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The Journal of Obstetrics and... Jul 2020Fine-tuning of the endometrium during the evanescent 'window of implantation' relies upon an array of diverse and redundant signaling molecules, particularly the ovarian... (Review)
Review
Fine-tuning of the endometrium during the evanescent 'window of implantation' relies upon an array of diverse and redundant signaling molecules, particularly the ovarian steroids E2 and P4, but also growth factors, eicosanoids, and vitamins including the vitamin A compounds (retinoids). Pregnancy complications such as preeclampsia (PE) can result from aberrations in the production or function of these molecules that arise during this critical period of decidual development. Such aberrations may be reflected by incomplete decidualization, reduced spiral artery modification, and/or loss of immune tolerance to the developing fetus. Our understanding of the role of the active retinoid metabolite all-trans retinoic acid (RA) in maintaining immune balance in certain tissues, along with data describing its role in decidualization, present a compelling argument that aberrant RA signaling in the decidua can play a significant role in the etiology of PE. Recent findings that decidualization and expression of the anti-angiogenic gene product, 'soluble fms-like tyrosine kinase-1' (sFLT1) are negatively correlated and that sFLT1 expression is directly inhibited by RA, provide additional evidence of the critical role of this retinoid in regulating early vascular development in the decidua. This review provides insight into the production and function of RA in the decidua and how modifications in its metabolism and signaling might lead to certain pregnancy disorders such as PE.
Topics: Decidua; Female; Humans; Pre-Eclampsia; Pregnancy; Tretinoin; Vascular Endothelial Growth Factor Receptor-1
PubMed: 32343034
DOI: 10.1111/jog.14262 -
Biomolecules Jan 2022A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual... (Review)
Review
A high number of leucocytes reside in the human endometrium and are distributed differentially during the menstrual cycle and pregnancy. During early pregnancy, decidual natural killer (dNK) cells are the most common type of natural killer (NK) cells in the uterus. The increase in the number of uterine NK (uNK) cells during the mid-secretory phase of the menstrual cycle, followed by further increase of dNK cells in early pregnancy, has heightened interest in their involvement during pregnancy. Extensive research has revealed various roles of dNK cells during pregnancy including the formation of new blood vessels, migration of trophoblasts, and immunological tolerance. The present review article is focused on the significance of NK cells during pregnancy and their role in pregnancy-related diseases. The article will provide an in-depth review of cellular and molecular interactions during pregnancy and related disorders, with NK cells playing a pivotal role. Moreover, this study will help researchers to understand the physiology of normal pregnancy and related complications with respect to NK cells, so that future research work can be designed to alleviate the complications.
Topics: Decidua; Female; Humans; Immune Tolerance; Killer Cells, Natural; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 35053216
DOI: 10.3390/biom12010068 -
Mitochondrial DNA. Part B, Resources Feb 2021L. and Forsk. belong to the Capparaceae family. The two species are important medicinal plants uses in treatment of various ailments. In this study, we present the...
L. and Forsk. belong to the Capparaceae family. The two species are important medicinal plants uses in treatment of various ailments. In this study, we present the complete chloroplast genomes of the two species. The complete plastome genomes of the two species have a circular structure and a length of 157,728 bp in and 157,573 bp in and GC content of 35.91, 35.96% respectively. The chloroplast genome of and is divided into four regions: LSC of 86,732 and 85,950 bp respectively, SSC from 18,322 to 18,621 bp and a pair of inverted repeats 26,337 and 26,501 bp each. Both of the chloroplast genomes contained 115 different genes, including 80 protein coding genes, 31 tRNA genes and four rRNA genes. A phylogenetic analysis demonstrated that . is sister to . The two species are sister to .
PubMed: 33681464
DOI: 10.1080/23802359.2020.1852902 -
Scientific Reports Mar 2022Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors...
Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors important for its function remain unclear. Renalase is a pro-survival, anti-inflammatory flavoprotein found to be critical in other tissues. We examined the potential role of renalase in placental development. PCR, bulk RNA sequencing, immunohistochemistry, and immunofluorescence for renalase and its binding partners, PMCA4b and PZP, were performed on human placental tissue from second-trimester and full-term placentas separated into decidua, placental villi and chorionic plates. Quantification of immunohistochemistry was used to localize renalase across time course from 17 weeks to term. Endogenous production of renalase was examined in placental tissue and organoids. Renalase and its receptor PMCA4b transcripts and proteins were present in all layers of the placenta. Estimated RNLS protein levels did not change with gestation in the decidual samples. However, placental villi contained more renalase immunoreactive cells in fetal than full-term placental samples. RNLS co-labeled with markers for Hofbauer cells and trophoblasts within the placental villi. Endogenous production of RNLS, PMCA4b, and PZP by trophoblasts was validated in placental organoids. Renalase is endogenously expressed throughout placental tissue and specifically within Hofbauer cells and trophoblasts, suggesting a potential role for renalase in placental development and function. Future studies should assess renalase's role in normal and diseased human placenta.
