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The immune milieu after local endometrial injury in women with recurrent implantation failure
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  • Published: 30 December 2025

The immune milieu after local endometrial injury in women with recurrent implantation failure

  • Yiping Fan1,2,3 na1,
  • Ryan Wai Kheong Lee2,4 na1,
  • Archita Mishra5,
  • Tse Yeun Tan1,
  • Naomi McGovern5,
  • Florent Ginhoux5 na2,
  • Yie Hou Lee2 na2 &
  • …
  • Jerry Kok Yen Chan1,2,3 na2 

Scientific Reports , Article number:  (2025) Cite this article

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We are providing an unedited version of this manuscript to give early access to its findings. Before final publication, the manuscript will undergo further editing. Please note there may be errors present which affect the content, and all legal disclaimers apply.

Subjects

  • Diseases
  • Immunology
  • Medical research

Abstract

Recurrent implantation failure (RIF) occurs in 10–15% of IVF cycles with evidence from a few randomized control trials (RCTs) that local endometrial injury (LEI) leads to higher live birth rates whose exact mechanism is currently unknown. During the implantation period, modulation in immune milieu occur in tandem with profound morphologic and functional changes in the endometrium. The landscape of immune cells in the endometrium in pre- and post-LEI in RIF is currently unknown. Thirty-seven women with RIF (age 34.6 ± 3.3 years old) underwent LEI by two sequential mid-luteal phase endometrial biopsies prior to embryo transfer. To characterize the immunological landscape alterations in LEI, we performed immunophenotypic assessment with flow cytometry to provide insights into the basal (first biopsy) and altered (second biopsy) biology of dendritic cells (DC), macrophages, natural killer (NK), T and B cells in the RIF population before and after LEI. Clinical pregnancies occurred in seventeen women (46%). Among analysed immune cells, T (34.6%) and NK cells (26.2%) predominate in the mid-luteal endometrium. A consistent increase in lymphocytes and decrease in antigen presenting cells (APCs) were observed between the two biopsies although not statistically significant. Interrogation of the immune milieu in patients who either fell pregnant or not did not show any differences once cases with endometriosis were taken out of the analyses. There were no further difference in any of the other measured immune cell subsets between the first and second endometrial biopsy. We found limited changes in the immune cell compartments after LEI. Further research with higher resolution methods may provide more information on the effects of LEI. 

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The authors confirm that the data supporting the findings are available within the article. Please contact the corresponding author for more information.

References

  1. Luke, B. et al. Cumulative birth rates with linked assisted reproductive technology cycles. N Engl. J. Med. 366, 2483–2491. https://doi.org/10.1056/NEJMoa1110238 (2012).

    Google Scholar 

  2. Karimzadeh, M. A., Ayazi Rozbahani, M. & Tabibnejad, N. Endometrial local injury improves the pregnancy rate among recurrent implantation failure patients undergoing in vitro fertilisation/intra cytoplasmic sperm injection: a randomised clinical trial. Aust N Z. J. Obstet. Gynaecol. 49, 677–680. https://doi.org/10.1111/j.1479-828X.2009.01076.x (2009).

    Google Scholar 

  3. Revel, A. Defective endometrial receptivity. Fertil. Steril. 97, 1028–1032. https://doi.org/10.1016/j.fertnstert.2012.03.039 (2012).

    Google Scholar 

  4. Segev, Y., Carp, H., Auslender, R. & Dirnfeld, M. Is there a place for adjuvant therapy in IVF? Obstet. Gynecol. Surv. 65, 260–272. https://doi.org/10.1097/OGX.0b013e3181dbc53f (2010).

    Google Scholar 

  5. Dekel, N., Gnainsky, Y., Granot, I. & Mor, G. Inflammation and implantation. Am. J. Reprod. Immunol. 63, 17–21. https://doi.org/10.1111/j.1600-0897.2009.00792.x (2010).

    Google Scholar 

  6. Tan, B. K., Vandekerckhove, P., Kennedy, R. & Keay, S. D. Investigation and current management of recurrent IVF treatment failure in the UK. BJOG 112, 773–780. https://doi.org/10.1111/j.1471-0528.2005.00523.x (2005).

    Google Scholar 

  7. Baum, M. et al. Does local injury to the endometrium before IVF cycle really affect treatment outcome? Results of a randomized placebo controlled trial. Gynecol. Endocrinol. 28, 933–936. https://doi.org/10.3109/09513590.2011.650750 (2012).

