Are the cytokines TNF alpha and IL 1Beta early predictors of embryo implantation? Cross sectional study

Salama, Khalid M.; Alloush, M.K.; hussini, Reham M. Al

doi:10.1016/j.jri.2019.102618

Cited by 21 publications

(22 citation statements)

References 35 publications

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“…We observed that the supplementation of IL-1β to cultured embryos increased blastocyst hatching percentage, accompanied by accelerated hatching by 24 h. This hatching accelerating effect observed with the IL-1β-supplemented embryos is very significant, since in vitro cultured mammalian embryos normally show a substantial delay in blastocyst development, compared to their in vivo counterparts (Harlow & Quinn 1982, Roth et al 1994, Stokes et al 2005, Lange-Consiglio et al 2020. Of relevance, here, is the recent report which showed an increased IL-1β in cultured human embryos and it is considered as an early predictor of a successful pregnancy (Salama et al 2020). Taken together, it appears that IL-1β is important for improved development and hatching of blastocysts in humans and in other mammalian species as well.…”

Section: Discussionmentioning

confidence: 80%

“…This study shows, for the first time, the involvement of IL-1β in the development-hatching of blastocysts and in modulating the hatching-associated proteases, that is, ISP 1 and ISP 2 in the mouse. Earlier, the role of IL-1β during embryo implantation and in maintaining viable pregnancy was reported in the mouse (Sequeira et al 2015, Salama et al 2020 as well as in the human (Kruessel et al 1997, von Wolff et al 2000, Salama et al 2020. But, there were also contradictory reports indicating that the IL-1β is not an essential requirement during the implantation process owing, to other cytokines' functional redundancy, with overlapping signaling occurring in vivo (Abbondanzo et al 1996, Stewart & Cullinan 1997.…”

Section: Discussionmentioning

confidence: 99%

“…In humans, both the embryo and the endometrium express IL-1β and its increasing concentration is associated with successful implantation. In this regard, IL-1β is thought to be a potent embryo biomarker for successful implantation (Sequeira et al 2015, Salama et al 2020. Moreover, the embryonic expression of IL-1ra cytokine, the natural antagonist of IL-1β, has been shown to be associated with developmentally arrested embryos (Kruessel et al 1997.…”

Section: Introductionmentioning

confidence: 99%

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Expression of IL-1β and implantation serine proteases is required for mouse blastocyst hatching

et al. 2021

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Mammalian blastocyst hatching is critically an indispensable process for successful implantation. One of the major challenges in IVF clinics is to achieve superior embryonic development with intrinsically potent hatching-competent blastocyst. However, the molecular regulation of hatching phenomenon is poorly understood. In this study, we examined the expression and function of one of the cytokines, IL-1β during blastocyst hatching in the mouse. In particular, the expression of IL-1β (Interleukin-1β), IL-1ra (Interleukin-1 receptor antagonist) and their functional receptor IL-1rt1 (Interleukin 1 receptor type-1) in morulae, zona intact- and hatched- blastocysts was studied. Supplementation of IL-1β to cultured embryos accelerated blastocyst development with improved hatching (treated: 89.6 ± 3.6% vs untreated: 65.4 ± 4.1%). When embryos were treated with IL-1ra, blastocyst hatching was decreased (treated: 28.8 ± 3.1% vs untreated: 67.5 ± 3.8%). Moreover, IL-1β and IL-1ra influenced the expression of hatching enzymes viz., implantation serine proteases (ISP 1 and ISP 2). While IL-1β increased the embryonic mRNA expression of ISPs (ISP1: 2-4; ISP2: 9-11 fold), IL-1ra decreased expression. The protein localization studies revealed increased nuclear presence predominantly of ISP 2 in IL-1β treated blastocysts. This is the first report to show the functional significance of embryonic IL-1β in regulating hatching-associated proteases, particularly ISP2. These findings have implications in our understanding of molecular regulation of blastocyst hatching and implantation failure in other species including humans.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of IL-1β and implantation serine proteases is required for mouse blastocyst hatching

et al. 2021

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“…According to Salam et al, TNF-α regulates the trophoblastic metalloproteinases MMP-2, MMP3 and MMP-9, which enable trophoblast invasion. A higher TNF–α level was associated with a higher pregnancy rate, and it was established that the determination of TNF-α concentration might be a useful tool to predict embryo implantation [ 41 ]. Similarly, our RPL patients had a lower level of TNF-α than fertile women, which might be related to the incorrect implantation process [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Kniotek

