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International Journal of Molecular... Feb 2022Preterm birth remains to be one of the most prevalent obstetric complications worldwide. Since there are multiple etiological factors associated with this disease... (Review)
Review
Preterm birth remains to be one of the most prevalent obstetric complications worldwide. Since there are multiple etiological factors associated with this disease process, an integrative literature search in PubMed and Scopus databases on possible mechanism of action and effect of bisphenols on exposure on human or animal placental samples in preterm birth was conducted. From 2332 articles on initial literature search, 63 studies were included for full data extraction. Altogether, several pathways were shown to be possibly affected by bisphenols, leading to dysregulations in structural and endocrine foundation in the placenta, potential induction of senescence and failure of decidualization in the decidua, and possible propagation of inflammation in the fetal membranes. Combined, these actions may eventually counteract bisphenol-induced relaxation of the myometrium and promote contractility alongside fetal membrane weakening. In totality, these individual impairments in gestation-critical processes may lead to failure of maintenance of pregnancy, and thus effecting preterm birth.
Topics: Benzhydryl Compounds; Cellular Senescence; Decidua; Female; Gene Expression Regulation; Humans; Phenols; Pregnancy; Premature Birth; Signal Transduction
PubMed: 35269554
DOI: 10.3390/ijms23052411 -
Journal of Reproductive Immunology Dec 2023A recent meta-analysis revealed that patients with unexplained recurrent pregnancy loss (RPL) show higher insulin resistance compared to healthy controls. However, the...
A recent meta-analysis revealed that patients with unexplained recurrent pregnancy loss (RPL) show higher insulin resistance compared to healthy controls. However, the etiology of RPL remains unknown. Prokineticin (PROK1), a pleiotropic uterine endometrial protein, is important for implantation and decidualization and is regulated by hypoxia and insulin. In this study, we investigated the decidualization status and the role of PROK1 in the decidua of patients with unexplained RPL showing insulin resistance. Thirty-two patients with unexplained RPL were included in this study. Following the diagnosis of a miscarriage, the decidua and villi of the patient were surgically collected. Fasting blood glucose and insulin levels were measured, and HOMA-β was calculated. Using IHC and ELISA, the expression of IGFBP-1, PRL and PROK1 in the decidua and IGF-2 in the villi were analyzed in patients with euploid miscarriage with a high HOMA-β index (n = 8) and compared to controls (euploid miscarriage with normal HOMA-β: n = 12, aneuploid miscarriage with normal HOMA-β: n = 12). The co-localization of PROK1 and IGFBP-1 was observed in the decidua by IHC. In the decidua of RPL patients with high HOMA-β, the expression levels of IGFBP-1 and PRL were significantly lower, whereas the PROK1/IGFBP-1 ratio was significantly higher compared to that of the controls. IGF-2 expression in villi was significantly lower in RPL patients with high HOMA-β. Impaired decidualization and excessive PROK1 production may have pathological implications in patients with unexplained RPL with insulin resistance, especially under the state of hyper insulin production.
Topics: Pregnancy; Female; Humans; Decidua; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor II; Insulin Resistance; Abortion, Habitual; Insulin; Gastrointestinal Hormones; Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
PubMed: 37801889
DOI: 10.1016/j.jri.2023.104155 -
Experimental Cell Research Aug 2022Missed abortion (MA) is a special form of spontaneous abortion that is increasing in incidence. However, the precise molecular mechanisms underlying MA, especially...
Missed abortion (MA) is a special form of spontaneous abortion that is increasing in incidence. However, the precise molecular mechanisms underlying MA, especially regarding the decidua, are poorly understood. Herein, we identified molecular signaling pathways related to MA by comparing the decidua of women experiencing normal pregnancy and MA using a quantitative proteomics approach based on HPLC-MS/MS and iTRAQ labeling. Integrated bioinformatics analysis of villi and decidua was performed to reveal potential crosstalk signals in closely related tissues. We identified 2277 proteins with high confidence in decidua, of which 232 were differentially expressed in MA samples. Specifically, we reported that integrated quantitative proteomic and bioinformatic analysis revealed altered proteins in MA and the mechanisms underpinning MA involved numerous pathways, especially ribosome and cellular metabolism signaling. Moreover, Importin 9, Cullin 1 and COX6C are critical for MA, and their altered expression might contribute to the pathophysiology of MA. In particular, COX6C was dramatically down-regulated in both decidua and villi of MA. COX6C was also found to be highly expressed in syncytiotrophoblastic and cytotrophoblastic cells in villi and widely expressed in decidua of the control group, but dramatically decreased in the MA group. Functional analysis showed that knockdown of COX6C inhibited apoptosis process in both HTR-8 and SiHa cells, suggesting that COX6C may play protective effects in MA. Thus, this study could help to map the regulatory protein network related to MA and contribute to the pathophysiological mechanisms of MA.
