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Molecular Reproduction and Development Aug 2020Decidualization is a crucial precedent to embryo implantation, as its impairment is a major contributor to female infertility and pregnancy complications. Unraveling the... (Review)
Review
Decidualization is a crucial precedent to embryo implantation, as its impairment is a major contributor to female infertility and pregnancy complications. Unraveling the molecular mechanisms involved in the impairment of decidualization has been a subject of interest in the field of reproductive medicine. Evidence from several experimental settings show that exposure to bisphenol A (BPA), an endocrine-disrupting chemical, affects the expression of several molecules that are involved in decidualization. Both low and high doses of BPA impair decidualization through the dysregulation of estrogen (ER) and progesterone (PR) receptors. Exposure to low doses of BPA leads to decreased levels and activities of several antioxidant enzymes, increased activity of endothelial nitric oxide synthase (eNOS), and increased production of nitric oxide (NO) via the upregulation of ER and PR. Consequently, oxidative stress is induced and decidualization becomes impaired. On the other hand, exposure to high doses of BPA downregulates ER and PR and impairs decidualization through two distinct pathways. One is through the upregulation of early growth response-1 (EGR1) via increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2; and the other is through a reduced serum glucocorticoid-induced kinase-1 (SGK1)-mediated downregulation of epithelial sodium channel-α and the induction of oxidative stress. Thus, regardless of the dose, BPA can impair decidualization to trigger infertility and pregnancy complications. This warrants the need to adopt lifestyles that will decrease the tendency of getting exposed to BPA.
Topics: Animals; Benzhydryl Compounds; Decidua; Embryo Implantation; Embryo Implantation, Delayed; Endocrine Disruptors; Female; Humans; Phenols; Placenta Diseases; Pregnancy; Signal Transduction
PubMed: 32691498
DOI: 10.1002/mrd.23400 -
American Journal of Reproductive... Sep 2023The role of decidual natural killer (dNK) cells in maintaining immune tolerance at the maternal-fetal interface during pregnancy is a significant topic in reproductive... (Review)
Review
The role of decidual natural killer (dNK) cells in maintaining immune tolerance at the maternal-fetal interface during pregnancy is a significant topic in reproductive health. Immune tolerance is essential for a successful pregnancy and involves a complex immune response involving various immune cells and molecules. DNK cells comprise the largest population of lymphocyte subsets found in the decidua and play important roles in maintaining immune tolerance. These cells exert multiple functions to maintain homeostasis of the decidual microenvironment, including modulation of trophoblast invasion, promotion of fetal development, regulation of endometrial decidualization and spiral artery remodeling. DNK cells can also be divided into different subsets based on their functions as NK , NK , and NK cells. However, the relationship between dNK cells function and pregnancy outcomes is complex and poorly understood. In this review, we will focus on the physiological role of dNK cells during pregnancy and highlight the potential role in pathological pregnancies and therapeutic approaches.
Topics: Female; Pregnancy; Humans; Homeostasis; Arteries; Fetal Development; Killer Cells, Natural; Decidua
PubMed: 37641369
DOI: 10.1111/aji.13755 -
Journal of Reproductive Immunology Feb 2021A successful pregnancy requires that the maternal immune system recognizes and tolerates the semi-allogeneic fetus without compromising the capability of protecting both... (Review)
Review
A successful pregnancy requires that the maternal immune system recognizes and tolerates the semi-allogeneic fetus without compromising the capability of protecting both mother and fetus from various pathogens. Decidual macrophages present unique phenotypes to play a key role in the establishment of the immunological aspects of maternal-fetal interaction. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia, recurrent spontaneous miscarriage, preterm labor and fetal growth restriction. Here, we reviewed the latest knowledge on the origin, differentiation, unique phenotype and function of macrophages in normal pregnancy and in pregnancy complications. We mainly focused on the significant roles of decidual macrophages in the process of extravillous trophoblast invasion, spiral arterial remodeling, decidual stromal cells cultivation and immune tolerance maintenance in normal pregnancy, and their pathological roles in pregnancy-related complications, offering more integrated information in maternal-fetal immunity.
