Increased expression of NLRP3 inflammasome components in granulosa cells and follicular fluid interleukin(IL)-1beta and IL-18 levels in fresh IVF/ICSI cycles in women with endometriosis

The inflammasomes are a family of recently described multi-protein cytoplasmic sensors that orchestrate the inflammatory response and participate in a variety of inflammatory conditions. We hypothesized that the activation of pyrin domain‑containing protein 3 (NLRP3) inflammasome by granulosa cells (hGCs) may be activated in women with endometriosis and influence oocyte maturation and IVF outcomes. We performed a cross-sectional study to investigate the NLRP3 inflammasome status in follicular fluid (FF) and in hGCs from 44 women undergoing controlled ovarian stimulation for IVF/ICSI. Study subjects were divided into two groups according to the infertility etiology: group with tubal or male factor (control, n = 22) vs. group with endometriosis (n = 22). The FF IL-1beta and IL-18 levels in the endometriosis group were significantly higher than those in the non-endometriosis group, i.e., 5010 pg/mL and 2738 pg/mL, respectively (p 0.05). In addition, the hGCs from endometriosis women demonstrated high expression of NLRP3 inflammasome at both protein and mRNA levels. Higher expression of inflammasome components within the ovary compartment may result from the exaggerated inflammatory state associated with endometriosis and thus impact the fertility of these women. Similar content being viewed by others Data availability The authors confirm that the data supporting the findings of this study are available within the article [and/or] its supplementary materials. The data that support the findings of this study are available from the corresponding authors, Bruno Fonseca or Irene Rebelo, upon reasonable request.

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The authors thank the whole staff from the CHVNG/E for their assistance. This work is financed by national funds from FCT—Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB. Funding This work was financially supported by FCT—Fundação para a Ciência e a Tecnologia, I.P., in the framework of the project PTDC/MEC-OUT/28931/2017. Author information Authors and Affiliations Contributions All authors contributed substantially to this work. The authors collectively developed the original concept of this study. BMF wrote the manuscript. IR revised it critically. Data collection and analysis were performed by BMF; BP, EF, and LC helped with the collection of follicular fluid and contributed to the data analysis and study preparation and statistical analysis by BMF. The authors contributed to critical discussion and reviewed and approved the final version of the manuscript for submission. Corresponding authors Ethics declarations Ethics approval This study was approved by the Ethics Committee of Centro Hospitalar de Vila Nova de Gaia/Espinho) and by the National Data Protection Commission (authorization number 526/2017). Informed consent was signed by the patients. Conflicts of interest The authors declare no competing interests. Additional information Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Supplementary Information Below is the link to the electronic supplementary material. Rights and permissions Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. About this article Cite this article Fonseca, B.M., Pinto, B., Costa, L. et al. Increased expression of NLRP3 inflammasome components in granulosa cells and follicular fluid interleukin(IL)-1beta and IL-18 levels in fresh IVF/ICSI cycles in women with endometriosis. J Assist Reprod Genet 40, 191–199 (2023). https://doi.org/10.1007/s10815-022-02662-2 Received: Accepted: Published: Version of record: Issue date: DOI: https://doi.org/10.1007/s10815-022-02662-2