Topics: Abortion, Missed; Chorionic Villi; Decidua; Female; Humans; Pregnancy; Proteomics; Tandem Mass Spectrometry
PubMed: 35605648
DOI: 10.1016/j.yexcr.2022.113216 -
International Journal of Biological... 2020The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the... (Review)
Review
The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM. Emerging evidence has shown that collagen and its fragment are expressed at the maternal fetal interface. The regulation of expression of collagen is quite complex, and this process involves a multitude of factors. Collagen exerts a critical role during the successful pregnancy. In addition, the abnormal expressions of collagen and its fragments are associated with certain pathological states associated with pregnancy, including recurrent miscarriage, diabetes mellitus with pregnancy, preeclampsia and so on. In this review, the expression and potential roles of collagen under conditions of physiological and pathological pregnancy are systematically discussed.
Topics: Collagen; Decidua; Female; Gene Expression Regulation; Humans; Maternal-Fetal Exchange; Placenta; Pregnancy
PubMed: 32549767
DOI: 10.7150/ijbs.45586 -
Biology of Reproduction Aug 2022Uterine dysfunctions lead to fertility disorders and pregnancy complications. Normal uterine functions at pregnancy depend on crosstalk among multiple cell types in...
Uterine dysfunctions lead to fertility disorders and pregnancy complications. Normal uterine functions at pregnancy depend on crosstalk among multiple cell types in uterine microenvironments. Here, we performed the spatial transcriptomics and single-cell RNA-seq assays to determine local gene expression profiles at the embryo implantation site of the mouse uterus on pregnancy day 7.5 (D7.5). The spatial transcriptomic annotation identified 11 domains of distinct gene signatures, including a mesometrial myometrium, an anti-mesometrial myometrium, a mesometrial decidua enriched with natural killer cells, a vascular sinus zone for maternal vessel remodeling, a fetal-maternal interface, a primary decidual zone, a transition decidual zone, a secondary decidual zone, undifferentiated stroma, uterine glands, and the embryo. The scRNA-Seq identified 12 types of cells in the D7.5 uterus including three types of stromal fibroblasts with differentiated and undifferentiated markers, one cluster of epithelium including luminal and glandular epithelium, mesothelium, endothelia, pericytes, myelomonocytic cell, natural killer cells, and lymphocyte B. These single-cell RNA signatures were then utilized to deconvolute the cell-type compositions of each individual uterine microenvironment. Functional annotation assays on spatial transcriptomic data revealed uterine microenvironments with distinguished metabolic preferences, immune responses, and various cellular behaviors that are regulated by region-specific endocrine and paracrine signals. Global interactome among regions is also projected based on the spatial transcriptomic data. This study provides high-resolution transcriptome profiles with locality information at the embryo implantation site to facilitate further investigations on molecular mechanisms for normal pregnancy progression.
Topics: Animals; Decidua; Embryo Implantation; Epithelium; Female; Killer Cells, Natural; Mice; Myometrium; Pregnancy; Transcriptome; Uterus
PubMed: 35357464
DOI: 10.1093/biolre/ioac061 -
American Journal of Reproductive... Mar 2016Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte... (Review)
Review
Macrophages perform many specific functions including host defense, homeostasis, angiogenesis, and tissue development. Macrophages are the second most abundant leukocyte population in the non-pregnant endometrium and pregnant decidua and likely play a central role in the establishment and maintenance of normal pregnancy. Importantly, aberrantly activated uterine macrophages can affect trophoblast function and placental development, which may result in various adverse pregnancy outcomes ranging from pre-eclampsia to fetal growth restriction or demise. Only by fully understanding the roles of macrophage in pregnancy will we be able to develop interventions for the treatment of these various pregnancy complications. This review discusses the general origin and classification of monocytes and macrophages and focuses on the phenotype and functional roles of decidual macrophage at the maternal-fetal interface in normal pregnancy, as well as discussing the potential contribution of the abnormal state of these cells to various aspects of pregnancy pathologies.
