P–238 Impaired oocyte fertilization is associated with a proinflammatory M1 phenotype of macrophages and the activation of the NLRC4 inflammasome
| العنوان: | P–238 Impaired oocyte fertilization is associated with a proinflammatory M1 phenotype of macrophages and the activation of the NLRC4 inflammasome |
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| المؤلفون: | A Bielfeld, Benjamin Rösing, Pardes Habib, Josef Neulen |
| المصدر: | Human Reproduction. 36 |
| بيانات النشر: | Oxford University Press (OUP), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_treatment, Rehabilitation, Caspase 1, Obstetrics and Gynecology, Inflammasome, Inflammation, Biology, Oocyte, Phenotype, Proinflammatory cytokine, Cell biology, Cytokine, medicine.anatomical_structure, Reproductive Medicine, NLRC4, medicine, medicine.symptom, medicine.drug |
| الوصف: | Study question Are inflammatory signatures in the blood of clinically asymptomatic patients predictive for oocyte fertilization success in ART treatment? Summary answer The proinflammatory M1 phenotype of macrophages combined with increasing numbers of cytotoxic T-cells and an upregulated inflammasome NLRC4 is associated with impaired oocyte fertilization. What is known already Oocyte fertilization is an indispensable step towards embryogenesis and reproductive success. Patients with acute or chronic inflammation are at risk of reduced fertilization rates and failure of assisted reproductive technology (ART) treatment. Inflammasomes are intracellular multiprotein complexes that mediate inflammatory tissue remodeling. They can be activated by endogenous and exogenous stimuli and result in maturation of the cytokines IL–1βand IL–18. Appropriate inflammasome activation serves for pathogen defense and tissue damage repair, while aberrant activation of inflammasomes can enhance uncontrolled tissue damage. Study design, size, duration This a prospective study including 39 patients stratified by fertilization rate (cut off 66%) of mature M II oocytes after ICSI procedure, compares 20 patients with high (mean 84,8%, range 67 –100%) versus 19 patients with low (mean 29.4%, range 0–65%) rates. Participants/materials, setting, methods We performed FACS analysis of immune cell composition (leukocytes, neutrophils, monocytes, macrophage types M1 and M2, cytotoxic T-cells, T-helper cells) and utilized RT-qPCR analysis of three inflammasomes (AIM 2, NLRP3 and NLRC4) and their down-streaming proteins caspase 1 and IL–1ß. We focused on an initial and a late state during controlled ovarian stimulation (COS) procedure. Main results and the role of chance This study reports a cellular and molecular inflammatory signature associated with reduced oocyte fertilization rates after ICSI treatment in clinically asymptomatic patients. On a cellular level proinflammatory M1 macrophages were significantly elevated in the low fertilization group (p In line with this pattern, there was a significant upregulation of Caspase 1 with a consecutive increase in IL–1ß activity in women with low fertilization rates (p No significant association was shown for the other tested immune cells (leukocytes, neutrophils, monocytes, T-helper cells) and inflammasomes (NLRC3, AIM2). Limitations, reasons for caution The preliminary results in this small study indicate an activation of the inflammasome NLRC4. This, however, has to be assessed on the protein level in a larger group of patients. Wider implications of the findings: Systemic macrophage augmentation of M1 phenotype and cytotoxic T cell presence in combination with upregulated inflammasome NLRC4 are associated with impaired oocyte fertilization. The predictive information of the identified immunologic signature could indicate targeted treatment to down regulate systemic inflammation and the use of oocyte activators in the ART laboratory. Trial registration number none |
| تدمد: | 1460-2350 0268-1161 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::0ef527f625ce8e55a9e137933677bc83 https://doi.org/10.1093/humrep/deab130.237 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........0ef527f625ce8e55a9e137933677bc83 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14602350 02681161 |
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