Topics: Chorionic Villi; Decidua; Female; Humans; Monoamine Oxidase; Placenta; Placentation; Plasma Membrane Calcium-Transporting ATPases; Pregnancy; Trophoblasts
PubMed: 35322081
DOI: 10.1038/s41598-022-08817-6 -
Biomolecules May 2021Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising... (Review)
Review
Preeclampsia (PE) is a serious disease that can be fatal for the mother and fetus. The two-stage theory has been proposed as its cause, with the first stage comprising poor placentation associated with the failure of fertilized egg implantation. Successful implantation and placentation require maternal immunotolerance of the fertilized egg as a semi-allograft and appropriate extravillous trophoblast (EVT) invasion of the decidua and myometrium. The disturbance of EVT invasion during implantation in PE results in impaired spiral artery remodeling. PE is thought to be caused by hypoxia during remodeling failure-derived poor placentation, which results in chronic inflammation. High-mobility group protein A (HMGA) is involved in the growth and invasion of cancer cells and likely in the growth and invasion of trophoblasts. Its mechanism of action is associated with immunotolerance. Thus, HMGA is thought to play a pivotal role in successful pregnancy, and its dysfunction may be related to the pathogenesis of PE. The evaluation of HMGA function and its changes in PE might confirm that it is a reliable biomarker of PE and provide prospects for PE treatment through the induction of EVT proliferation and invasion during the implantation.
Topics: Animals; Cell Proliferation; Decidua; Female; HMGA1a Protein; Humans; Pre-Eclampsia; Pregnancy; Trophoblasts
PubMed: 34072941
DOI: 10.3390/biom11060822 -
Endocrine Journal May 2023Decidualization is a process of differentiation of human endometrial stromal cells (hESCs) accompanied by dramatic changes in cellular functions. This process is... (Review)
Review
Decidualization is a process of differentiation of human endometrial stromal cells (hESCs) accompanied by dramatic changes in cellular functions. This process is critical for embryo implantation and the establishment of pregnancy. Impairment of decidualization of hESCs leads to implantation failure, miscarriage, and unexplained infertility. The present review focuses on the metabolic changes in hESCs during decidualization. One of the changes taking place is in the glucose metabolism. Glucose uptake increases during decidualization because glucose is essential for the decidualization of hESCs. In hESCs, GLUT1 is highly expressed and involved in the increase of glucose uptake during decidualization. The up-regulation of GLUT1 is mediated by an epigenetic mechanism, which is regulated by CCAAT enhancer-binding protein β (C/EBPβ) and Wilms tumor 1 (WT1). Another metabolic change is in the lipid metabolism. Lipid accumulation in hESCs increases during decidualization. This increase is mediated by very low-density lipoprotein receptor (VLDLR). The up-regulation of VLDLR is regulated by WT1. In contrast to glucose, lipid is not essential for decidualization of hESCs. Endometrial cells have been implicated as important sources of nutrition for the embryo. hESCs may increase glucose and lipid storage so that they can supply them to the embryo during the implantation process. Taken together, decidualization is the process accompanied by metabolic changes, which may be associated with successful implantation.
Topics: Pregnancy; Female; Humans; Decidua; Glucose Transporter Type 1; Lipid Metabolism; Glucose; Endometrium; Stromal Cells; Lipids
PubMed: 37081638
DOI: 10.1507/endocrj.EJ23-0099 -
Pathogens (Basel, Switzerland) Dec 2023Infection by species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring.... (Review)
Review
Infection by species in pregnant animals and humans is associated with an increased risk of abortion, preterm birth, and transmission of the infection to the offspring. The pathogen has a marked tropism for the placenta and the pregnant uterus and has the ability to invade and replicate within cells of the maternal-fetal unit, including trophoblasts and decidual cells. Placentitis is a common finding in infected pregnant animals. Several proinflammatory factors have been found to be increased in both the placenta of -infected animals and in trophoblasts or decidual cells infected in vitro. As normal pregnancies require an anti-inflammatory placental environment during most of the gestational period, -induced placentitis is thought to be associated with the obstetric complications of brucellosis. A few studies suggest that the blockade of proinflammatory factors may prevent abortion in these cases.
