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International Journal of Molecular... Oct 2023Crucial roles in embryo implantation and placentation in humans include the invasion of the maternal decidua by extravillous trophoblasts and the motile behavior of...
Crucial roles in embryo implantation and placentation in humans include the invasion of the maternal decidua by extravillous trophoblasts and the motile behavior of decidual endometrial stromal cells. The effects of the epidermal growth factor (EGF) and GnRH-II in the endometrium take part in early pregnancy. In the present study, we demonstrated the coaction of EGF- and GnRH-II-promoted motility of human decidual endometrial stromal cells, indicating the possible roles of EGF and GnRH-II in embryo implantation and early pregnancy. After obtaining informed consent, we obtained human decidual endometrial stromal cells from decidual tissues from normal pregnancies at 6 to 12 weeks of gestation in healthy women undergoing suction dilation and curettage. Cell motility was evaluated with invasion and migration assays. The mechanisms of EGF and GnRH-II were performed using real-time PCR and immunoblot analysis. The results showed that human decidual tissue and stromal cells expressed the EGF and GnRH-I receptors. GnRH-II-mediated cell motility was enhanced by EGF and was suppressed by the knockdown of the endogenous GnRH-I receptor and EGF receptor with siRNA, revealing that GnRH-II promoted the cell motility of human decidual endometrial stromal cells through the GnRH-I receptor and the activation of Twist and N-cadherin signaling. This new concept regarding the coaction of EGF- and GnRH-promoted cell motility suggests that EGF and GnRH-II potentially affect embryo implantation and the decidual programming of human pregnancy.
Topics: Female; Humans; Pregnancy; Cadherins; Cell Movement; Decidua; Endometrium; Epidermal Growth Factor; Gonadotropin-Releasing Hormone; Receptors, LHRH; Stromal Cells; Trophoblasts
PubMed: 37894950
DOI: 10.3390/ijms242015271 -
Journal of Veterinary Science Sep 2023Hystricomorpha rodents display a similar placentation model to humans. The present study was carried out considering the scarcity of information concerning the placental...
BACKGROUND
Hystricomorpha rodents display a similar placentation model to humans. The present study was carried out considering the scarcity of information concerning the placental development in agouti.
OBJECTIVE
Describe the microscopy of the placenta, subplacenta and yolk sac of agoutis in early pregnancy and report on the inversion of the yolk sac.
METHODS
Fifteen females between the 14-32 day of gestation were used following euthanasia. Gestational buttons were collected, fixed, processed, stained to optical microscopy or immunohistochemistry.
RESULTS
Chorioallantoic placenta (CP) ranged from conical to a half-sphere, as follows: from the 14 to 17 day, the CP displays an inverted "V" shape, predominantly formed by cytotrophoblasts; from 20 to 22 days, formed almost entirely by cytotrophoblasts; at 28 days, a half sphere, with distinct lobes and interlobular area, numerous maternal gaps delimited by syncytiotrophoblasts and trophoblast giant cells; at 32 days, globose and undergoing the maturation process. Subplacenta, located between decidua and CP, initially presents septa consisting of simple columnar epithelium and after 17 days, comprising stratified epithelium. Visceral yolk sac (VYS) is attached to two CP projections between 14 and 17 days, formed by a simple cubic epithelium and inverted. Between 20 and 22 days, the epithelium displays apical villous projections with cytoplasmic vacuoles and a vascularized mesoderm. After the 24 day, the VYS near the placenta is pleated, very vascularized and villous, with decreased villi sizes further away from the placenta.
CONCLUSION
The agouti CP displays similar characteristics to other hystricomorpha, including placenta lobulation, a subplacenta and an inverted vitelline placenta.
Topics: Pregnancy; Female; Animals; Humans; Placentation; Placenta; Dasyproctidae; Rodentia; Yolk Sac
PubMed: 38031643
DOI: 10.4142/jvs.22323 -
Toxins Nov 2023is a notorious zoonotic disease caused by , which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS)...
is a notorious zoonotic disease caused by , which can lead to reproductive diseases in humans and animals, such as infertility and abortion. Lipopolysaccharides (LPS) are the main virulence factor of . LPS derived from are different and non-classical and are less toxic and less active than LPS isolated from However, the effects and possible mechanisms of LPS-caused pregnancy loss remain to be revealed. In the present study, we investigated the effects of S2 LPS on early pregnancy loss in mice. The results indicated that embryo implantation failure was induced by LPS treatment in a dose-dependent manner. The injection of LPS mainly resulted in fibrinolysis in the decidual area of the uterus on the 6th day post coition (dpc), infiltration of large granular cells among the decidual cells near the embryo on the 8th dpc, a large number of gaps in the decidual area, and cell necrosis around the embryo. In addition, the expression of Cyclin D3 mRNA in the uterus on the 7th and 8th dpc and IGFBP-1 mRNA and the progesterone receptor in the uterus on the 6th and 7th dpc were also inhibited. Moreover, the expression of decidualization marker Cyclin D3 and decidualization prolactin-associated protein (dPRP) in endometrial stromal cells were also inhibited by LPS treatment in vitro. In summary, LPS affect the process of endometrial decidualization in mice by affecting the structure of the decidua and the expression of decidual marker factors in endometrial stromal cells.