Topics: Decidua; Female; Histocompatibility, Maternal-Fetal; Humans; Immune Tolerance; Macrophages; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 33360717
DOI: 10.1016/j.jri.2020.103264 -
Annual Review of Immunology Apr 2023The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth... (Review)
Review
The presence of granulated lymphocytes in the human uterine mucosa, known as decidua during pregnancy, or endometrium otherwise, was first noted in the nineteenth century, but it was not until 1990 that these cells were identified as a type of natural killer (NK) cell. From the outset, uterine NK (uNK) cells were found to be less cytotoxic than their circulating counterparts, peripheral NK (pNK) cells. Recently, unbiased approaches have defined three subpopulations of uNK cells, all of which cluster separately from pNK cells. Here, we review the history of research into uNK cells, including their ability to interact with placental extravillous trophoblast cells and their potential role in regulating placental implantation. We go on to review more recent advances that focus on uNK cell development and heterogeneity and their potential to defend against infection and to mediate memory effects. Finally, we consider how a better understanding of these cells could be leveraged in the future to improve outcomes of pregnancy for mothers and babies.
Topics: Humans; Pregnancy; Female; Animals; Placenta; Uterus; Killer Cells, Natural; Mucous Membrane; Decidua
PubMed: 36630598
DOI: 10.1146/annurev-immunol-102119-075119 -
FASEB Journal : Official Publication of... Dec 2023Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in... (Review)
Review
Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal-fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal-fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal-fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.
Topics: Pregnancy; Female; Humans; Decidua; Placenta; Trophoblasts; Abortion, Spontaneous; Glycolysis
PubMed: 37889786
DOI: 10.1096/fj.202301230R -
Biology of Reproduction Jul 2022During pregnancy, maternal decidual tissue interacts with fetal trophoblasts. They constitute the maternal-fetal interface responsible for supplying nutrition to the... (Review)
Review
During pregnancy, maternal decidual tissue interacts with fetal trophoblasts. They constitute the maternal-fetal interface responsible for supplying nutrition to the fetus. Uterine natural killer (uNK) cells are the most abundant immune cells at the maternal-fetal interface during early pregnancy and play critical roles throughout pregnancy. This review provides current knowledge about the functions of uNK cells. uNK cells have been shown to facilitate remodeling of the spiral artery, control the invasion of extravillous trophoblast (EVT) cells, contribute to the induction and maintenance of immune tolerance, protect against pathogen infection, and promote fetal development. Pregnancy-trained memory of uNK cells improves subsequent pregnancy outcomes. In addition, this review describes the distinct functions of three uNK cell subsets: CD27-CD11b-, CD27+, and CD27-CD11b+ uNK cells.
Topics: Decidua; Female; Humans; Killer Cells, Natural; Pregnancy; Trophoblasts; Uterus
PubMed: 35551350
DOI: 10.1093/biolre/ioac094 -
Journal of Obstetrics and Gynaecology :... Nov 2022The difficulty in maintaining the balance between oxides and antioxidants causes a phenomenon named oxidative stress. Oxidative stress often leads to tissue damage and... (Review)
Review
The difficulty in maintaining the balance between oxides and antioxidants causes a phenomenon named oxidative stress. Oxidative stress often leads to tissue damage and participates in the pathogenesis of a series of diseases. Decidua provides the 'soil' for embryo implantation, and the normal decidualization shows the characteristics of strong antioxidation. Once the mechanism of antioxidant stress goes awry, it will lead to a series of pregnancy-related diseases. In recent years, more and more studies have shown that oxidative stress is involved in pregnancy-related diseases caused by abnormal decidualization of the endometrium. In order to have a more comprehensive understanding of the role of oxidative stress in decidual defect diseases, this paper reviews the common decidual defect diseases in conjunction with relevant regulatory molecules, in order to arouse thinking about the importance of oxidative stress, and to provide more theoretical basis for the aetiology of decidual defects.
Topics: Pregnancy; Female; Humans; Decidua; Endometrium; Embryo Implantation; Pregnancy Complications; Oxidative Stress; Stromal Cells
PubMed: 36373471
DOI: 10.1080/01443615.2022.2144171 -
Journal of Reproductive Immunology Jun 2022The immune cells, especially innate immune cells (Natural Killer cells and Macrophages) residing at the maternal-fetal interface are playing critical roles during...
The immune cells, especially innate immune cells (Natural Killer cells and Macrophages) residing at the maternal-fetal interface are playing critical roles during pregnancy. Here we discuss the immunological characteristic at the maternal-fetal interface during normal pregnancy. These key decidual immune cells are reshaped of their uterus-specific homeostatic functions within this uterus microenvironment. Through emphasizing the similarities and differences between decidua immune microenvironments with tumor or transplantation immune microenvironments, distinctive immune cell niche with activated, tolerant, proangiogenic and nurturing characteristic at the maternal interface is exhibited. Deeper understanding of the immunological microenvironment during pregnancy yield important insight not only into the pathogenesis of various human pregnancy complications, but also suggest ways to better manipulate these immune cells in cancer and transplant organs.
