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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 -
Placenta Aug 2020Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions.... (Review)
Review
Preeclampsia is the archetype of a spectrum of clinical disorders related to abnormal placental development or function, characterized by placental histological lesions. Among those lesions, decidual vasculopathy is a term used to describe lesions of maternal spiral arteries, which are encountered on placental examination in about half of the women with preeclampsia. The morphological features of the lesions include perivascular lymphocytic infiltration, fibrinoid necrosis and foam cell incorporation within the vessel wall. Due to the resemblance of the latter characteristic to atherosclerosis, they are alternatively termed acute atherosis. Decidual vasculopathy correlates with worse maternal and neonatal outcomes, as well as placental pathology. In this article, we review the available literature on decidual vasculopathy and address the pitfalls in histological analysis of the lesions, including the varying definitions of the lesions and sample collection methods. We also discuss the current evidence on the etiology of the lesions and propose a novel hypothesis linking the three etiological pathways to the formation of decidual vasculopathy and, ultimately, the emergence of the heterogeneous group of placental dysfunction disorders, known as the great obstetric syndromes.
Topics: Arteries; Decidua; Female; Humans; Pre-Eclampsia; Pregnancy; Vascular Diseases; Vascular Remodeling
PubMed: 32792071
DOI: 10.1016/j.placenta.2020.06.020 -
Placenta Dec 2017In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal... (Review)
Review
In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.
Topics: Decidua; Female; Gene Expression; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 28693893
DOI: 10.1016/j.placenta.2017.06.005 -
Oncotarget Oct 2016NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are... (Comparative Study)
Comparative Study
NKp44 and NKp30 splice variant profiles have been shown to promote diverse cellular functions. Moreover, microenvironment factors such as TGF-β, IL-15 and IL-18 are able to influence both NKp44 and NKp30 splice variant profiles, leading to cytokine-associated profiles. Placenta and cancerous tissues have many similarities; both are immunologically privileged sites and both share immune tolerance mechanisms to support tissue development. Therefore, we studied the profiles of NKp44 and NKp30 splice variants in these states by comparing (i) decidua from pregnancy disorder and healthy gestation and (ii) matched normal and cancer tissue. Decidua samples had high incidence of both NKp44 and NKp30. In cancerous state it was different; while NKp30 expression was evident in most cancerous and matched normal tissues, NKp44 incidence was lower and was mostly associated with the cancerous tissues. A NKp44-1dominant inhibitory profile predominated in healthy pregnancy gestation. Interestingly, the NKp44-2/3 activation profile becomes the leading profile in spontaneous abortions, whereas balanced NKp44 profiles were observed in preeclampsia. In contrast, a clear preference for the NKp30a/b profile was evident in the 1st trimester decidua, yet no significant differences were observed for NKp30 profiles between healthy gestation and spontaneous abortions/preeclampsia. Both cancerous and matched normal tissues manifested balanced NKp30c inhibitory and NKp30a/b activation profiles with a NKp44-1dominant profile. However, a shift in NKp30 profiles between matched normal and cancer tissue was observed in half of the cases. To summarize, NKp44 and NKp30 splice variants profiles are tissue/condition specific and demonstrate similarity between placenta and cancerous tissues.
Topics: Abortion, Spontaneous; Decidua; Female; Flow Cytometry; Humans; Immune Privilege; Interleukin-15; Interleukin-18; Killer Cells, Natural; Lymphocytes, Tumor-Infiltrating; Natural Cytotoxicity Triggering Receptor 2; Natural Cytotoxicity Triggering Receptor 3; Neoplasms; Pre-Eclampsia; Pregnancy; RNA Splicing; Transforming Growth Factor beta; Tumor Microenvironment
PubMed: 27765926
DOI: 10.18632/oncotarget.12292 -
Advances in Experimental Medicine and... 2015Embryo implantation requires a reciprocal interaction between the blastocyst and endometrium and is associated with complex regulatory mechanisms. Since their discovery,...
Embryo implantation requires a reciprocal interaction between the blastocyst and endometrium and is associated with complex regulatory mechanisms. Since their discovery, microRNAs became prominent candidates providing missing links for many biological pathways. In recent years, microRNAs were implicated as one of the important players in regulation of various biological and physiological endometrial related processes. This chapter aims to present recent knowledge pertaining to the diverse aspects of microRNAs in the embryo-endometrial relationship. We will focus on the role of microRNAs in decidualization and their part in natural and stimulated cycles. Next, we will present recent studies deliberating the role of microRNAs in recurrent pregnancy loss and in the important phenomenon of recurrent implantation failure. Lastly, demonstrating an important aspect of embryo implantation and invasion, we will outline few microRNA related shared pathways of implantation and carcinogenesis.
Topics: Abortion, Habitual; Animals; Decidua; Embryo Implantation; Embryo Loss; Endometrium; Female; Gene Expression Regulation, Developmental; Humans; MicroRNAs; Pregnancy
PubMed: 26662990
DOI: 10.1007/978-3-319-22380-3_8 -
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 -
Lab on a Chip Nov 2020Maternal infection (i.e., ascending infection) and the resulting host inflammatory response are risk factors associated with spontaneous preterm birth (PTB), a major...