Zych

Roszczyk

et al. 2021

JCM

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Sildenafil citrate (SC), a PDE5 inhibitor, a drug for erectile dysfunction (ED) and pulmonary hypertension (PAH), was found to exert a positive effect on pregnancy outcomes when administered intravaginally before conception. In our previous studies, sildenafil increased endometrial thickness and significantly decreased peripheral blood NK cell activity after the intravaginal administration in women with recurrent pregnancy loss (RPL). No data are available to confirm the effect of sildenafil on maternal T cell populations involved in shaping fetal-maternal tolerance and NK cell activity. Thus, the present study aimed to establish if SC influences NKT cells or the axis of Th17/Treg cells and Th1/Th2 cytokine production. Materials and methods: Twenty-one healthy fertile women and twenty-two nonpregnant women with idiopathic RPL were studied. The ELISA method was used to evaluate the production of cytokines, including IL-2, IL-12p40, IL-4, IL-10, IL-6, IL-17, IL-21, TGF-β, TNF-α, and IFN-γ in PBMC culture supernatants before and after supplementation with the physiological concentration of SC. The percentages of NKT (CD56+CD3+CD44+CD161+), Treg (CD4+CD25+FOXP3+) and Th17 (CD4+CD25+IL-17A+) cells were determined with flow cytometry method. Results: Unexpectedly, we found that the PBMCs of patients with RPL produced a significantly lower level of inflammatory cytokines (TNF-α and IL-6) and a higher level of anti-inflammatory cytokines (TGF-β and IL-10). SC significantly decreased IL-6, IL-12 and increased TGF-β cytokine concentration in fertile women. In the case of RPL patients’ PBMCs, SC improved the production of TNF-α and IL-10. Conclusions: Lower concentration of proinflammatory cytokines in idiopathic RPL women compared to fertile women might suggest the exhaustion of the immune system. The emphasized production of IL-10 by SC partially explains the previously observed downregulation of NK cell activity in RPL patients. The immunomodulatory effect of the drug might be utilized in anti-inflammatory therapies and help achieve positive pregnancy outcomes in women with reproductive failure due to a Th1/Th2 imbalance.

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“…These examples emphasize the role of the immune system on so many other non-immune bioprocesses, which should be taken into account during assessment of possible (side-)effects of immune modulation in early life. Indeed, several chemokines and cytokines selected in our workflow, such as CXCL8, IL-10, TNF, IL1B, TGFb are multifunctional molecules initially described as having a role in endometrial functions and play a role in appropriate embryo implantation or placental functioning (46,47). Moreover, TNF and TGFb have been identified as core activators of epithelial to mesenchymal transition, which is essential for embryonic development (48,49).…”

Section: Discussionmentioning

confidence: 99%

Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

et al. 2020

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A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into prophylactic or therapeutic approaches, there is no regulatory guidance on how to assess the risk and benefit balance of such interventions. Six early life immune causal networks, each compromising a different time period in early life (the 1st, 2nd, 3rd trimester of gestations, birth, newborn, and infant period), were generated. Thereto information was extracted and structured from early life literature using the automated text mining and machine learning tool: Integrated Network and Dynamical Reasoning Assembler (INDRA). The tool identified relevant entities (e.g., genes/proteins/metabolites/processes/diseases), extracted causal relationships among these entities, and assembled them into early life-immune causal networks. These causal early life immune networks were denoised using GeneMania, enriched with data from the gene-disease association database DisGeNET and Gene Ontology resource tools (GO/GO-SLIM), inferred missing relationships and added expert knowledge to generate information-dense early life immune networks. Analysis of the six early life immune networks by PageRank, not only confirmed the central role of the "commonly used immune markers" (e.g., chemokines, interleukins, IFN, TNF, TGFB, and other immune activation regulators (e.g., CD55, FOXP3, GATA3, CD79A, C4BPA), but also identified less obvious candidates (e.g., CYP1A2, FOXK2, NELFCD, RENBP). Comparison of the different early life periods resulted in the prediction of 11 key early life genes overlapping all early life periods (TNF,

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Are the cytokines TNF alpha and IL 1Beta early predictors of embryo implantation? Cross sectional study

Cited by 21 publications

References 35 publications

Expression of IL-1β and implantation serine proteases is required for mouse blastocyst hatching

Expression of IL-1β and implantation serine proteases is required for mouse blastocyst hatching

Decreased Production of TNF-α and IL-6 Inflammatory Cytokines in Non-Pregnant Idiopathic RPL Women Immunomodulatory Effect of Sildenafil Citrate on the Cellular Response of Idiopathic RPL Women

Seeking Windows of Opportunity to Shape Lifelong Immune Health: A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

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