scholarly journals Spontaneous embryo resorption in the mouse is triggered by embryonic apoptosis followed by rapid removal via maternal sterile purulent inflammation

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Barbara Drews ◽  
Luis Flores Landaverde ◽  
Anja Kühl ◽  
Ulrich Drews

Abstract Background In normal mammalian development a high percentage of implantations is lost by spontaneous resorption. This is a major problem in assisted reproduction and blastocyst transfer. Which embryo will be resorbed is unpredictable. Resorption is very fast, so that with conventional methods only final haemorrhagic stages are encountered. Here we describe the histology and immunohistochemistry of 23 spontaneous embryo resorptions between days 7 and 13 of murine development, which were identified by high-resolution ultrasound (US) in a previous study. Results In the early resorptions detected at day 7, the embryo proper was replaced by maternal haemorrhage and a suppurate focus of maternal neutrophils. In the decidua maternal macrophages transformed to foam cells and formed a second focus of tissue dissolution. In the late resorptions detected at day 9, the embryo underwent apoptosis without involvement of maternal cells. The apoptotic embryonic cells expressed caspase 3 and embryonic blood cells developed a macrophage like phenotype. Subsequently, the wall of the embryonic vesicle ruptured and the apoptotic embryo was aborted into the uterine lumen. Abortion was initiated by degeneration of the embryonic lacunar trophoblast and dissolution of the maternal decidua capsularis via sterile inflammation and accompanied by maternal haemorrhage, invasion of the apoptotic embryo by maternal neutrophils, and contraction rings of the uterine muscle layers. Conclusions We conclude that spontaneous resorption starts with endogenous apoptosis of the embryo without maternal contribution. After break down of the foetal-maternal border, the apoptotic embryo is invaded by maternal neutrophils, aborted into the uterine lumen, and rapidly resorbed. We assume that the innate maternal unspecific inflammation is elicited by disintegrating apoptotic embryonic cells. Graphical abstract

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Giang Tong ◽  
Nalina N. A. von Garlen ◽  
Sylvia J. Wowro ◽  
Phuong D. Lam ◽  
Jana Krech ◽  
...  

Introduction. Fever is frequently observed after acute ischemic events and is associated with poor outcome and higher mortality. Targeted temperature management (TTM) is recommended for neuroprotection in comatose cardiac arrest survivors, but pyrexia after rewarming is proven to be detrimental in clinical trials. However, the cellular mechanisms and kinetics of post-TTM rebound pyrexia remain to be elucidated. Therefore, we investigated the effects of cooling and post-TTM pyrexia on the inflammatory response and apoptosis in a cardiomyocyte ischemia-reperfusion (IR) injury model. Methods. HL-1 cardiomyocytes were divided into the following groups to investigate the effect of oxygen-glucose deprivation/reperfusion (OGD/R), hypothermia (33.5°C), and pyrexia (40°C): normoxia controls maintained at 37°C and warmed to 40°C, OGD/R groups maintained at 37°C and cooled to 33.5°C for 24 h with rewarming to 37°C, and OGD/R pyrexia groups further warmed from 37 to 40°C. Caspase-3 and RBM3 were assessed by Western blot and TNF-α, IL-6, IL-1β, SOCS3, iNOS, and RBM3 transcriptions by RT-qPCR. Results. OGD-induced oxidative stress (iNOS) in cardiomyocytes was attenuated post-TTM by cooling. Cytokine transcriptions were suppressed by OGD, while reperfusion induced significant TNF-α transcription that was exacerbated by cooling. Significant inductions of TNF-α, IL-6, IL-1β, and SOCS3 were observed in noncooled, but not in cooled and rewarmed, OGD/R-injured cardiomyocytes. Further warming to pyrexia induced a sterile inflammatory response in OGD/R-injured groups that was attenuated by previous cooling, but no inflammation was observed in pyrexic normoxia groups. Moreover, cytoprotective RBM3 expression was induced by cooling but suppressed by pyrexia, correlating with apoptotic caspase-3 activation. Conclusion. Our findings show that maintaining a period of post-TTM “therapeutic normothermia” is effective in preventing secondary apoptosis-driven myocardial cell death, thus minimizing the infarct area and further release of mediators of the innate sterile inflammatory response after acute IR injury.


