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The Journal of Maternal-fetal &... May 2019The present paper intends in the first place to clarify the confusing terminology for describing the vascular pathology of the placental bed in relation to long-term... (Review)
Review
AIM
The present paper intends in the first place to clarify the confusing terminology for describing the vascular pathology of the placental bed in relation to long-term risk of cardiovascular disease.
METHODS
Systematic review of relevant topics.
RESULTS
The maternal blood supply to the placenta is achieved by some 100 utero-placental spiral arteries with an outside diameter varying between 200 and 600 microns. Defective physiological changes of the myometrial segment of utero-placental spiral arteries and, particularly in preeclampsia associated to hypertensive disease, the presence of atherosclerosis in their proximal segment are a cause of obstructive vascular pathology. On the other hand, basal arteries which supply the inner myometrium and basal decidua are not affected by physiological change and maintain their musculoelastic structure. They can be identified by their external diameter of less than 120 microns. Acute atherosis is an aspecific vascular lesion that occurs in basal as well as spiral arteries inside, as well as outside, the placental bed in association with a variety of obstetrical conditions.
CONCLUSIONS
An increased risk of future cardiovascular disease, should be linked to atherosis or, at a later stage, atherosclerosis of utero-placental spiral arteries, rather than to that of decidual basal arteries.
Topics: Atherosclerosis; Decidua; Female; Humans; Longitudinal Studies; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular; Risk Factors; Uterine Artery
PubMed: 29172831
DOI: 10.1080/14767058.2017.1409718 -
Reproductive Sciences (Thousand Oaks,... Dec 2021Current methods of early diagnosis and prevention of pre-eclampsia (PE) are limited; the only available definite treatment is the initiation of delivery and complete...
Current methods of early diagnosis and prevention of pre-eclampsia (PE) are limited; the only available definite treatment is the initiation of delivery and complete removal of the placenta. Inappropriate activation of the immune system is thought to play considerable roles in PE. T cell immunoglobulin mucin-3 (Tim-3) has been reported to regulate immune responses and play important roles in maternal-fetal tolerance during early pregnancy. In this study, we investigated the functional regulation of Tim-3 in the maternal-fetal crosstalk during 3rd-trimester healthy pregnancy and its possible role in the pathogenesis of PE. We found that Tim-3 expression on decidual immune cells was associated with production of anti-inflammatory cytokines. Tim-3 pathway blockade resulted in higher IFN-γ but lower IL-4 and IL-10 production. Using a tube formation assay between HTR8/SVneo cells and human umbilical vein endothelial cells, we found that Tim-3 pathway blockade inhibits tube formation and reversed by addition of recombinant IL-4 and/or IL-10. Pre-eclamptic patients showed reduced Tim-3 expression on both decidual and peripheral immune cells (especially on peripheral CD8T cells). Therefore, we proposed that abnormal Tim-3 signal resulted in immunological imbalance at the maternal-fetal interface and may be involved in the progress of PE by affecting uterine spiral artery remodeling. Our study expanded the regulatory function of Tim-3 signaling pathway to the 3rd-trimester pregnancy and provided a new target for early warning and therapeutic strategies of PE.
Topics: Adult; Cells, Cultured; Decidua; Female; Fetal Blood; Hepatitis A Virus Cellular Receptor 2; Human Umbilical Vein Endothelial Cells; Humans; Pre-Eclampsia; Pregnancy; Signal Transduction
PubMed: 34231168
DOI: 10.1007/s43032-021-00675-3 -
Reproduction (Cambridge, England) Apr 2020Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective... (Review)
Review
Decidualization denotes the reprogramming of endometrial stromal cells that includes the secretion of different mediators like cytokines, chemokines, and the selective recruitment of immune cells. This physiological process involves changes in the secretome of the endometrial stromal cells leading to the production of immunomodulatory factors. The increased amount of protein secretion is associated with a physiological endoplasmic reticulum (ER) stress and the resulting unfolded protein response (UPR), allowing the expansion of ER and the machinery to assist the protein folding. Notably, the signaling pathways involved in the ER stress and the UPR are interconnected with the onset of a sterile inflammatory response, as well as with angiogenesis. Both of these processes have a key role in decidualization and placentation, therefore, alterations in them could lead to pregnancy complications. In this review, we will discuss how the induction of ER stress and the UPR processes that accompanies the decidualization are associated with embryo implantation and whether they might condition pregnancy outcome. The ER stress activates/triggers sensing proteins which, among others, induces kinase/RNAse-TXNIP expression, activating the NLRP3 inflammasome. This multiprotein system allows caspase-1 activation, which catalyzes the cleavage of the inactive IL-1β proform toward the mature secretory form, with pro-implantatory effects. However, the sterile inflammatory response should be later controlled in favor of a tolerogenic microenvironment to sustain pregnancy. In accordance, alterations of the ER stress and UPR processes can be reflected in recurrent implantation failures (RIF), recurrent pregnancy loss (RPL), or complications associated with deficient placentation, such as preeclampsia (PE).