Topics: Pregnancy; Humans; Female; Mice; Animals; Decidua; Lipopolysaccharides; Brucella suis; Cyclin D3; Escherichia coli; Uterus; RNA, Messenger
PubMed: 37999525
DOI: 10.3390/toxins15110662 -
Cells Jan 2024(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and...
(1) Background: Inflammatory responses are implicated in embryo implantation, decidualization, pregnancy maintenance and labor. Both embryo implantation and decidualization are essential to successful pregnancy in rodents and primates. S100A6 is involved in inflammation, tumor development, apoptosis and calcium homeostasis. S100A6 is strongly expressed in mouse decidua, but the underlying mechanisms of how S100A6 regulates implantation and decidualization are poorly defined. (2) Methods: Mouse endometrial stromal and epithelial cells are isolated from day 4 pseudopregnant mouse uteri. Both immunofluorescence and Western blotting are used to analyze the expression and localization of proteins. The molecular mechanism is verified in vitro by Western blotting and the quantitative polymerase chain reaction. (3) Results: From days 4 to 8 of pregnancy, S100A6 is specifically expressed in mouse subluminal stromal cells. Blastocyst-derived lactic acid induces AA secretion by activating the luminal epithelial p-cPLA2. The epithelial AA induces stromal S100A6 expression through the COX2/PGI2/PPAR δ pathway. Progesterone regulates S100A6 expression through the progesterone receptor (PR). S100A6/RAGE signaling can regulate decidualization via EGFR/ERK1/2 in vitro. (4) Conclusions: S100A6, as an inflammatory mediator, is important for mouse implantation and decidualization.
Topics: Pregnancy; Female; Animals; Mice; Decidua; Arachidonic Acid; Uterus; Embryo Implantation; Blastocyst
PubMed: 38334598
DOI: 10.3390/cells13030206 -
Journal of Advanced Research Feb 2024Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are...
INTRODUCTION
Advanced maternal age is associated with reduced implantation and pregnancy rates, yet the underlying mechanisms remain poorly understood, and research models are limited.
OBJECTIVES
Here, we aim to elucidate the impacts of senescence on implantation ability by employing blastoids to construct a novel research model.
METHODS
We used a novel three-dimensional system with totipotent blastomere-like cells (TBLCs) to construct TBL-blastoids and established senescence-related embryo models derived from oxidative stress-induced TBLCs.
RESULTS
Morphological and transcriptomic analyses revealed that TBL-blastoids exhibited characteristic blastocyst morphology, cell lineages, and a higher consistency in developmental rate. TBL-blastoids demonstrated the ability to develop into postimplantation structures in vitro and successfully implanted into mouse uteri, inducing decidualization and forming embryonic tissues. Importantly, senescence impaired the implantation potential of TBL-blastoids, effectively mimicking the impaired implantation ability and reduced pregnancy rates associated with advanced age. Furthermore, analysis of differentially expressed genes (DEGs) in human homologous deciduae revealed enrichment in multiple fertility-related diseases and other complications of pregnancy. The genes implicated in these diseases and the common DEGs identified in the lineage-like cells of the two types of TBL-blastoids and deciduae may represent potential targets for addressing impaired implantation potential.
CONCLUSION
These results unveiled that TBL blastoids are an improved model for investigating implantation and early postimplantation, offering valuable insights into pregnancy-related disorders in women with advanced age and potential targets for therapeutic interventions.
PubMed: 38402947
DOI: 10.1016/j.jare.2024.02.011 -
Epigenetics Dec 2024Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from...
Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased expression. Increased expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; Decidua; DNA Methylation; Macrophages; Phagocytosis; Up-Regulation
PubMed: 38564758
DOI: 10.1080/15592294.2024.2337087 -
STAR Protocols Sep 2023Mesenchymal stem cells (MSCs), also referred to as "medicinal signaling cells," have gained prominence as candidates for cell-based therapy and in clinical trials owing...
Mesenchymal stem cells (MSCs), also referred to as "medicinal signaling cells," have gained prominence as candidates for cell-based therapy and in clinical trials owing to their regenerative and therapeutic properties. Here, we present a protocol for isolating MSCs from the decidua basalis layer of human placenta using an explant culture approach. We describe steps for collecting, disinfecting, and plating placental tissue. We then detail procedures for characterizing the isolated MSCs through flow cytometry and in vitro differentiation.
