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BMC Pharmacology & Toxicology Jul 2022As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported...
BACKGROUND
As a progesterone receptor antagonist, mifepristone combined with misoprostol is widely used to terminate early pregnancy in clinical practice. It has also been reported that mifepristone may cause cell death in decidual cells and result in hemorrhage of the decidua and insufficient blood supply. However, little is known about the histological effects of mifepristone on human decidua and chorion.
METHODS
Histological and subcellular structural changes of decidua and chorionic villi from women taking mifepristone at early pregnancy times were examined by Hematoxylin and eosin (H&E) staining and transmission Electron microscope. The expression of apoptosis-related proteins Bax/Bcl-2 was examined by immunohistochemistry.
RESULTS
After 48 h of mifepristone administration, the decidua tissue and chorionic villus structures were altered in women within 39-49 days of gestation and displayed varying degrees of degeneration and necrosis-like features. Apoptotic events were observed in the decidua and chorionic villi of early pregnancy, and mifepristone treatment significantly increases the number of apoptotic cells. The increased apoptotic events were concomitant with the increased expression of Bax and decreased expression of Bcl-2.
CONCLUSION
This study provides evidence that mifepristone induces histological and subcellular changes in decidua and chorionic villi. Mifepristone modulates the relative ratio of Bax/Bcl-2 and the increased apoptosis contributes to the pregnancy termination at early stage of pregnancy.
Topics: Chorionic Villi; Decidua; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Proto-Oncogene Proteins c-bcl-2; bcl-2-Associated X Protein
PubMed: 35869506
DOI: 10.1186/s40360-022-00592-4 -
Placenta Jun 2022During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade... (Review)
Review
During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.
Topics: Arteries; Decidua; Endothelial Cells; Female; Humans; Pregnancy; Pregnancy Trimester, First; Trophoblasts
PubMed: 35552157
DOI: 10.1016/j.placenta.2022.03.013 -
Cellular and Molecular Life Sciences :... Jun 2020Decidualization is a critical event for the blastocyst implantation, placental development and fetal growth and the normal term. In mice, the embryo implantation to the... (Review)
Review
Decidualization is a critical event for the blastocyst implantation, placental development and fetal growth and the normal term. In mice, the embryo implantation to the uterine epithelial would trigger the endometrial stromal cells to differentiate into decidual stromal cells. However, decidualization in women takes place from the secretory phase of each menstrual cycle and continues to early pregnancy if there is conceptus. Deficient decidualization is often associated with pregnancy specific complications and reproductive disorders. Dramatic changes occur in the gene expression profiles during decidualization, which is coordinately regulated by steroid hormones, growth factors, and molecular and epigenetic mechanisms. Recently, emerging evidences showed that epigenetic modifications, mainly including DNA methylation, histone modification, and non-coding RNAs, play an important role in the decidualization process via affecting the target genes' expression. In this review, we will focus on the epigenetic modifications in decidualization and open novel avenues to predict and treat the pregnancy complications caused by abnormal decidualization.
Topics: Animals; DNA Methylation; Decidua; Endometrium; Epigenesis, Genetic; Female; Histone Code; Humans; Pregnancy; Stromal Cells
PubMed: 31813015
DOI: 10.1007/s00018-019-03395-9 -
Placenta Mar 2015Pre-eclampsia (PE) is characterized by failed remodeling of maternal vessels perfusing the placenta. Blood vessels and lymphatic system are involved in vessel remodeling...
INTRODUCTION
Pre-eclampsia (PE) is characterized by failed remodeling of maternal vessels perfusing the placenta. Blood vessels and lymphatic system are involved in vessel remodeling and flow homeostasis in the uterus during pregnancy. This study aims to investigate the involvement of angiogenesis and lymphangiogenesis in PE.
METHODS
Placental and decidual tissues were obtained from pregnancies with PE (n = 90), including PE cases with decidual vasculopathy (DV) (n = 52) and without DV (n = 38), and healthy pregnancies (control, n = 20). The clinical characteristics of these groups were analyzed. The expression levels of VEGF1, CD34, PROX-1, VEGFR3, and CD31 in the placenta and decidua were detected through immunohistochemistry, reverse-transcription polymerase chain reaction, and Western blot.