Topics: Decidua; Embryo Implantation; Endoplasmic Reticulum Stress; Female; Humans; Interleukin-1; Menstrual Cycle; MicroRNAs; Unfolded Protein Response
PubMed: 31990665
DOI: 10.1530/REP-19-0391 -
Frontiers in Immunology 2021Decidual natural killer (dNK) cells are the tissue-resident and major subpopulation of NK cells at the maternal-fetal interface. It has been demonstrated that dNK cells... (Review)
Review
Decidual natural killer (dNK) cells are the tissue-resident and major subpopulation of NK cells at the maternal-fetal interface. It has been demonstrated that dNK cells play pivotal roles in pregnancy, including keeping maternal-fetal immune tolerance, promoting extravillous trophoblast (EVT) cell invasion, and driving uterine spiral artery remodeling. However, the molecular mechanisms haven't been elucidated until recent years. In this review, we systemically introduce the generation, subsets, and surface or soluble molecules of dNK cells, which are critical for maintaining the functions of dNK cells. Further, new functions of dNK cells including well-controlled cytotoxicity, immunosurveillance and immunotrophism supporting the cell-cell interaction between dNK cells and EVT cells are mainly focused. The molecular mechanisms involved in these functions are also illustrated. Moreover, pregnancy-associated diseases caused by the dNK cells abnormalities are discussed. It will be important for future investigations about the mechanism of maintenance of pregnancy and parturition and potential clinical applications of dNK cells.
Topics: Biomarkers; Cell Communication; Cytokines; Decidua; Disease Susceptibility; Female; Humans; Immune Tolerance; Immunophenotyping; Killer Cells, Natural; Maternal-Fetal Exchange; Placenta; Pregnancy; Pregnancy Trimester, First; Trophoblasts
PubMed: 34054831
DOI: 10.3389/fimmu.2021.663660 -
Frontiers in Immunology 2019The hallmark of human early pregnancy is the accumulation of a unique population of Natural Killer (dNK) cells at the main maternal-fetal interface, the . dNK cells play... (Review)
Review
The hallmark of human early pregnancy is the accumulation of a unique population of Natural Killer (dNK) cells at the main maternal-fetal interface, the . dNK cells play a crucial role in successful placentation probably by orchestrating the invasion of trophoblast cells deep into the and remodeling of the maternal spiral arteries. Recent advances in the field emphasize the importance of the local microenvironment in shaping both the phenotype and the effector functions of these innate lymphoid cells. Despite slow progress in the field, studies revealed that dNK cells sense and destroy infected cells in order to protect the fetus from invading pathogens. In this review, we will discuss key features of dNK cells during healthy pregnancy as well as their functional adaptations in limiting pathogen dissemination to the growing conceptus. The challenge is to better understand the plasticity of dNK cells in the maternal-fetal interface. Such insights would enable greater understanding of the pathogenesis in congenital infections and pregnancy disorders.
Topics: Animals; Decidua; Female; Humans; Killer Cells, Natural; Pregnancy; Virus Diseases
PubMed: 31379803
DOI: 10.3389/fimmu.2019.01397 -
Journal of Reproductive Immunology Feb 2021Pregnancy Zone Protein (PZP) is an immunosuppressive protein that is expressed by the placenta and has also been identified in immune cells. When PZP and Glycodelin A... (Observational Study)
Observational Study
BACKGROUND
Pregnancy Zone Protein (PZP) is an immunosuppressive protein that is expressed by the placenta and has also been identified in immune cells. When PZP and Glycodelin A (GdA) are combined, they act synergistically to inhibit Th-1 immune response. Little is known about its combined expression and role in normal and disturbed first trimester pregnancy.
PATIENTS AND METHODS
We investigated the expression of PZP and GdA in placental tissue obtained from spontaneous miscarriage (SM) (n = 19) and recurrent miscarriage (RM) (n = 17) at gestational weeks 6-13 by immunohistochemistry and on mRNA-level by either TaqMan PCR or in situ hybridization. Placental tissue from legal terminations of healthy pregnancies (n = 15) served as control group. Immunofluorescence double staining was used to analyse the combined expression of PZP and GdA in decidual tissue.
