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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 -
Frontiers in Immunology 2022The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This...
The maternal-fetal immune disorder is considered to be an important factor of preterm birth (PTB); however, the underlying mechanism is still not fully understood. This study was designed to explore the innate and adaptive immune features in the decidua during term and preterm labor. Women delivered at term or preterm were classified into four groups: term not in labor (TNL, N=19), term in labor (TL, N=17), preterm not in labor (PNL, N=10), and preterm in labor (PIL, N=10). Decidua basalis and parietalis were collected and analyzed for macrophage subtypes (M1 and M2) as well as T helper 1 (Th1), Th2, Th17 and regulatory T (Treg) cells by flow cytometry and immunohistochemistry. Our results demonstrated significantly decreased frequencies of M2 cells and elevated M1/M2 ratio in the PIL group compared to that in the PNL group in both decidua basalis and parietalis, whereas no significant differences were found between the above two groups in both sites in terms of the polarization status of Th cells. On the contrary, macrophage subsets were comparable in the TL and TNL groups, whereas elevated Th1 percentages and Th1/Th2 ratio were observed in TL women compared to that in TNL women in the decidua. Interestingly, although the frequencies and ratios of Th17 and Treg were comparable among the four groups, the Th17/Treg ratios of these groups were significantly increased in decidua basalis than that in decidua parietalis. Collectively, the M1/M2 imbalance is associated with the breakdown of maternal-fetal immune tolerance during PTB, whereas the aberrant Th1/Th2 profile plays an important role in immune disorder during term labor. Moreover, Th17/Treg deviation is more remarkable in decidua basalis than in decidua parietalis.
Topics: Decidua; Female; Flow Cytometry; Humans; Infant, Newborn; Labor, Obstetric; Obstetric Labor, Premature; Pregnancy; Premature Birth
PubMed: 35757768
DOI: 10.3389/fimmu.2022.877314 -
Nature Reviews. Immunology Apr 2023The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the... (Review)
Review
The role of the maternal immune system in reproductive success in humans remains controversial. Here we focus on the events that occur in the maternal decidua during the first few weeks of human pregnancy, because this is the site at which maternal leukocytes initially interact with and can recognize fetal trophoblast cells, potentially involving allorecognition by both T cells and natural killer (NK) cells. NK cells are the dominant leukocyte population in first-trimester decidua, and genetic studies point to a role of allorecognition by uterine NK cells in establishing a boundary between the mother and the fetus. By contrast, definitive evidence that allorecognition by decidual T cells occurs during the first trimester is lacking. Thus, our view is that during the crucial period when the placenta is established, damaging T cell-mediated adaptive immune responses towards placental trophoblast are minimized, whereas NK cell allorecognition contributes to successful implantation and healthy pregnancy.
Topics: Pregnancy; Humans; Female; Trophoblasts; Placenta; Decidua; Pregnancy Trimester, First; Killer Cells, Natural
PubMed: 36192648
DOI: 10.1038/s41577-022-00777-2 -
Communications Biology May 2023Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival,...
Decidualization of human endometrial stromal cells (hESCs) is essential for the maintenance of pregnancy, which depends on the fine-tuned regulation of hESCs survival, and its perturbation contributes to pregnancy loss. However, the underlying mechanisms responsible for functional deficits in decidua from recurrent spontaneous abortion (RSA) patients have not been elucidated. Here, we observed that JAZF1 was significantly downregulated in stromal cells from RSA decidua. JAZF1 depletion in hESCs resulted in defective decidualization and cell death through apoptosis. Further experiments uncovered G0S2 as a important driver of hESCs apoptosis and decidualization, whose transcription was repressed by JAZF1 via interaction with G0S2 activator Purβ. Moreover, the pattern of low JAZF1, high G0S2 and excessive apoptosis in decidua were consistently observed in RSA patients. Collectively, our findings demonstrate that JAZF1 governs hESCs survival and decidualization by repressing G0S2 transcription via restricting the activity of Purβ, and highlight the clinical implications of these mechanisms in the pathology of RSA.
Topics: Pregnancy; Female; Humans; Endometrium; Decidua; Abortion, Habitual; Stromal Cells; DNA-Binding Proteins; Co-Repressor Proteins; Cell Cycle Proteins
PubMed: 37244968
DOI: 10.1038/s42003-023-04931-x -
Placenta Sep 2023Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to... (Review)
Review
Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy.
Topics: Pregnancy; Female; Humans; Trophoblasts; Placenta; Uterus; Arteries; Abortion, Spontaneous; Pre-Eclampsia; Vascular Remodeling; Decidua
PubMed: 37308346
DOI: 10.1016/j.placenta.2023.05.013 -
Human Immunology May 2021The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems... (Review)
Review
The semi-allogeneic fetus develops in a uniquely immune tolerant environment within the uterus. For successful pregnancy, both the innate and adaptive immune systems must favor acceptance of the fetal allograft. Macrophages are the second most abundant immune cells after natural killer (NK) cells in the decidua. In coordination with decidual NK cells and dendritic cells, macrophages aid in implantation, vascular remodeling, placental development, immune tolerance to placental cells, and maintenance of tissue homeostasis at the maternal-fetal interface. Decidual macrophages show the classical activated (M1) and alternatively activated (M2) phenotypes under the influence of the local milieu of growth factors and cytokines, and appropriate temporal regulation of the M1/M2 switch is vital for successful pregnancy. Disturbances in the mechanisms that control the M1/M2 balance and associated functions during pregnancy can trigger a spectrum of pregnancy complications ranging from preeclampsia and fetal growth restriction to preterm delivery. This review addresses various mechanisms of tolerance, focusing on the basic biology of macrophages, their plasticity and polarization, and their protective roles at the immune-privileged maternal-fetal interface, including direct and indirect roles in promoting fetomaternal immune tolerance.