Author(s):  
Lincoln V. Johnson ◽  
Patricia G. Calarco ◽  
Syivia Ploack-Charcon

Cell surface molecules are known to be functionally important In a number of developmental systems. Molecular components of the cell surface may participate in Intercellular adhesion, recognition and communication. Reactions occur r Ing at the cell surface may also influence developmental events by Induci ng i ntracelIular changes In cellular metabolism and gene expression which may, In turn, alter the composition and/or organization of surface components. Sequences of reactions mediated by cell surface molecules are probably Important In directing undifferentiated embryonic cells along specific dlfferentlatlve pathways.In the early development of the mammal Ian embryo, important events occurring during the preimplantation period are likely to require the participation of specific cell surface molecules. For example, these are likely to Include sperm-egg attachment and fusion, Interbl astomere adhesion, blastulatlon, and attachment of the blastocyst to the uterine epithelium. During preimplantation mouse development, specific stage-relaged changes in the qual itatlve and quantitative nature of the proteins synthesized and those expressed on the cell surface have been documented.


2022 ◽  
Vol 67 (4) ◽  
pp. 376-381
Author(s):  
Milat Ismail Haje ◽  
Nazar P. Shabila

Freezing embryos is the best way to increase fertility for women with ovarian hyper-stimulation syndrome and women at risk for ovarian dysfunction. Due to the importance of freezing and pregnancy embryos, the present study was conducted to compare the fertility rate and the affecting factors following fresh embryos and frozen embryos in women treated with assisted reproductive techniques. In this study, 250 infertile women and IVF/ICSI candidates were studied. Embryos were used in fresh or frozen groups for transfer to the uterus. The expression of the caspase-3 gene was also examined for further evaluation. Data analysis was performed using SPSS 16 software, Chi-square, independent t-test, and Kruskal-Wallis tests. Out of 250 infertile women, 96 (38.4%) became pregnant, of which 54 were in the fresh embryo group and 42 were in the frozen embryo group, which was not statistically significant (P=0.32). Infertility causes, number of embryonic cells and grading of transferred embryos, delivery complications, embryo implantation methods, number of produced embryos after delivery, and endometrial thickness were not significantly different between the two groups (P=0.53). The difference between the mean number of transferred embryos in the two groups was significant (P<0.05), which was no longer significant after excluding non-pregnant women, and in comparing with only pregnant women (P=0.36). The result of caspase-3 gene expression showed that there was significant differences between fresh embryos, healthy thawed frozen embryos, and destroyed thawed frozen embryos. But these results were totally different from the results of the Pregnancy rate section. Therefore, it is inferred that although caspase-3 genes are expressed in frozen embryos after thawing and are ready to destroy the embryo, there are probably a number of involved factors that prevent the activity of caspase-3 and do not allow the apoptotic process to occur. What these factors are and how they prevent this process needs further study.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fabian A. Fischer ◽  
Kaiwen W. Chen ◽  
Jelena S. Bezbradica

Pyroptosis is a proinflammatory form of cell death, mediated by membrane pore-forming proteins called gasdermins. Gasdermin pores allow the release of the pro-inflammatory cytokines IL-1β and IL-18 and cause cell swelling and cell lysis leading to release of other intracellular proteins that act as alarmins to perpetuate inflammation. The best characterized, gasdermin D, forms pores via its N-terminal domain, generated after the cleavage of full length gasdermin D by caspase-1 or -11 (caspase-4/5 in humans) typically upon sensing of intracellular pathogens. Thus, gasdermins were originally thought to largely contribute to pathogen-induced inflammation. We now know that gasdermin family members can also be cleaved by other proteases, such as caspase-3, caspase-8 and granzymes, and that they contribute to sterile inflammation as well as inflammation in autoinflammatory diseases or during cancer immunotherapy. Here we briefly review how and when gasdermin pores are formed, and then focus on emerging endogenous mechanisms and therapeutic approaches that could be used to control pore formation, pyroptosis and downstream inflammation.


2021 ◽  
Vol 12 ◽  
pp. 204173142110003
Author(s):  
Thomas Später ◽  
Denise MS Worringer ◽  
Maximilian M Menger ◽  
Michael D Menger ◽  
Matthias W Laschke

Adipose tissue-derived microvascular fragments (MVF) are used as vascularization units in tissue engineering. In this study, we investigated whether the vascularization capacity of MVF can be improved by systemic low-dose erythropoietin (EPO) administration. MVF were isolated from the epididymal fat of donor mice and seeded onto collagen-glycosaminoglycan matrices, which were implanted into full-thickness skin defects within dorsal skinfold chambers of recipient mice. Both donor and recipient mice were treated daily with either EPO (500 IU/kg) or vehicle (0.9% NaCl). The implants were analyzed by stereomicroscopy, intravital fluorescence microscopy, histology, and immunohistochemistry. EPO-treated MVF contained a comparable number of proliferating Ki67+ but less apoptotic cleaved caspase-3+ endothelial cells when compared to vehicle-treated controls. Moreover, EPO treatment accelerated and improved the in vivo vascularization, blood vessel maturation, and epithelialization of MVF-seeded matrices. These findings indicate that systemic low-dose EPO treatment is suitable to enhance the viability and network-forming capacity of MVF.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
María H. Viotti ◽  
Pablo Juri ◽  
Paula Lombide ◽  
María L. Presentado ◽  
José M. Verdes ◽  
...  

