scholarly journals Single Cell Proteomics Profiling Revealing that Embryo Secreted TNF-α play Critical Role during Embryo Implantation to Endometrium

2020 ◽  
Author(s):  
Lv Jiao ◽  
Shan Xudong ◽  
Yang Haoxuan ◽  
Wen Yuting ◽  
Zhang Xueguang ◽  
...  
Keyword(s):  
Single Cell ◽  
Embryo Quality ◽  
Embryo Implantation ◽  
Critical Role ◽  
Cell Mass ◽  
Gene Profiling ◽  
Immunofluorescence Staining ◽  
Tunel Staining ◽  
Implantation Failure ◽  
Tnf Α

Abstract Problem: Although it has long been known that endometrium secreted cytokines play critical role during embryo implantation, whether cytokines secreted from embryo is relevant to embryo quality and is actively involved in embryo attachment remain unclear.Method of study: The concentration of cytokines in embryo culture medium were tested by a new developed high-sensitive single cell proteomic platform, compared with embryo quality and clinical outcome. The effect of TNF-α on embryo and endometrium Ishikawa cell was investigated using immunofluorescence staining, CCK- 8 assay, TUNEL staining, and RT-qPCR reaction.Results: Of the 10 cytokines measured, only TNF-α concentration is significantly higher in group of embryo implantation failure. Immunofluorescence staining showed that the expression of TNF-α was unevenly distributed in blastocysts, and the expression level was significantly correlated with blastocysts inner cell mass (ICM) quality score. Adding TNF-α caused significant increase of apoptotic cells, which could be inhibited by TNF-α receptor blocker entanecept (ETA). Gene profiling showed that adding TNF-α lead to increased expression of TNFR1 and apoptosis related genes, as well as ion channel genes, including CFTR, ENaCA, AQP3 and CRISP2, and the increase can be inhibited by ETA. Conclusion: In conclusion, our result showed that higher TNF-α level is associated with implantation failure through activation of TNF-α receptor, and TNF-α maybe an independent predictor for pre-transfer assessment of the embryo development potential in IVF patients.

scholarly journals Single cell proteomics profiling reveals that embryo-secreted TNF-α plays a critical role during embryo implantation to the endometrium

2020 ◽  
Author(s):  
Lv Jiao ◽  
Xudong Shan ◽  
Haoxuan Yang ◽  
Yuting Wen ◽  
Xueguang Zhang ◽  
...  
Keyword(s):  
Single Cell ◽  
Inner Cell Mass ◽  
Embryo Implantation ◽  
Critical Role ◽  
Cell Mass ◽  
Gene Profiling ◽  
Immunofluorescence Staining ◽  
Tunel Staining ◽  
Implantation Failure ◽  
Tnf Α

Abstract Background It has been long-known that endometrium-secreted cytokines play a critical role during embryo implantation. However, whether cytokines secreted from the embryo are relevant to the process of embryo implantation remains unclear. Methods The concentration of cytokines in embryo culture medium was tested using a newly developed, high-sensitivity single-cell proteomic platform and evaluated in comparison to embryo quality and clinical outcome. The effect of TNF-α on embryo and endometrium Ishikawa cells was investigated using immunofluorescence staining, CCK- 8 assay, TUNEL staining, and RT-qPCR. Results Of the 10 cytokines measured, only TNF-α concentration was significantly higher in the group with embryo implantation failure. Immunofluorescence staining showed that the expression of TNF-α was unevenly distributed in blastocysts, and the expression level was significantly correlated with the blastocyst inner cell mass (ICM) quality score. Gene profiling showed that addition of TNF-α led to increased expression of tumor necrosis factor receptor 1 (TNFR1) and apoptosis-related genes and that this could be inhibited by the TNF-α receptor inhibitor entanecept (ETA). In addition, an increased expression of water and ion channels, including AQP3, CFTR, ENaCA and CRISP2 was also observed which could also be inhibited by ETA. Conclusions Our results show that higher embryo-secreted TNF-α levels are associated with implantation failure through activation of TNF-α receptor, and TNF-α may be an independent predictor for pre-transfer assessment of the embryo development potential in IVF patients.