Topics: Animals; Decidua; Female; Fetal Growth Retardation; Humans; Macrophage Activation; Macrophages; Monocytes; Pregnancy
PubMed: 26750089
DOI: 10.1111/aji.12477 -
Biomolecules Sep 2022Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose... (Review)
Review
Several factors are important for implantation and subsequent placentation in the endometrium, including immunity, angiogenesis, extracellular matrix, glucose metabolism, reactive oxidative stress, and hormones. The involvement or abnormality of these factors can impair canonical decidualization. Unusual decidualization can lead to perinatal complications, such as disruption of trophoblast invasion. Drastic changes in the morphology and function of human endometrial stromal cells (hESCs) are important for decidualization of the human endometrium; hESCs are used to induce optimal morphological and functional decidualization in vitro because they contain estrogen and progesterone receptors. In this review, we will focus on the studies that have been conducted on hESC decidualization, including the results from our laboratory.
Topics: Cells, Cultured; Decidua; Estrogens; Female; Glucose; Humans; Pregnancy; Receptors, Progesterone; Stromal Cells
PubMed: 36139114
DOI: 10.3390/biom12091275 -
International Journal of Molecular... Oct 2019Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy,... (Review)
Review
Recurrent pregnancy loss (RPL) represents an unresolved problem for contemporary gynecology and obstetrics. In fact, it is not only a relevant complication of pregnancy, but is also a significant reproductive disorder affecting around 5% of couples desiring a child. The current knowledge on RPL is largely incomplete, since nearly 50% of RPL cases are still classified as unexplained. Emerging evidence indicates that the endometrium is a key tissue involved in the correct immunologic dialogue between the mother and the conceptus, which is a condition essential for the proper establishment and maintenance of a successful pregnancy. The immunologic events occurring at the maternal-fetal interface within the endometrium in early pregnancy are extremely complex and involve a large array of immune cells and molecules with immunoregulatory properties. A growing body of experimental studies suggests that endometrial immune dysregulation could be responsible for several, if not many, cases of RPL of unknown origin. The present article reviews the major immunologic pathways, cells, and molecular determinants involved in the endometrial dysfunction observed with specific application to RPL.
Topics: Abortion, Habitual; Cytokines; Decidua; Dendritic Cells; Embryo, Mammalian; Endometrium; Female; Humans; Killer Cells, Natural; Macrophages; Pregnancy; T-Lymphocytes, Regulatory
PubMed: 31717776
DOI: 10.3390/ijms20215332 -
Glycobiology May 2017Selectins are a family of calcium-dependent, type I transmembrane, carbohydrate-binding glycoproteins. Selectins and their ligands are not only involved in physiological... (Review)
Review
Selectins are a family of calcium-dependent, type I transmembrane, carbohydrate-binding glycoproteins. Selectins and their ligands are not only involved in physiological processes such as leukocyte homing and pathological processes such as cancer, but also play an essential role in the human implantation. L-selectin and its ligands participate in the adhesion of the blastocyst to the endometrium at the maternal-fetal interface. P-selectin and E-selectin are involved in immune recognition of maternal decidua to the embedded embryo as well as trophoblast migration within decidual spiral arterioles. Moreover, altered expression of selectins and their ligands are found to be associated with some abnormal pregnancies and infertilities. This review focuses on the current progress of research on the role of selectins and their ligands in the human implantation process.
Topics: Decidua; Embryo Implantation; Endometrium; Female; Humans; Ligands; Male; Pregnancy; Selectins; Trophoblasts
PubMed: 28115423
DOI: 10.1093/glycob/cwx009 -
Frontiers in Immunology 2020During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier... (Review)
Review
During pregnancy, the placenta forms the anatomical barrier between the mother and developing fetus. Infectious agents can potentially breach the placental barrier resulting in pathogenic transmission from mother to fetus. Innate immune responses, orchestrated by maternal and fetal cells at the decidual-placental interface, are the first line of defense to avoid vertical transmission. Here, we outline the anatomy of the human placenta and uterine lining, the decidua, and discuss the potential capacity of pathogen pattern recognition and other host defense strategies present in the innate immune cells at the placental-decidual interface. We consider major congenital infections that access the placenta from hematogenous or decidual route. Finally, we highlight the challenges in studying human placental responses to pathogens and vertical transmission using current experimental models and identify gaps in knowledge that need to be addressed. We further propose novel experimental strategies to address such limitations.
Topics: Animals; Decidua; Disease Models, Animal; Female; Humans; Immunity, Innate; Infections; Infectious Disease Transmission, Vertical; Placenta; Pregnancy
PubMed: 33013876
DOI: 10.3389/fimmu.2020.02070