Topics: Humans; Pregnancy; Female; Placenta; Decidua; Mesenchymal Stem Cells; Flow Cytometry; Cell Differentiation
PubMed: 37573500
DOI: 10.1016/j.xpro.2023.102498 -
International Immunopharmacology Dec 2023Preeclampsia (PE) is a serious complication of pregnancy. Decidual natural killer (dNK) cells were reported to participate in the remodeling of spiral arteries through...
Preeclampsia (PE) is a serious complication of pregnancy. Decidual natural killer (dNK) cells were reported to participate in the remodeling of spiral arteries through producing a group of cytokines, including granulocyte-macrophage colony stimulating factor (GM-CSF). KIR2DS5 is an activating receptor of NK cells that specifically recognizes HLA-C2 on trophoblasts. Currently, there are no reports regarding the precise mechanism of KIR2DS5 in PE. This study included 30 PE patients and 30 healthy pregnant women. We found that the expressions of KIR2DS5 were significantly lower in PE deciduae compared to those of healthy pregnancies. By transfecting knockdown and overexpression lentivirus vectors of KIR2DS5 into dNK cells isolated from deciduae of early pregnancy, we altered the KIR2DS5 expression level in dNK cells. Then, these dNK cells and trophoblast cell lines were co-cultured as trophoblast-dNK cells. In the trophoblast-dNK cells, we examined the influence of KIR2DS5 on the biological manifestations of trophoblasts. As anticipated, overexpression of KIR2DS5 could facilitate cell proliferation, migration, and invasion. Furthermore, increased expression of KIR2DS5 inhibited cell apoptosis and enhanced the progression of cells from theG1 to theS stage. Further mechanistic study demonstrated a positive relationship between KIR2DS5 and GM-CSF in trophoblast-dNK cells. Accordingly, our observations indicated that a decrease in KIR2DS5 could reduce the expression of GM-CSF via the JAK2/STAT5 pathway, resulting in the failure of the activated signal to be transmitted to dNK cells and ultimately leading to the occurrence of PE. KIR2DS5 may be a new contributor for the prediction and diagnosis of PE.
Topics: Pregnancy; Female; Humans; Decidua; Granulocyte-Macrophage Colony-Stimulating Factor; Pre-Eclampsia; Cell Line; Killer Cells, Natural; Receptors, KIR
PubMed: 37864908
DOI: 10.1016/j.intimp.2023.111087 -
Frontiers in Cell and Developmental... 2024Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive...
Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). We performed this cohort study on patients receiving fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. All of these results reveal EDCs may disrupt female reproduction.
PubMed: 38887521
DOI: 10.3389/fcell.2024.1335028 -
Pacific Symposium on Biocomputing.... 2024Existing proposed pathogenesis for preeclampsia (PE) was only applied for early onset subtype and did not consider pre-pregnancy and competing risks. We aimed to...
BACKGROUND
Existing proposed pathogenesis for preeclampsia (PE) was only applied for early onset subtype and did not consider pre-pregnancy and competing risks. We aimed to decipher PE subtypes by identifying related transcriptome that represents endometrial maturation and histologic chorioamnionitis.
METHODS
We utilized eight arrays of mRNA expression for discovery (n=289), and other eight arrays for validation (n=352). Differentially expressed genes (DEGs) were overlapped between those of: (1) healthy samples from endometrium, decidua, and placenta, and placenta samples under histologic chorioamnionitis; and (2) placenta samples for each of the subtypes. They were all possible combinations based on four axes: (1) pregnancy-induced hypertension; (2) placental dysfunction-related diseases (e.g., fetal growth restriction [FGR]); (3) onset; and (4) severity.
RESULTS
The DEGs of endometrium at late-secretory phase, but none of decidua, significantly overlapped with those of any subtypes with: (1) early onset (p-values ≤0.008); (2) severe hypertension and proteinuria (p-values ≤0.042); or (3) chronic hypertension and/or severe PE with FGR (p-values ≤0.042). Although sharing the same subtypes whose DEGs with which significantly overlap, the gene regulation was mostly counter-expressed in placenta under chorioamnionitis (n=13/18, 72.22%; odds ratio [OR] upper bounds ≤0.21) but co-expressed in late-secretory endometrium (n=3/9, 66.67%; OR lower bounds ≥1.17). Neither the placental DEGs at first-nor second-trimester under normotensive pregnancy significantly overlapped with those under late-onset, severe PE without FGR.
CONCLUSIONS
We identified the transcriptome of endometrial maturation in placental dysfunction that distinguished early- and late-onset PE, and indicated chorioamnionitis as a PE competing risk. This study implied a feasibility to develop and validate the pathogenesis models that include pre-pregnancy and competing risks to decide if it is needed to collect prospective data for PE starting from pre-pregnancy including chorioamnionitis information.
Topics: Pregnancy; Female; Humans; Placenta; Transcriptome; Pre-Eclampsia; Chorioamnionitis; Prospective Studies; Computational Biology; Fetal Growth Retardation; Decidua; Hypertension
PubMed: 38160306
DOI: No ID Found