RESULTS
The protein level of PZP was significantly increased in decidual stroma of SM samples compared to the decidua of control specimens and also significantly upregulated in the decidual stroma cells in the RM group. Concerning GdA, the decidual stroma revealed a significantly decreased protein level in the group with spontaneous abortions than in the group with healthy pregnancies. There was also a significant downregulation of GdA in the decidual stroma of RM samples compared to the control group. We observed a significant negative correlation of PZP and GdA in decidual stromal tissue of recurrent abortion. We could confirm the staining results for PZP as well as for GdA on mRNA level. Both proteins are co-localized in decidual stroma as analysed by immunofluorescence double staining.
CONCLUSION
A balanced expression of GdA and its carrier protein PZP in the decidua seems crucial for a successful ongoing pregnancy. According to our data, these immunosuppressive proteins are co-localized in the decidual tissue and show a negative correlation only in patients suffering from recurrent abortion.
Topics: Abortion, Habitual; Adult; Decidua; Down-Regulation; Female; Glycodelin; Humans; Pregnancy; Pregnancy Proteins; Pregnancy Trimester, First; Th1 Cells; Up-Regulation; Young Adult
PubMed: 33388716
DOI: 10.1016/j.jri.2020.103267 -
Veterinary Pathology Nov 2016The decidua is the superficial portion of endometrium that transforms, or decidualizes, under the influence of progesterone to nourish the early embryo during pregnancy....
The decidua is the superficial portion of endometrium that transforms, or decidualizes, under the influence of progesterone to nourish the early embryo during pregnancy. Deciduae outside the uterus are found in nearly 100% of human pregnancies. This condition, known as deciduosis, may mimic malignancy, resulting in additional diagnostic procedures that place the mother, baby, or both at risk. Deciduosis has been described in both Old World and New World nonhuman primates in conjunction with pregnancy and after treatment with exogenous progestins. Here the authors present 6 cases of deciduosis associated with endometriotic lesions in female rhesus and cynomolgus macaques (Macaca mulatta and Macaca fascicularis). Full diagnostic necropsies with histologic analyses were performed on all animals. Deciduae were stained with hematoxylin and eosin and by immunohistochemistry for vimentin, CD10, progesterone receptor, estrogen receptor, desmin, cytokeratin, kermix P8, chorionic gonadotropin, human placental lactogen, and calretinin. The most common clinical signs were abdominal pain (4 of 6) and anorexia (2 of 6). At necropsy, macaque uteri were often enlarged or disfigured (4 of 6) with abundant fibrous adhesions (5 of 6). Affected tissue consisted of epithelial-lined cysts and decidualized stroma with scattered gamma/delta T cells. Decidualized stromal cells were large and polyhedral with abundant cytoplasm and round vesicular nuclei. They stained positive for vimentin, CD10, progesterone, and estrogen. In summary, these cases illustrate deciduosis in 6 nonhuman primates with endometriosis. Understanding decidualization in nonhuman primates will aid in elucidating the pathophysiology of deciduosis during pregnancy or endometriosis and potentially lead to new interventions.
Topics: Animals; Decidua; Endometriosis; Endometrium; Female; Macaca fascicularis; Macaca mulatta; Monkey Diseases
PubMed: 27281017
DOI: 10.1177/0300985816646433 -
The Journal of Obstetrics and... Jul 2020To compare early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE) and provide insight into the pathophysiology of pre-eclampsia (PE).
AIM
To compare early-onset pre-eclampsia (EOPE) and late-onset pre-eclampsia (LOPE) and provide insight into the pathophysiology of pre-eclampsia (PE).
METHODS
Our recent work compared the transcriptomics in decidua of EOPE, LOPE and normal pregnancies (NP).
RESULTS
We found there are a significant number of genes uniquely expressed in the decidua of EOPE and LOPE comparing with NP. Moreover, EOPE and LOPE have their distinct profiles. Unique EOPE-associated genes were mainly involved in apoptosis related pathways such as 'apoptosis' and 'Ras signaling pathway'. PIK3CB and BCL-2 are the core regulatory genes in EOPE decidua, their abnormal expression caused decidual abnormal apoptosis which is relevant to the pathogenesis of EOPE. Whereas, LOPE is a more complicated entity which has more special LOPE-associated genes involved in decidua differentiation, especially in 'gap junction pathway', 'vascular smooth muscle contraction' and 'long-term depression'. PIK3CB, FLT1, CBLC and ITGA7 are the core regulatory genes differentially expressed in EOPE decidua comparing with LOPE.