RESULTS
The lymphangiogenic markers PROX-1 and VEGFR3 were negatively expressed in the placenta but positively expressed in the decidua. The expression levels of the angiogenic markers VEGF1 and CD34 and the panendothelial marker CD31 were significantly lower in the placenta and decidua of the PE group than in those of the control group. The expression levels of VEGF1, CD34, and CD31 were significantly lower in the placenta and decidua with DV than in those without DV. Furthermore, the expression trends of PROX-1 and VEGFR3 was similar to those of VEGF1, CD34, and CD31 among the groups.
CONCLUSIONS
Lymphangiogenesis occurred in the decidua but not in the placenta. Impaired angiogenesis and lymphangiogenesis were associated with PE, particularly in the presence of DV.
Topics: Adult; Antigens, CD34; Biomarkers; Decidua; Down-Regulation; Female; Gene Expression Regulation, Developmental; Homeodomain Proteins; Humans; Lymphangiogenesis; Lymphangitis; Peripheral Vascular Diseases; Placenta; Platelet Endothelial Cell Adhesion Molecule-1; Pre-Eclampsia; Pregnancy; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-3; Vascular Remodeling; Vasculitis
PubMed: 25586742
DOI: 10.1016/j.placenta.2014.12.013 -
Human Reproduction (Oxford, England) Oct 2019What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and placenta? (Observational Study)
Observational Study
STUDY QUESTION
What is the stiffness (elastic modulus) of human nonpregnant secretory phase endometrium, first trimester decidua, and placenta?
SUMMARY ANSWER
The stiffness of decidua basalis, the site of placental invasion, was an order of magnitude higher at 103 Pa compared to 102 Pa for decidua parietalis, nonpregnant endometrium and placenta.
WHAT IS KNOWN ALREADY
Mechanical forces have profound effects on cell behavior, regulating both cell differentiation and migration. Despite their importance, very little is known about their effects on blastocyst implantation and trophoblast migration during placental development because of the lack of mechanical characterization at the human maternal-fetal interface.
STUDY DESIGN, SIZE, DURATION
An observational study was conducted to measure the stiffness of ex vivo samples of human nonpregnant secretory endometrium (N = 5) and first trimester decidua basalis (N = 6), decidua parietalis (N = 5), and placenta (N = 5). The stiffness of the artificial extracellular matrix (ECM), Matrigel®, commonly used to study migration of extravillous trophoblast (EVT) in three dimensions and to culture endometrial and placental organoids, was also determined (N = 5).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Atomic force microscopy was used to perform ex vivo direct measurements to determine the stiffness of fresh tissue samples. Decidua was stained by immunohistochemistry (IHC) for HLA-G+ EVT to confirm whether samples were decidua basalis or decidua parietalis. Endometrium was stained with hematoxylin and eosin to confirm the presence of luminal epithelium. Single-cell RNA sequencing data were analyzed to determine expression of ECM transcripts by decidual and placental cells. Fibrillin 1, a protein identified by these data, was stained by IHC in decidua basalis.
MAIN RESULTS AND THE ROLE OF CHANCE
We observed that decidua basalis was significantly stiffer than decidua parietalis, at 1250 and 171 Pa, respectively (P < 0.05). The stiffness of decidua parietalis was similar to nonpregnant endometrium and placental tissue (250 and 232 Pa, respectively). These findings suggest that it is the presence of invading EVT that is driving the increase in stiffness in decidua basalis. The stiffness of Matrigel® was found to be 331 Pa, significantly lower than decidua basalis (P < 0.05).
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
Tissue stiffness was derived by ex vivo measurements on blocks of fresh tissue in the absence of blood flow. The nonpregnant endometrium samples were obtained from women undergoing treatment for infertility. These may not reflect the stiffness of endometrium from normal fertile women.