    Google Scholar 

  8. Coughlan, C. et al. Recurrent implantation failure: definition and management. Reprod. Biomed. Online. 28, 14–38. https://doi.org/10.1016/j.rbmo.2013.08.011 (2014).

    Google Scholar 

  9. Polanski, L. T. et al. What exactly do we mean by ‘recurrent implantation failure’? A systematic review and opinion. Reprod. Biomed. Online. 28, 409–423. https://doi.org/10.1016/j.rbmo.2013.12.006 (2014).

    Google Scholar 

  10. Barash, A. et al. Local injury to the endometrium doubles the incidence of successful pregnancies in patients undergoing in vitro fertilization. Fertil. Steril. 79, 1317–1322. https://doi.org/10.1016/s0015-0282(03)00345-5 (2003).

    Google Scholar 

  11. Zhou, L., Li, R., Wang, R., Huang, H. X. & Zhong, K. Local injury to the endometrium in controlled ovarian hyperstimulation cycles improves implantation rates. Fertil. Steril. 89, 1166–1176. https://doi.org/10.1016/j.fertnstert.2007.05.064 (2008).

    Google Scholar 

  12. Lensen, S., Sadler, L. & Farquhar, C. Endometrial scratching for subfertility: everyone’s doing it. Hum. Reprod. 31, 1241–1244. https://doi.org/10.1093/humrep/dew053 (2016).

    Google Scholar 

  13. Potdar, N., Gelbaya, T. & Nardo, L. G. Endometrial injury to overcome recurrent embryo implantation failure: a systematic review and meta-analysis. Reprod. Biomed. Online. 25, 561–571. https://doi.org/10.1016/j.rbmo.2012.08.005 (2012).

    Google Scholar 

  14. Nastri, C. O. et al. Endometrial injury in women undergoing assisted reproductive techniques. Cochrane Database Syst. Rev. CD009517 https://doi.org/10.1002/14651858.CD009517.pub3 (2015).

  15. Yeung, T. W. et al. The effect of endometrial injury on ongoing pregnancy rate in unselected subfertile women undergoing in vitro fertilization: a randomized controlled trial. Hum. Reprod. 29, 2474–2481. https://doi.org/10.1093/humrep/deu213 (2014).

    Google Scholar 

  16. El-Toukhy, T., Sunkara, S. & Khalaf, Y. Local endometrial injury and IVF outcome: a systematic review and meta-analysis. Reprod. Biomed. Online. 25, 345–354. https://doi.org/10.1016/j.rbmo.2012.06.012 (2012).

    Google Scholar 

  17. Sar-Shalom Nahshon, C., Sagi-Dain, L., Wiener-Megnazi, Z. & Dirnfeld, M. The impact of intentional endometrial injury on reproductive outcomes: a systematic review and meta-analysis. Hum. Reprod. Update. 25, 95–113. https://doi.org/10.1093/humupd/dmy034 (2019).

    Google Scholar 

  18. Vitagliano, A. et al. Endometrial scratch injury for women with one or more previous failed embryo transfers: a systematic review and meta-analysis of randomized controlled trials. Fertil. Steril. 110 (e682), 687–702. https://doi.org/10.1016/j.fertnstert.2018.04.040 (2018).

    Google Scholar 

  19. van Hoogenhuijze, N. E., Kasius, J. C., Broekmans, F. J. M., Bosteels, J. & Torrance, H. L. Endometrial scratching prior to IVF; does it help and for whom? A systematic review and meta-analysis. Hum. Reprod. Open. 2019 (hoy025). https://doi.org/10.1093/hropen/hoy025 (2019).

  20. Lensen, S. et al. A randomized trial of endometrial scratching before in vitro fertilization. N Engl. J. Med. 380, 325–334. https://doi.org/10.1056/NEJMoa1808737 (2019).

    Google Scholar 

  21. van Hoogenhuijze, N. E. et al. Endometrial scratching in women with one failed IVF/ICSI cycle-outcomes of a randomised controlled trial (SCRaTCH). Hum. Reprod. 36, 87–98. https://doi.org/10.1093/humrep/deaa268 (2021).