CONCLUSION
In brief, the different decidual transcriptomics of EOPE and LOPE may correlate with their different etiology. These findings highlight the complex pathophysiology of PE and provide potential targets for a new treatment strategy in patients with PE.
Topics: Decidua; Female; Humans; Pre-Eclampsia; Pregnancy
PubMed: 32281216
DOI: 10.1111/jog.14257 -
Molecular Human Reproduction Jun 2023Human endometrial stromal cells (hESCs) undergo a differentiation process with dramatic changes in cell functions during the menstrual cycle, which is called... (Review)
Review
Human endometrial stromal cells (hESCs) undergo a differentiation process with dramatic changes in cell functions during the menstrual cycle, which is called decidualization. This is an important event for implantation of the embryo and successful pregnancy. Defective decidualization can cause implantation failure, miscarriage, and unexplained infertility. A number of genes are upregulated or downregulated during decidualization. Recent studies have shown that epigenetic mechanisms are involved in the regulation of decidualization-related genes and that histone modifications occur throughout the genome during decidualization. The present review focuses on the involvement of genome-wide histone modifications in dramatic changes in gene expression during decidualization. The main histone modifications are the increases of H3K27ac and H3K4me3, which activate transcription. C/EBPβ works as a pioneer factor throughout the genome by recruiting p300. This is the main cause of the genome-wide acetylation of H3K27 during decidualization. Histone modifications were observed in both the proximal promoter and distal enhancer regions. Genome editing experiments show that the distal regions have transcriptional activities, which suggests that decidualization induces the interactions between proximal promoter and distal enhancer regions. Taken together, these findings show that gene regulation during decidualization is closely associated with genome-wide changes of histone modifications. This review provides new insights regarding the cases of implantation failure in terms of decidualization insufficiency owing to epigenetic dysregulation, and may lead to novel treatment options for women with implantation failure.
Topics: Pregnancy; Humans; Female; Endometrium; Decidua; Histone Code; Gene Expression; Stromal Cells
PubMed: 37310913
DOI: 10.1093/molehr/gaad019 -
Archives of Gynecology and Obstetrics Sep 2023Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases...
PURPOSE
Miscarriage is one of the most common complications of pregnancy. Although chromosomal abnormalities of the embryo is a well-known cause of miscarriage, a lot of cases remain unexplained, with immunologic and vascular growth alterations being considered as probable causes. Chemokines are produced by a variety of cells and exhibit several functions including both pro and anti-angiogenic properties. In this study, we investigated the role of the angiogenic and angiostatic chemokines in placenta and decidua tissues from spontaneous and induced abortions.
METHODS
Total RNA was extracted from the placenta and decidua tissues, which was then purified and converted into cDNA. Real-time PCR was then performed for the expression of the angiogenic CCL2, CCL5, CCL20, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8 and CXCL4, and the angiostatic CXCL9, CXCL10, CXCL11, CXCL12 and CXCL14 and results were then statistically analyzed.
RESULTS
Regarding the placenta, CXCL7 (2.29-fold, 2.16-2.38, p < 0.05), CXCL4 (1.01-fold, 0.74-4.447, p < 0.05), CXCL9 (0.87-fold, 0.43-1.34, p < 0.05) and CXCL11 (0.31-fold, 0.22-0.45, p < 0.05) were altered in spontaneous abortions. CCL2, CCL5, CXCL2-3, CXCL8, CXCL10, CXCL12 and CXCL14 were not statistically significant altered. Regarding the decidua, CXCL7 (7.13-fold, 6.32-7.54, p < 0.01), CXCL8 (11.02-fold, 8.58-13.45, p < 0.05), CCL20 (1.21-fold, 0.29-1.89, p < 0.05) and CXCL9 (5.49-fold, 3.67-6.39, p < 0.05) were overexpressed in spontaneous abortions. CXCL2-4, CCL2, CCL5, CXCL10-12 and CXCL14 did not show any differences. The expression of the chemokines CXCL1, CXCL5-6 was absent in either tissue or group.
CONCLUSION
Our results show that the overexpression of angiostatic and diminished expression of angiogenic chemokines takes place in the placenta and decidua of spontaneous abortions, suggesting that dysregulation of angiogenesis could be a contributive factor to the pathogenesis of miscarriage.
Topics: Pregnancy; Female; Humans; Abortion, Spontaneous; Placenta; Decidua
PubMed: 35997970
DOI: 10.1007/s00404-022-06725-8