The Mechanism of Rhein Ameliorating the Survival Rate of Transplanted Mesenchymal Stem Cells by Improving Myocardial Microenvironment in Acute Myocardial Infarction

2021 ◽  
Vol 11 (4) ◽  
pp. 684-689
Author(s):  
Xuejun Deng ◽  
Xiaojun He ◽  
Gang Huang ◽  
Dongmei Yu ◽  
Xiaozhen Lin
Keyword(s):  
Myocardial Infarction ◽  
Stem Cells ◽  
Survival Rate ◽  
Heart Function ◽  
Immunofluorescence Staining ◽  
Inflammatory Factors ◽  
Tunel Staining ◽  
Myocardial Tissue ◽  
Tnf Α ◽  
Myocardial Fibers

Background: The paper investigated the mechanism of Rhein improving the ischemic myocardial microenvironment, promoting the survival rate of transplanted BMSCs and functional recovery of damaged myocardium by alleviating myocardial ERS-mediated hyperinflammation and apoptosis after AMI. Material and Methods: A model of myocardial infarction was established. BLI was used to detect the survival rate of transplanted stem cells at 1, 7, 14, 21 and 28 days after surgery. TUNEL staining was used to assess apoptosis. ERS-related protein CHOP immunofluorescence staining was used to assess ERS level. The expressions of ERS-related biomarkers ATF4, CHOP, GRP78 and GRP94 were detected by Western Blot. The inflammatory factors IL-6, TNF-α and IL- 10 of myocardial tissue were detected by ELISA. CD31 immunization was performed 28 days after surgery. Fluorescence staining was used to assess tissue angiogenesis. Results: Rhein combined with BMSCs could improve cardiac function, decrease apoptosis and myocardial CHOP expression. WB showed that the expressions of ATF4, CHOP, GRP78 and GRP94 in myocardial tissue of MI rats were decreased. ELISA showed that Rhein can inhibit the expressions of pro-inflammatory factors IL-6 and TNF-α, and promote anti-inflammatory factors IL-10 expression. CD31 immunofluorescence staining showed that Rhein can promote the formation of neovascularization in infarcted myocardium. Conclusion: In AMI, myocardial ERS is activated. Rhein inhibits ERS and the mediated inflammation and oxidative stress after AMI, inhibits apoptosis, improves the survival rate of transplanted BMSCs, enhances BMSCs to promote neovascularization, inhibits myocardial fibers, and improves heart function.

scholarly journals Implantation Failure in Female Kiss1−/− Mice Is Independent of Their Hypogonadic State and Can Be Partially Rescued by Leukemia Inhibitory Factor

Endocrinology ◽  
2014 ◽  
Vol 155 (8) ◽  
pp. 3065-3078 ◽  
Author(s):  
Michele Calder ◽  
Yee-Ming Chan ◽  
Renju Raj ◽  
Macarena Pampillo ◽  
Adrienne Elbert ◽  
...  
Keyword(s):  
Leukemia Inhibitory Factor ◽  
Hypogonadotropic Hypogonadism ◽  
Embryo Implantation ◽  
Critical Role ◽  
Inhibitory Factor ◽  
Implantation Failure ◽  
Mouse Uterus ◽  
Female Mice ◽  
Wild Type Female ◽  
Neuroendocrine Axis

The hypothalamic kisspeptin signaling system is a major positive regulator of the reproductive neuroendocrine axis, and loss of Kiss1 in the mouse results in infertility, a condition generally attributed to its hypogonadotropic hypogonadism. We demonstrate that in Kiss1−/− female mice, acute replacement of gonadotropins and estradiol restores ovulation, mating, and fertilization; however, these mice are still unable to achieve pregnancy because embryos fail to implant. Progesterone treatment did not overcome this defect. Kiss1+/− embryos transferred to a wild-type female mouse can successfully implant, demonstrating the defect is due to maternal factors. Kisspeptin and its receptor are expressed in the mouse uterus, and we suggest that it is the absence of uterine kisspeptin signaling that underlies the implantation failure. This absence, however, does not prevent the closure of the uterine implantation chamber, proper alignment of the embryo, and the ability of the uterus to undergo decidualization. Instead, the loss of Kiss1 expression specifically disrupts embryo attachment to the uterus. We observed that on the day of implantation, leukemia inhibitory factor (Lif), a cytokine that is absolutely required for implantation in mice, is weakly expressed in Kiss1−/− uterine glands and that the administration of exogenous Lif to hormone-primed Kiss1−/− female mice is sufficient to partially rescue implantation. Taken together, our study reveals that uterine kisspeptin signaling regulates glandular Lif levels, thereby identifying a novel and critical role for kisspeptin in regulating embryo implantation in the mouse. This study provides compelling reasons to explore this role in other species, particularly livestock and humans.

