy.
Topics: Antigen-Presenting Cells; Decidua; Female; Humans; Killer Cells, Natural; Macrophages; Maternal-Fetal Exchange; Pregnancy; Reproduction
PubMed: 22461749
DOI: No ID Found -
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 -
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 -
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 -
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