WIDER IMPLICATIONS OF THE FINDINGS
These results provide direct measurements of tissue stiffness during the window of implantation and first trimester of human pregnancy. They serve as a basis of future studies exploring the impact of mechanics on embryo implantation and development of the placenta. The findings provide important baseline data to inform matrix stiffness requirements when developing in vitro models of trophoblast stem cell development and migration that more closely resemble the decidua in vivo.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported by the Centre for Trophoblast Research, the Wellcome Trust (090108/Z/09/Z, 085992/Z/08/Z), the Medical Research Council (MR/P001092/1), the European Research Council (772426), an Engineering and Physical Sciences Research Council Doctoral Training Award (1354760), a UK Medical Research Council and Sackler Foundation Doctoral Training Grant (RG70550) and a Wellcome Trust Doctoral Studentship (215226/Z/19/Z).
Topics: Blastocyst; Cell Movement; Collagen; Decidua; Drug Combinations; Elastic Modulus; Elasticity Imaging Techniques; Embryo Implantation; Endometrium; Extracellular Matrix; Female; Humans; Laminin; Microscopy, Atomic Force; Placenta; Placentation; Pregnancy; Pregnancy Trimester, First; Proteoglycans
PubMed: 31579915
DOI: 10.1093/humrep/dez139 -
Reproductive Biology and Endocrinology... Feb 2022In early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP)...
BACKGROUND
In early pregnancy, differentiating between a normal intrauterine pregnancy (IUP) and abnormal gestations including early pregnancy loss (EPL) or ectopic pregnancy (EP) is a major clinical challenge when ultrasound is not yet diagnostic. Clinical treatments for these outcomes are drastically different making early, accurate diagnosis imperative. Hence, a greater understanding of the biological mechanisms involved in these early pregnancy complications could lead to new molecular diagnostics.
METHODS
Trophoblast and endometrial tissue was collected from consenting women having an IUP (n = 4), EPL (n = 4), or EP (n = 2). Samples were analyzed by LC-MS/MS followed by a label-free proteomics analysis in an exploratory study. For each tissue type, pairwise comparisons of different pregnancy outcomes (EPL vs. IUP and EP vs. IUP) were performed, and protein changes having a fold change ≥ 3 and a Student's t-test p-value ≤ 0.05 were defined as significant. Pathway and network classification tools were used to group significantly changing proteins based on their functional similarities.
RESULTS
A total of 4792 and 4757 proteins were identified in decidua and trophoblast proteomes. For decidua, 125 protein levels (2.6% of the proteome) were significantly different between EP and IUP, whereas EPL and IUP decidua were more similar with only 68 (1.4%) differences. For trophoblasts, there were 66 (1.4%) differences between EPL and IUP. However, the largest group of 344 differences (7.2%) was observed between EP and IUP trophoblasts. In both tissues, proteins associated with ECM remodeling, cell adhesion and metabolic pathways showed decreases in EP specimens compared with IUP and EPL. In trophoblasts, EP showed elevation of inflammatory and immune response pathways.
CONCLUSIONS
Overall, differences between an EP and IUP are greater than the changes observed when comparing ongoing IUP and nonviable intrauterine pregnancies (EPL) in both decidua and trophoblast proteomes. Furthermore, differences between EP and IUP were much higher in the trophoblast than in the decidua. This observation is true for the total number of protein changes as well as the extent of changes in upstream regulators and related pathways. This suggests that biomarkers and mechanisms of trophoblast function may be the best predictors of early pregnancy location and viability.
Topics: Abortion, Spontaneous; Adult; Case-Control Studies; Decidua; Embryo Implantation; Female; Fetal Viability; Gestational Age; Humans; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy, Ectopic; Proteome; Signal Transduction; Trophoblasts; Uterus; Young Adult
PubMed: 35189928
DOI: 10.1186/s12958-022-00908-3 -
Advances in Anatomy, Embryology, and... 2015Implantation and the establishment of pregnancy are critical for the propagation of the species, but yet remain the limiting steps in human and primate reproduction.... (Review)
Review
Implantation and the establishment of pregnancy are critical for the propagation of the species, but yet remain the limiting steps in human and primate reproduction. Successful implantation requires a competent blastocyst and a receptive endometrium during a specific window of time during the menstrual cycle to initiate the bilateral communication required for the establishment of a successful pregnancy. This chapter provides an overview of these processes and discusses the molecular mechanisms associated with implantation of the blastocyst and decidualization of the uterus in primates.