scholarly journals Tumor susceptibility gene 101 is required for the maintenance of uterine epithelial cells during embryo implantation

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hyunji Byun ◽  
Sojung Kwon ◽  
Kay-Uwe Wagner ◽  
Hyejin Shin ◽  
Hyunjung Jade Lim
Keyword(s):  
Epithelial Cells ◽  
Embryo Implantation ◽  
Susceptibility Gene ◽  
Normal Pregnancy ◽  
Uterine Epithelium ◽  
Immunofluorescence Staining ◽  
Implantation Failure ◽  
Uterine Epithelial Cells ◽  
Tumor Susceptibility ◽  
Tumor Susceptibility Gene

Abstract Background The tumor susceptibility gene 101 (Tsg101), a component of the endosomal sorting complex required for transport (ESCRT) complex I, is involved in multiple biological processes involving endomembranous structures and the plasma membrane. The role of Tsg101 in the uterine epithelium was investigated in Tsg101 floxed mice crossed with Lactoferrin-iCre mice (Tsg101d/d). Methods Tsg101d/d mice were bred with stud male mice and the status of pregnancy was examined on days 4 and 6. Histological analyses were performed to examine the uterine architecture. Immunofluorescence staining of several markers was examined by confocal microscopy. Uterine epithelial cells (UECs) were isolated from Tsg101f/f and Tsg101d/d mice, and the expression of necroptosis effectors was examined by RT-PCR, western blotting, and immunofluorescence staining. UECs were also subjected to RNA expression profiling. Results Tsg101d/d female mice were subfertile with implantation failure, showing unattached blastocysts on day 6 of pregnancy. Histological and marker analyses revealed that some Tsg101d/d day 4 pregnant uteri showed a disintegrated uterine epithelial structure. Tsg101d/d UECs began to degenerate within 18 h of culture. In UECs, expression of necroptosis effectors, such as RIPK1, RIPK3, and MLKL were first confirmed. UECs responded to a stimulus to activate necroptosis and showed increased cell death. Conclusions Tsg101 deficiency in the uterine epithelium causes implantation failure, which may be caused by epithelial defects. This study provides evidence that UECs harbor a necroptotic machinery that responds to death-inducing signals. Thus, Tsg101 expression in the uterine epithelium is required for normal pregnancy in mice.

Tumor Susceptibility Gene 101 Is Required for the Maintenance of Uterine Epithelial Cells During Embryo Implantation

2021 ◽  
Author(s):  
Hyunji Byun ◽  
Sojung Kwon ◽  
Kay-Uwe Wagner ◽  
Hyejin Shin ◽  
Hyunjung Jade Lim
Keyword(s):  
Epithelial Cells ◽  
Embryo Implantation ◽  
Susceptibility Gene ◽  
Normal Pregnancy ◽  
Uterine Epithelium ◽  
Immunofluorescence Staining ◽  
Implantation Failure ◽  
Uterine Epithelial Cells ◽  
Tumor Susceptibility ◽  
Tumor Susceptibility Gene