Abstract Toxic honeydew produced by Flatidae Epormenis cestri in Uruguay has been shown to cause among honeybees (Apis mellifera) colonies a massive larva death called “River disease”, but the intrinsic mechanisms are still unknown. Because fat body cells, oenocytes and trophocytes, are known to regulated larvae metabolism, and to be affected by xenobiotics, we tested whether apoptosis of these cells can be an underlying cause of larvae death. Ten colonies were divided into two groups and fed with common honey or toxic honeydew obtained from colonies affected by “River disease”. Five-dayold larvae were collected and processed for histology and immunohistochemistry for caspase-3. The area, diameter, and immunostaining area in oenocytes and trophocytes were measured. The oenocyte and trophocyte cellular area decreased in the treated group (p=0.002; p<0.001 respectively) compared to the control group. The diameter of oenocytes (p=0.0002) and trophocytes (p<0.0001) decreased in the treated group. Caspase-3 was detected in cytoplasm in the control group but in the cytoplasm and nucleus in the treated group. The caspase-3 immunostaining area increased in oenocytes (p<0.002) and trophocytes (p<0.0001) of the treated group. The ingestion of toxic honeydew altered the morphology, localization and immunoexpression of caspase-3 in fat body cells, which suggests that the deregulation of the apoptotic mechanism affected the normal development in A. mellifera larvae.


1991 ◽  
Vol 113 (2) ◽  
pp. 437-449 ◽  
Author(s):  
C L Librach ◽  
Z Werb ◽  
M L Fitzgerald ◽  
K Chiu ◽  
N M Corwin ◽  
...  

The specialized interaction between embryonic and maternal tissues is unique to mammalian development. This interaction begins with invasion of the uterus by the first differentiated embryonic cells, the trophoblasts, and culminates in formation of the placenta. The transient tumor-like behavior of cytotrophoblasts, which peaks early in pregnancy, is developmentally regulated. Likewise, in culture only early-gestation human cytotrophoblasts invade a basement membrane-like substrate. These invasive cells synthesize both metalloproteinases and urokinase-type plasminogen activator. Metalloproteinase inhibitors and a function-perturbing antibody specific for the 92-kD type IV collagen-degrading metalloproteinase completely inhibited cytotrophoblast invasion, whereas inhibitors of the plasminogen activator system had only a partial (20-40%) inhibitory effect. We conclude that the 92-kD type IV collagenase is critical for cytotrophoblast invasion.


Author(s):  
L. V. Leak ◽  
J. F. Burke

The vital role played by the lymphatic capillaries in the transfer of tissue fluids and particulate materials from the connective tissue area can be demonstrated by the rapid removal of injected vital dyes into the tissue areas. In order to ascertain the mechanisms involved in the transfer of substances from the connective tissue area at the ultrastructural level, we have injected colloidal particles of varying sizes which range from 80 A up to 900-mμ. These colloidal particles (colloidal ferritin 80-100A, thorium dioxide 100-200 A, biological carbon 200-300 and latex spheres 900-mμ) are injected directly into the interstitial spaces of the connective tissue with glass micro-needles mounted in a modified Chambers micromanipulator. The progress of the particles from the interstitial space into the lymphatic capillary lumen is followed by observing tissues from animals (skin of the guinea pig ear) that were injected at various time intervals ranging from 5 minutes up to 6 months.


Author(s):  
J. Holy ◽  
G. Schatten

One of the classic limitations of light microscopy has been the fact that three dimensional biological events could only be visualized in two dimensions. Recently, this shortcoming has been overcome by combining the technologies of laser scanning confocal microscopy (LSCM) and computer processing of microscopical data by volume rendering methods. We have employed these techniques to examine morphogenetic events characterizing early development of sea urchin embryos. Specifically, the fourth cleavage division was examined because it is at this point that the first morphological signs of cell differentiation appear, manifested in the production of macromeres and micromeres by unequally dividing vegetal blastomeres.The mitotic spindle within vegetal blastomeres undergoing unequal cleavage are highly polarized and develop specialized, flattened asters toward the micromere pole. In order to reconstruct the three-dimensional features of these spindles, both isolated spindles and intact, extracted embryos were fluorescently labeled with antibodies directed against either centrosomes or tubulin.


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