    Google Scholar 

  22. Simon, C. & Bellver, J. Scratching beneath ‘The scratching case’: systematic reviews and meta-analyses, the back door for evidence-based medicine. Hum. Reprod. 29, 1618–1621. https://doi.org/10.1093/humrep/deu126 (2014).

    Google Scholar 

  23. Fan, Y., Lee, R. W. K., Ng, X. W., Gargett, C. E. & Chan, J. K. Y. Subtle changes in perivascular endometrial mesenchymal stem cells after local endometrial injury in recurrent implantation failure. Sci. Rep. 13, 225. https://doi.org/10.1038/s41598-023-27388-8 (2023).

    Google Scholar 

  24. Cakmak, H. & Taylor, H. S. Implantation failure: molecular mechanisms and clinical treatment. Hum. Reprod. Update. 17, 242–253. https://doi.org/10.1093/humupd/dmq037 (2011).

    Google Scholar 

  25. Gnainsky, Y. et al. Biopsy-induced inflammatory conditions improve endometrial receptivity: the mechanism of action. Reproduction 149, 75–85. https://doi.org/10.1530/REP-14-0395 (2015).

    Google Scholar 

  26. Granot, I., Gnainsky, Y. & Dekel, N. Endometrial inflammation and effect on implantation improvement and pregnancy outcome. Reproduction 144, 661–668. https://doi.org/10.1530/REP-12-0217 (2012).

    Google Scholar 

  27. Arck, P. C. & Hecher, K. Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat. Med. 19, 548–556. https://doi.org/10.1038/nm.3160 (2013).

    Google Scholar 

  28. Saito, S. et al. Distribution of Th1, Th2, and Th0 and the Th1/Th2 cell ratios in human peripheral and endometrial T cells. Am. J. Reprod. Immunol. 42, 240–245. https://doi.org/10.1111/j.1600-0897.1999.tb00097.x (1999).

    Google Scholar 

  29. Brosens, I., Pijnenborg, R., Vercruysse, L. & Romero, R. The great obstetrical syndromes are associated with disorders of deep placentation. Am. J. Obstet. Gynecol. 204, 193–201. https://doi.org/10.1016/j.ajog.2010.08.009 (2011).

    Google Scholar 

  30. Gnainsky, Y., Dekel, N. & Granot, I. Implantation: mutual activity of sex steroid hormones and the immune system guarantee the maternal-embryo interaction. Semin Reprod. Med. 32, 337–345. https://doi.org/10.1055/s-0034-1376353 (2014).

    Google Scholar 

  31. Wegmann, T. G., Lin, H., Guilbert, L. & Mosmann, T. R. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol. Today. 14, 353–356. https://doi.org/10.1016/0167-5699(93)90235-D (1993).

    Google Scholar 

  32. Haniffa, M. et al. Human tissues contain CD141hi cross-presenting dendritic cells with functional homology to mouse CD103 + nonlymphoid dendritic cells. Immunity 37, 60–73. https://doi.org/10.1016/j.immuni.2012.04.012 (2012).

    Google Scholar 

  33. Vitagliano, A. et al. Endometrial scratching can be offered outside clinical research setting: let Us show you why. Hum. Reprod. 36, 1447–1449. https://doi.org/10.1093/humrep/deab060 (2021).

    Google Scholar 

  34. Dickinson, R. E. et al. The evolution of cellular deficiency in GATA2 mutation. Blood 123, 863–874. https://doi.org/10.1182/blood-2013-07-517151 (2014).

    Google Scholar 

  35. van Hoogenhuijze, N. E. et al. Endometrial scratching in women undergoing IVF/ICSI: an individual participant data meta-analysis. Hum. Reprod. Update. 29, 721–740. https://doi.org/10.1093/humupd/dmad014 (2023).

    Google Scholar 

  36. Kammerer, U., von Wolff, M. & Markert, U. R. Immunology of human endometrium. Immunobiology 209, 569–574. https://doi.org/10.1016/j.imbio.2004.04.009 (2004).

    Google Scholar 

  37. Flynn, L. et al. Menstrual cycle dependent fluctuations in NK and T-lymphocyte subsets from non-pregnant human endometrium. Am. J. Reprod. Immunol. 43 (4), 209–217. https://doi.org/10.1111/j.8755-8920.2000.430405.x (2000).

