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Lupus progression deteriorates oogenesis quality in MRL/lpr mice

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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of the immune response against self antigens. Numerous reproductive complications, including reduced birth rate and complications for the mother and the fetus during pregnancy, have been observed in women with SLE. In the present study, we aimed to investigate the effect of SLE development on oocyte meiosis in lupus-prone mice. Lupus-prone MRL/lpr mice were used for the experiments: disease-free (4 weeks of age) and sick (20 weeks of age, virgin and postpartum). The immune response was monitored by flow cytometry, ELISpot, ELISA, and histology. Oocytes were analyzed by fluorescence microscopy based on chromatin, tubulin, and actin structures. The lupus-prone MRL/lpr mice developed age-dependent symptoms of SLE with increased levels of various autoantibodies, proteinuria, and renal infiltrates and a tendency for the immune response to worsen with changes in cell populations and the cytokine profile. The number and quality of oocytes were also affected, and the successful pregnancy rate of MRL/lpr mice was limited to only 60%. Isolated oocytes showed severe structural changes in all studied groups. Systemic alterations in immune homeostasis in SLE affect the quality of developing oocytes, which is evident from a young age. The data obtained is in line with the trend of reduced fertility in lupus-prone MRL/lpr mice. The phenomenon can be explained by changes in the microenvironment of the relevant organs and close connection between ovulation and inflammatory processes.

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Data Availability

Data is available from the corresponding author upon reasonable request.

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Funding

This study was supported by the Medical University of Sofia (grants ref. 25/2016, 65/2018); the European Fund for regional development through Operational Program Science and Education for Smart Growth 2014—2020, Grant BG05M2OP001-1.002–0001-C04 “Fundamental Translational and Clinical Investigations on Infections and Immunity”); and National Science Fund, Bulgaria, grant number [КP-06-H53/8/2021].

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Authors and Affiliations

  1. Department of Biology, Medical University of Sofia, 2, Zdrave Str., 1431, Sofia, Bulgaria

    Stefka Delimitreva, Irina Chakarova, Valentina Hadzhinesheva, Ralitsa Zhivkova, Maya Markova, Venera Nikolova, Anton Kolarov & Nikola Mladenov

  2. Department of Immunology, Stefan Angelov Institute of Microbiology, Bulgarian Academy of Sciences, Acad. G. Bonchev Street, Block 26, 1113, Sofia, Bulgaria

    Gabriela Boneva, Silviya Bradyanova, Nikolina Mihaylova & Andrey Tchorbanov

  3. R&D Laboratory, Diagnosticum Zrt, Budapest, Hungary

    József Prechl

  4. National Institute of Immunology, 1517, Sofia, Bulgaria

    Andrey Tchorbanov

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  1. Stefka Delimitreva
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  2. Gabriela Boneva
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  3. Irina Chakarova
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  7. Venera Nikolova
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Contributions

G. B.: investigation, methodology, formal analysis, writing – original draft; I. C., V. H., R. Z., M. M., V. N., A. K., N. Mladenov: investigation, methodology, visualization; S. B.: investigation, methodology, formal analysis; N. Mihaylova: methodology, formal analysis; S. D., A. T,: conceptualization, methodology, formal analysis, writing – review and editing, supervision.

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Correspondence to Stefka Delimitreva or Andrey Tchorbanov.

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Delimitreva, S., Boneva, G., Chakarova, I. et al. Lupus progression deteriorates oogenesis quality in MRL/lpr mice. Immunol Res (2024). https://doi.org/10.1007/s12026-024-09489-2

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