Maternal infection (i.e., ascending infection) and the resulting host inflammatory response are risk factors associated with spontaneous preterm birth (PTB), a major pregnancy complication. However, the path of infection and its propagation from the maternal side to the fetal side have been difficult to study due to the lack of appropriate in vitro models and limitations of animal models. A better understanding of the propagation kinetics of infectious agents and development of the host inflammatory response at the feto-maternal (amniochorion-decidua, respectively) interface (FMi) is critical in curtailing host inflammatory responses that can lead to PTB. To model ascending infection and determine inflammatory responses at the FMi, we developed a microfluidic organ-on-chip (OOC) device containing primary cells from the FMi (decidua, chorion, and amnion [mesenchyme and epithelium]) and collagen matrix harvested from primary tissue. The FMi-OOC is composed of four concentric circular cell/collagen chambers designed to mimic the thickness and cell density of the FMi in vivo. Each layer is connected by arrays of microchannels filled with type IV collagen to recreate the basement membrane of the amniochorion. Cellular characteristics (viability, morphology, production of nascent collagen, cellular transitions, and migration) in the OOC were similar to those seen in utero, validating the physiological relevance and utility of the developed FMi-OOC. The ascending infection model of the FMi-OOC, triggered by exposing the maternal (decidua) side of the OOC to lipopolysaccharide (LPS, 100 ng mL-1), shows that LPS propagated through the chorion, amnion mesenchyme, and reached the fetal amnion within 72 h. LPS induced time-dependent and cell-type-specific pro-inflammatory cytokine production (24 h decidua: IL-6, 48 h chorion: GM-CSF and IL-6, and 72 h amnion mesenchyme and epithelium: GM-CSF and IL-6). Collectively, this OOC model and study successfully modeled ascending infection, its propagation, and distinct inflammatory response at the FMi indicative of pathologic pathways of PTB. This OOC model provides a novel platform to study physiological and pathological cell status at the FMi, and is expected to have broad utility in the field of obstetrics.
Topics: Amnion; Animals; Chorion; Decidua; Female; Lipopolysaccharides; Pregnancy; Premature Birth
PubMed: 33112317
DOI: 10.1039/d0lc00875c -
Science China. Life Sciences Dec 2016During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early... (Review)
Review
During early pregnancy, an orchestrated evolutionary maternal adaption toward tolerance of the semiallogeneic fetus is required to ensure decidualization and early embryo development. Remodeling of the immune system involves natural killer cells (NKs), macrophages, T cells and dendritic cells (DCs) altering the microenvironment in the deciduas. In particular, a unique population of NK cells with a CD56CD16 phenotype in the decidua has been proposed to play a key role in the maternal adaptation to pregnancy. However, there is a tendency for pregnancy immunology to reflect transplantation immunology regarding the assumption that the maternal immune system should be suppressed. This tendency is misleading. We discuss how the immune system is formed in early deciduas and the interactions between maternal NK cells and fetal growth. We propose that the maternal immune response must not be fully suppressed and is even necessary for the local response of uterine NK cells.
Topics: Animals; Cell Communication; Cellular Microenvironment; Decidua; Female; Humans; Killer Cells, Natural; Maternal-Fetal Exchange; Pregnancy; Trophoblasts
PubMed: 27905000
DOI: 10.1007/s11427-016-0337-1 -
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 -
Journal of Reproductive Immunology Feb 2019The purpose of this study was to analyze the involvement of signaling via Interleukin-4-Receptor α (IL4Rα) and Toll like receptor (TLR) 4 at the fetomaternal interface... (Clinical Trial)
Clinical Trial
BACKGROUND
The purpose of this study was to analyze the involvement of signaling via Interleukin-4-Receptor α (IL4Rα) and Toll like receptor (TLR) 4 at the fetomaternal interface in the process of early pregnancy.
PATIENTS AND METHODS
Placenta specimens of 46 patients in early pregnancy were analyzed (normal pregnancy (n = 15), spontaneous (n = 15) and habitual abortion (n = 16)). TLR4 and IL4Rα were analyzed by immunohistochemistry, immunofluorescence and real time PCR. Statistical analysis was carried out using SPSS 23 and Microsoft Excel.
RESULTS
IL4Rα could be detected in trophoblast cells of all groups. It was significantly downregulated in the syncytiotrophoblast of spontaneous and recurrent abortions (p = 0.001), and in decidual tissue of spontaneous abortions (p = 0.001). Expression of TLR4 was decreased in the intermediate villous trophoblast (IVT) and decidua of spontaneous abortions (p = 0.04 & 0.003, respectively). On mRNA level expression of IL4Rα and TLR4 was significantly decreased in the group of recurrent miscarriages (IL4Rα p = 0.002, TLR4 p = 0.004).
CONCLUSION
This study contributes new findings to the understanding of the complex molecular interplay at the fetomaternal interface in normal pregnancy and miscarriages. For the first time signaling via IL4Rα being involved at the very beginning of the generation of new life could demonstrated. Moreover, new evidence was provided regarding TLR4 playing a pivotal role in early pregnancy.
Topics: Abortion, Habitual; Adult; Decidua; Female; Humans; Interleukin-4 Receptor alpha Subunit; Pregnancy; Pregnancy Proteins; Toll-Like Receptor 4
PubMed: 30639993
DOI: 10.1016/j.jri.2018.12.001