Abstract Background: The tumor susceptibility gene 101 (Tsg101), a component of the endosomal sorting complex required for transport (ESCRT) complex I, is involved in multiple biological processes involving endomembranous structures and the plasma membrane. The role of Tsg101 in the uterine epithelium was investigated in Tsg101 floxed mice crossed with Lactoferrin-iCre mice (Tsg101d/d).Methods: Tsg101d/d mice were bred with stud male mice and the status of pregnancy was examined on days 4 and 6. Histological analyses were performed to examine the uterine architecture. Immunofluorescence staining of several markers was examined by confocal microscopy. Uterine epithelial cells (UECs) were isolated from Tsg101f/f and Tsg101d/d mice, and the expression of necroptosis effectors was examined by RT-PCR, western blotting, and immunofluorescence staining. UECs were also subjected to RNA expression profiling.Results: Tsg101d/d female mice were subfertile with implantation failure, showing unattached blastocysts on day 6 of pregnancy. Histological and marker analyses revealed that some Tsg101d/d day 4 pregnant uteri showed a disintegrated uterine epithelial structure. Tsg101d/d UECs began to degenerate within 18 h of culture. In UECs, expression of necroptosis effectors, such as RIPK1, RIPK3, and MLKL were first confirmed. UECs responded to a stimulus to activate necroptosis and showed increased cell death. Conclusions: Tsg101 deficiency in the uterine epithelium causes implantation failure, which accompanies epithelial defects. This study provides evidence that UECs harbor a necroptotic machinery that responds to death-inducing signals. Thus, Tsg101 expression in the uterine epithelium is required for normal pregnancy in mice.

scholarly journals Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation

2021 ◽  
Vol 15 (1) ◽  
pp. 53
Author(s):  
Hyerin Park ◽  
Minkyoung Cho ◽  
Yoonju Do ◽  
Jang-Kyung Park ◽  
Sung-Jin Bae ◽  
...  
Keyword(s):  
Natural Products ◽  
Embryo Quality ◽  
Embryo Implantation ◽  
Prenatal Development ◽  
Endometrial Receptivity ◽  
Female Infertility ◽  
Implantation Failure ◽  
Comprehensive Understanding ◽  
New Treatment ◽  
The Relationship

Infertility is an emerging health issue worldwide, and female infertility is intimately associated with embryo implantation failure. Embryo implantation is an essential process during the initiation of prenatal development. Recent studies have strongly suggested that autophagy in the endometrium is the most important factor for successful embryo implantation. In addition, several studies have reported the effects of various natural products on infertility improvement via the regulation of embryo implantation, embryo quality, and endometrial receptivity. However, it is unclear whether natural products can improve embryo implantation ability by regulating endometrial autophagy. Therefore, we performed a literature review of studies on endometrial autophagy, embryo implantation, natural products, and female infertility. Based on the information from these studies, this review suggests a new treatment strategy for female infertility by proposing natural products that have been proven to be safe and effective as endometrial autophagy regulators; additionally, we provide a comprehensive understanding of the relationship between the regulation of endometrial autophagy by natural products and female infertility, with an emphasis on embryo implantation.

Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

2019 ◽  
Vol 133 (22) ◽  
pp. 2283-2299
Author(s):  
Apabrita Ayan Das ◽  
Devasmita Chakravarty ◽  
Debmalya Bhunia ◽  
Surajit Ghosh ◽  
Prakash C. Mandal ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Chronic Inflammation ◽  
Ex Vivo ◽  
Human Subjects ◽  
Critical Role ◽  
Atherosclerotic Cardiovascular Disease ◽  
Tnf Α ◽  
Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

scholarly journals Role of Vascular Endothelial Growth Factor (VEGF) in Human Embryo Implantation: Clinical Implications

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 253
Author(s):  
Xi Guo ◽  
Hong Yi ◽  
Tin Chiu Li ◽  
Yu Wang ◽  
Huilin Wang ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Recurrent Miscarriage ◽  
Embryo Implantation ◽  
Critical Role ◽  
Angiogenic Factor ◽  
Vascular Endothelial ◽  
Underlying Mechanisms ◽  
Endothelial Growth Factor

Vascular endothelial growth factor (VEGF) is a well-known angiogenic factor that plays a critical role in various physiological and pathological processes. VEGF also contributes to the process of embryo implantation by enhancing embryo development, improving endometrial receptivity, and facilitating the interactions between the developing embryo and the endometrium. There is a correlation between the alteration of VEGF expression and reproductive failure, including recurrent implantation failure (RIF) and recurrent miscarriage (RM). In order to clarify the role of VEGF in embryo implantation, we reviewed recent literature concerning the expression and function of VEGF in the reproductive system around the time of embryo implantation and we provide a summary of the findings reported so far. We also explored the effects and the possible underlying mechanisms of action of VEGF in embryo implantation.

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