Topics: Decidua; Female; Humans; Killer Cells, Natural; Macrophages; Maternal-Fetal Exchange; Pregnancy; Pregnancy Complications; Uterus
PubMed: 35504113
DOI: 10.1016/j.jri.2022.103632 -
Environmental Research Jul 2023Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the...
Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the outer is in direct contact with maternal blood (decidua placenta), and the inner (villi) directly in contact with the fetus. Environmental contaminants, such as per- and polyfluoroalkyl substances (PFAS) also demonstrated the ability to cross the tissue multiple layers, posing at risk the health of the fetus. The aim of the present study was to analyse the PFAS amount in decidua and villi placenta explants and to study differences in their distribution among the two side of this organ. The determination of 23 PFAS was carried out by liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM). Our research included women who delivered at term between 2021 and 2022. Our data indicated that all samples contained at least one PFAS, demonstrating the ubiquitarian presence of these compounds in our population. A high occurrence of PFOS, PFOA and PFHxS, followed by PFHxA, PFBS and PFUnA was found. The fluorotelomer 6:2 FTS was also present in more than 40% of samples and this represent the first data on placenta explants. Mean and median PFAS values for decidual explants were 0.5 ng/g and 0.4 ng/g (SD 0.3), while for villi explants mean and median values were 0.6 ng/g and 0.4 ng/g (SD 0.4). A different pattern of accumulation was observed between villi and decidual explants for PFOS, PFOA and PFUnA (villi > decidua) and PFHxA, PFHxS, PFBS and 6:2 FTS (decidua > villi). Even if the mechanism of this selectively accumuation is not yet understood, molecular degree of ionization and its lipophilicity could at least in part explain this difference. This study expands the limited data describing PFAS levels in the placenta and pose attention on PFAS exposure during pregnancy.
Topics: Pregnancy; Humans; Female; Placenta; Fluorocarbons; Mothers; Decidua; Alkanesulfonic Acids; Environmental Pollutants
PubMed: 37119845
DOI: 10.1016/j.envres.2023.115955 -
Molecular and Cellular Endocrinology Mar 2020Spiral artery remodeling, which is indispensable for successful pregnancy, is accomplished by endovascular trophoblasts that move upstream along the arterial wall,... (Review)
Review
Spiral artery remodeling, which is indispensable for successful pregnancy, is accomplished by endovascular trophoblasts that move upstream along the arterial wall, replace the endothelium, and disrupt the muscular lining. This review outlines the possible factors that could regulate endovascular trophoblast differentiation and invasion. First, high oxygen tension in the spiral artery could initiate endovascular trophoblast invasion. Second, activation of maternal decidual natural killer (dNK) cells could support perivascular invasion of interstitial trophoblasts and consequently could facilitate the endovascular trophoblast invasion. Third, maternal platelets trapped by the endovascular trophoblasts could enhance endovascular trophoblast invasion, which is in part mediated by chemokine CCL5 (C-C motif ligand 5) released from the activated platelets and chemokine receptor CCR1 (C-C chemokine receptor type 1) expressed specifically on the endovascular trophoblasts. The rat, in which trophoblast cells exhibit extensive interstitial and endovascular invasion, could be a suitable model animal for the study of human spiral artery remodeling. Apparently paradoxical results came from the rat study, i.e., exposure to hypoxia or depletion of dNK cells resulted in acceleration of the endovascular trophoblast invasion. This implies the presence of as-yet-undetermined regulator(s) whose effects on endovascular trophoblast invasion surpass the effects of surrounding oxygen tension or maternal dNK cells. In the future, clarification of the molecular differences between human interstitial and endovascular trophoblasts as well as establishment of the pregnant rat model exhibiting shallow endovascular trophoblast invasion and preeclamptic symptoms will contribute to elucidating the mechanism of spiral artery remodeling.
Topics: Animals; Arteries; Decidua; Female; Humans; Placenta; Pregnancy; Rats; Trophoblasts; Uterus; Vascular Remodeling
PubMed: 31899258
DOI: 10.1016/j.mce.2019.110699