Topics: Animals; Decidua; Embryo Implantation; Endometrium; Female; Humans; Pregnancy; Primates
PubMed: 26450500
DOI: 10.1007/978-3-319-15856-3_10 -
Proceedings of the National Academy of... Aug 2022The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent...
The pregnant uterus is an immunologically rich organ, with dynamic changes in the inflammatory milieu and immune cell function underlying key stages of pregnancy. Recent studies have implicated dysregulated expression of the interleukin-1 (IL-1) family cytokine, IL-33, and its receptor, ST2, in poor pregnancy outcomes in women, including recurrent pregnancy loss, preeclampsia, and preterm labor. How IL-33 supports pregnancy progression in vivo is not well understood. Here, we demonstrate that maternal IL-33 signaling critically regulates uterine tissue remodeling and immune cell function during early pregnancy in mice. IL-33-deficient dams exhibit defects in implantation chamber formation and decidualization, and abnormal vascular remodeling during early pregnancy. These defects coincide with delays in early embryogenesis, increased resorptions, and impaired fetal and placental growth by late pregnancy. At a cellular level, myometrial fibroblasts, and decidual endothelial and stromal cells, are the main IL-33 cell types in the uterus during decidualization and early placentation, whereas ST2 is expressed by uterine immune populations associated with type 2 immune responses, including ILC2s, Tregs, CD4 T cells, M2- and cDC2-like myeloid cells, and mast cells. Early pregnancy defects in IL-33-deficient dams are associated with impaired type 2 cytokine responses by uterine lymphocytes and fewer Arginase-1 macrophages in the uterine microenvironment. Collectively, our data highlight a regulatory network, involving crosstalk between IL-33-producing nonimmune cells and ST2 immune cells at the maternal-fetal interface, that critically supports pregnancy progression in mice. This work has the potential to advance our understanding of how IL-33 signaling may support optimal pregnancy outcomes in women.
Topics: Animals; Decidua; Female; Fetus; Interleukin-1 Receptor-Like 1 Protein; Interleukin-33; Lymphocytes; Mice; Placenta; Placentation; Pregnancy; Uterus
PubMed: 35994660
DOI: 10.1073/pnas.2123267119 -
American Journal of Reproductive... Jun 2021Uteroplacental acute atherosis is a type of arterial vascular disease that affects the placenta during pregnancy and predominates in the maternal spiral arteries in the... (Review)
Review
Uteroplacental acute atherosis is a type of arterial vascular disease that affects the placenta during pregnancy and predominates in the maternal spiral arteries in the decidua basalis layer of the pregnant uterus. This condition is characterized by fibrin-like necrosis of the blood vessel walls, the accumulation of macrophages containing fat (foam cells), and the infiltration of macrophages around blood vessels. Uteroplacental acute atherosis is rare in normal pregnancy but occurs more frequently in patients with pregnancy complications, including preeclampsia, spontaneous preterm labor, preterm prelabor rupture of membranes, mid-trimester spontaneous abortion, fetal death, and small-for-gestational age. It is believed that the mechanisms underlying the development of uteroplacental acute atherosis are related to the incomplete physiological transformation of spiral arteries, placental inflammation, abnormal lipid metabolism, and oxidative stress. In this review, we describe the pathogenesis of uteroplacental acute atherosis to provide reference guidelines for the future prevention and treatment of uteroplacental acute atherosclerotic disease.
Topics: Atherosclerosis; Decidua; Female; Humans; Placenta; Pregnancy; Uterine Artery
PubMed: 33533529
DOI: 10.1111/aji.13397 -
Journal of Assisted Reproduction and... May 2016
Review
Topics: Abortion, Habitual; Adult; Blastocyst; Chromosome Aberrations; Decidua; Embryo Implantation; Female; Fertility; Humans; Karyotype
PubMed: 26843392
DOI: 10.1007/s10815-016-0658-8