    Google Scholar 

  38. Salamonsen, L. A. & Lathbury, L. J. Endometrial leukocytes and menstruation. Hum. Reprod. Update. 6, 16–27. https://doi.org/10.1093/humupd/6.1.16 (2000).

    Google Scholar 

  39. Schlitzer, A., McGovern, N. & Ginhoux, F. Dendritic cells and monocyte-derived cells: two complementary and integrated functional systems. Semin Cell. Dev. Biol. 41, 9–22. https://doi.org/10.1016/j.semcdb.2015.03.011 (2015).

    Google Scholar 

  40. Brighton, P. J. et al. Clearance of senescent decidual cells by uterine natural killer cells in cycling human endometrium. Elife 6 https://doi.org/10.7554/eLife.31274 (2017).

  41. Marron, K., Walsh, D. & Harrity, C. Detailed endometrial immune assessment of both normal and adverse reproductive outcome populations. J. Assist. Reprod. Genet. 36, 199–210. https://doi.org/10.1007/s10815-018-1300-8 (2019).

    Google Scholar 

  42. Fan, X. et al. Immune profiling and RNA-seq uncover the cause of partial unexplained recurrent implantation failure. Int. Immunopharmacol. 121, 110513. https://doi.org/10.1016/j.intimp.2023.110513 (2023).

    Google Scholar 

  43. Gnainsky, Y. et al. Local injury of the endometrium induces an inflammatory response that promotes successful implantation. Fertil. Steril. 94, 2030–2036. https://doi.org/10.1016/j.fertnstert.2010.02.022 (2010).

    Google Scholar 

  44. Givan, A. L. et al. Flow cytometric analysis of leukocytes in the human female reproductive tract: comparison of fallopian tube, uterus, cervix, and vagina. Am. J. Reprod. Immunol. 38, 350–359. https://doi.org/10.1111/j.1600-0897.1997.tb00311.x (1997).

    Google Scholar 

  45. Raphael, I., Nalawade, S., Eagar, T. N. & Forsthuber, T. G. T cell subsets and their signature cytokines in autoimmune and inflammatory diseases. Cytokine 74, 5–17. https://doi.org/10.1016/j.cyto.2014.09.011 (2015).

    Google Scholar 

  46. Ganeva, R. et al. Endometrial immune cell ratios and implantation success in patients with recurrent implantation failure. J. Reprod. Immunol. 156, 103816. https://doi.org/10.1016/j.jri.2023.103816 (2023).

    Google Scholar 

  47. Lee, J. Y., Lee, M. & Lee, S. K. Role of endometrial immune cells in implantation. Clin. Exp. Reprod. Med. 38, 119–125. https://doi.org/10.5653/cerm.2011.38.3.119 (2011).

    Google Scholar 

  48. Carlino, C. et al. Recruitment of Circulating NK cells through decidual tissues: a possible mechanism controlling NK cell accumulation in the uterus during early pregnancy. Blood 111, 3108–3115. https://doi.org/10.1182/blood-2007-08-105965 (2008).

    Google Scholar 

  49. Moffett-King, A. Natural killer cells and pregnancy. Nat. Rev. Immunol. 2, 656–663. https://doi.org/10.1038/nri886 (2002).

    Google Scholar 

  50. Dosiou, C. & Giudice, L. C. Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and Immunologic perspectives. Endocr. Rev. 26, 44–62. https://doi.org/10.1210/er.2003-0021 (2005).

    Google Scholar 

  51. Okada, H., Tsuzuki, T. & Murata, H. Decidualization of the human endometrium. Reprod. Med. Biol. 17, 220–227. https://doi.org/10.1002/rmb2.12088 (2018).

    Google Scholar 

  52. Lee, S. K., Kim, C. J., Kim, D. J. & Kang, J. H. Immune cells in the female reproductive tract. Immune Netw. 15, 16–26. https://doi.org/10.4110/in.2015.15.1.16 (2015).

    Google Scholar 

  53. Kofod, L., Lindhard, A. & Hviid, T. V. F. Implications of uterine NK cells and regulatory T cells in the endometrium of infertile women. Hum. Immunol. 79, 693–701. https://doi.org/10.1016/j.humimm.2018.07.003 (2018).

    Google Scholar 

  54. Giuliani, E., Parkin, K. L., Lessey, B. A., Young, S. L. & Fazleabas, A. T. Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis. Am. J. Reprod. Immunol. 72, 262–269. https://doi.org/10.1111/aji.12259 (2014).