PubMed: 38133333
DOI: 10.3390/pathogens12121450 -
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 -
Journal of Immunology (Baltimore, Md. :... Jul 2023Immunological tolerance toward the semiallogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the...
Immunological tolerance toward the semiallogeneic fetus is one of many maternal adaptations required for a successful pregnancy. T cells are major players of the adaptive immune system and balance tolerance and protection at the maternal-fetal interface; however, their repertoire and subset programming are still poorly understood. Using emerging single-cell RNA sequencing technologies, we simultaneously obtained transcript, limited protein, and receptor repertoire at the single-cell level, from decidual and matched maternal peripheral human T cells. The decidua maintains a tissue-specific distribution of T cell subsets compared with the periphery. We find that decidual T cells maintain a unique transcriptome programming, characterized by restraint of inflammatory pathways by overexpression of negative regulators (DUSP, TNFAIP3, ZFP36) and expression of PD-1, CTLA-4, TIGIT, and LAG3 in some CD8 clusters. Finally, analyzing TCR clonotypes demonstrated decreased diversity in specific decidual T cell populations. Overall, our data demonstrate the power of multiomics analysis in revealing regulation of fetal-maternal immune coexistence.
Topics: Pregnancy; Female; Humans; Decidua; Proteogenomics; T-Lymphocyte Subsets; Transcriptome; Fetus
PubMed: 37195197
DOI: 10.4049/jimmunol.2200061 -
Reproductive Sciences (Thousand Oaks,... Nov 2023Recurrent spontaneous abortion (RSA) is one of the most common complications during pregnancy and seriously affects women's physical and mental health. About 50% of RSA...
Recurrent spontaneous abortion (RSA) is one of the most common complications during pregnancy and seriously affects women's physical and mental health. About 50% of RSA cases are of unknown etiology. Our previous study found that the decidual tissue of patients with unexplained recurrent spontaneous abortion (URSA) had low expression levels of serum and glucocorticoid-induced protein kinase (SGK) 1. Endometrial decidualization is a key link in the early stage of pregnancy and is crucial to the development and maintenance of pregnancy. Decidualization is the proliferation and differentiation of endometrial stromal cells into deciduals, which involves a complex physiological process such as ovarian steroid hormones (estrogen, progesterone, prolactin, etc.), growth factors, and intercellular signaling. The binding of estrogen and its receptor stimulates the synthesis of endometrial deciduating markers prolactin (PRL) and insulin-like growth factor binding protein 1 (IGFBP-1), which mediates the occurrence of decidualization. Among them, SGK1/ENaC is a signaling pathway closely related to decidualization. The purpose of this study was to further investigate the expression of SGK1 and decidualization-related molecules in the decidual tissue of URSA patients and to explore the potential mechanism of SGK1's protective effect in URSA patients and in mouse models. Decidual tissue samples from 30 URSA patients and 30 women who actively terminated pregnancy were collected, and a URSA mouse model was established and treated with dydrogesterone. Expression levels of SGK1 and its signaling pathway-related proteins (p-Nedd4-2, 14-3-3 protein and ENaC-a), estrogen and progesterone receptors (ERβ, PR), and decidualization markers (PRLR, IGFBP-1) were assessed. Our study found that SGK1, p-Nedd4-2, 14-3-3 proteins, and ENaC-a expression levels were reduced in the decidual tissue, the SGK1/ENaC signaling pathway was inhibited, and the expression levels of the decidualization markers PRLR and IGFBP-1 were downregulated in the URSA group compared with the controls. Additionally, the concentrations of E, P, and PRL in the serum of mice were decreased in the URSA group compared with the controls. However, SGK1/ENaC pathway-related proteins, estrogen and progesterone and their receptors, and decidualization-related molecules were upregulated by dydrogesterone. These data suggest that estrogen and progesterone can induce decidualization by activating the SGK1/ENaC signaling pathway; disruption of this pathway can lead to the development of URSA. Dydrogesterone can increase the expression level of SGK1 protein in decidual tissue.
Topics: Humans; Pregnancy; Female; Mice; Animals; Progesterone; Decidua; Insulin-Like Growth Factor Binding Protein 1; Abortion, Spontaneous; Prolactin; Dydrogesterone; Signal Transduction; Estrogens; Abortion, Habitual; Stromal Cells
PubMed: 37280474
DOI: 10.1007/s43032-023-01273-1