Topics: Animals; Decidua; Female; Histocompatibility, Maternal-Fetal; Humans; Immune Tolerance; Macrophages; Pregnancy; Pregnancy Complications; Th1-Th2 Balance
PubMed: 33715911
DOI: 10.1016/j.humimm.2021.02.013 -
Molecular Human Reproduction Apr 2023Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes...
Uterine glands and, by inference, their secretions impact uterine receptivity, blastocyst implantation, stromal cell decidualization, and placental development. Changes in gland function across the menstrual cycle are primarily governed by the steroid hormones estrogen (E2) and progesterone (P4) but can also be influenced by extrinsic factors from the stroma. Using a human endometrial epithelial organoid system, transcriptome and proteome analyses identified distinct responses of the organoids to steroid hormones and prostaglandin E2 (PGE2). Notably, P4 and PGE2 modulated the basolateral secretion of organoid proteins, particularly cystatin C (CST3), serpin family A member 3 (SERPINA3), and stanniocalcin 1 (STC1). CST3, but not SERPINA3 or STC1, attenuated the in vitro stromal decidualization response to steroid hormones and PGE2. These findings provide evidence that uterine gland-derived factors impact stromal cell decidualization, which has implications for pregnancy establishment and fertility in women.
Topics: Humans; Pregnancy; Female; Dinoprostone; Placenta; Endometrium; Embryo Implantation; Progesterone; Stromal Cells; Decidua
PubMed: 36821428
DOI: 10.1093/molehr/gaad007 -
Frontiers in Immunology 2023The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment... (Review)
Review
The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.
Topics: Pregnancy; Female; Humans; Prolactin; Decidua; Placenta; Extraembryonic Membranes; Amniotic Fluid
PubMed: 37359537
DOI: 10.3389/fimmu.2023.1212736 -
Best Practice & Research. Clinical... Oct 2019During human pregnancy, trophoblast cells, the main cellular component of the placenta, invade deeply into uterine blood vessels and the modified endometrium (decidua).... (Review)
Review
During human pregnancy, trophoblast cells, the main cellular component of the placenta, invade deeply into uterine blood vessels and the modified endometrium (decidua). Hence, the maternal immune system must adapt to it. A successful pregnancy requires the tolerance of genetically different (allogenic) cells while the mother's immune competence is maintained. This tolerance is ensured through multiple overlapping and occasionally redundant innate and adaptive immune mechanisms. The present article aims to provide a broad overview on uterine immune cell components and the phenotypical and functional changes that they experience during pregnancy. Particularly, we seek to highlight very recent findings in functional adaptations to pregnancy in immune cell populations encountered in the decidua. These adaptations not only ensure tolerance to allogenic trophoblast cells but also promote optimal placental and fetal growth, simultaneously endeavoring to maintain immune surveillance to provide defense against infections.
Topics: Adaptive Immunity; Decidua; Female; Humans; Placenta; Pregnancy; Pregnancy Trimester, First; Trophoblasts; Uterus
PubMed: 31285174
DOI: 10.1016/j.bpobgyn.2019.05.009 -
Journal of Reproductive Immunology Dec 2022Macrophages are professional phagocytes with a wide distribution in all tissues throughout the body. Macrophages play a crucial role in homeostasis and numerous... (Review)
Review
Macrophages are professional phagocytes with a wide distribution in all tissues throughout the body. Macrophages play a crucial role in homeostasis and numerous physiological processes beyond innate and adaptive immunity, including cellular debris removal, metabolic regulation, tissue repair, and tissue remodeling. Uterine macrophages are a heterogeneous and highly plastic subset of immune cells regulated by the local microenvironment and, in addition to their anti-inflammatory and anti-infective functions, support the establishment and maintenance of pregnancy. Comprehensive reviews have summarized the role of decidual macrophages during pregnancy. However, the distribution of macrophages in the endometrium prior to pregnancy, their functional remodeling, and the knock-on effects on subsequent pregnancies have not been elucidated. In this review, we focus on 1) how the phenotypes of endometrial macrophages and their interactions with other endometrial cells indicate or contribute to the subsequent pregnancy, 2) the adaptive switching of endometrial macrophages during the initial establishment of pregnancy, 3) and the pregnancy complications and pregnancy-related disorders associated with endometrial macrophages.
Topics: Pregnancy; Humans; Female; Decidua; Endometrium; Macrophages; Pregnancy Complications
PubMed: 36113384
DOI: 10.1016/j.jri.2022.103736