    Google Scholar 

  55. Matteo, M. G. et al. Normal percentage of CD56bright natural killer cells in young patients with a history of repeated unexplained implantation failure after in vitro fertilization cycles. Fertil. Steril. 88, 990–993. https://doi.org/10.1016/j.fertnstert.2007.01.028 (2007).

    Google Scholar 

  56. Koopman, L. A. et al. Human decidual natural killer cells are a unique NK cell subset with Immunomodulatory potential. J. Exp. Med. 198, 1201–1212. https://doi.org/10.1084/jem.20030305 (2003).

    Google Scholar 

  57. Caligiuri, M. A. Human natural killer cells. Blood 112, 461–469. https://doi.org/10.1182/blood-2007-09-077438 (2008).

    Google Scholar 

  58. Shen, M. et al. B cell subset analysis and gene expression characterization in Mid-Luteal endometrium. Front. Cell. Dev. Biol. 9, 709280. https://doi.org/10.3389/fcell.2021.709280 (2021).

    Google Scholar 

  59. Shen, M. et al. The role of endometrial B cells in normal endometrium and benign female reproductive pathologies: a systematic review. Hum. Reprod. Open. 2022, hoab043. https://doi.org/10.1093/hropen/hoab043 (2022).

    Google Scholar 

  60. Kambayashi, T. & Laufer, T. M. Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? Nat. Rev. Immunol. 14, 719–730. https://doi.org/10.1038/nri3754 (2014).

    Google Scholar 

  61. Haniffa, M., Collin, M. & Ginhoux, F. Ontogeny and functional specialization of dendritic cells in human and mouse. Adv. Immunol. 120, 1–49. https://doi.org/10.1016/B978-0-12-417028-5.00001-6 (2013).

    Google Scholar 

  62. Villadangos, J. A. & Schnorrer, P. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat. Rev. Immunol. 7, 543–555. https://doi.org/10.1038/nri2103 (2007).

    Google Scholar 

  63. Boltjes, A. & van Wijk, F. Human dendritic cell functional specialization in steady-state and inflammation. Front. Immunol. 5, 131. https://doi.org/10.3389/fimmu.2014.00131 (2014).

    Google Scholar 

  64. Jongbloed, S. L. et al. Human CD141+ (BDCA-3) + dendritic cells (DCs) represent a unique myeloid DC subset that cross-presents necrotic cell antigens. J. Exp. Med. 207, 1247–1260. https://doi.org/10.1084/jem.20092140 (2010).

    Google Scholar 

  65. Rodriguez-Garcia, M., Fortier, J. M., Barr, F. D. & Wira, C. R. Isolation of dendritic cells from the human female reproductive tract for phenotypical and functional studies. J. Vis. Exp. https://doi.org/10.3791/57100 (2018).

    Google Scholar 

  66. Ticconi, C., Pietropolli, A., Di Simone, N., Piccione, E. & Fazleabas, A. Endometrial immune dysfunction in recurrent pregnancy loss. Int. J. Mol. Sci. 20 https://doi.org/10.3390/ijms20215332 (2019).

  67. Wilczyński, J. R. Immunological analogy between allograft rejection, recurrent abortion and pre-eclampsia - the same basic mechanism? Hum. Immunol. 67, 492–511. https://doi.org/10.1016/j.humimm.2006.04.007 (2006).

    Google Scholar 

  68. Vallve-Juanico, J., Houshdaran, S. & Giudice, L. C. The endometrial immune environment of women with endometriosis. Hum. Reprod. Update. 25, 564–591. https://doi.org/10.1093/humupd/dmz018 (2019).

    Google Scholar 

  69. Patel, B. G. et al. Pathogenesis of endometriosis: interaction between endocrine and inflammatory pathways. Best Pract. Res. Clin. Obstet. Gynaecol. 50, 50–60. https://doi.org/10.1016/j.bpobgyn.2018.01.006 (2018).

    Google Scholar 

  70. Agic, A. et al. Is endometriosis associated with systemic subclinical inflammation? Gynecol. Obstet. Invest. 62, 139–147. https://doi.org/10.1159/000093121 (2006).

    Google Scholar 

  71. Hoeffel, G. et al. Adult Langerhans cells derive predominantly from embryonic fetal liver monocytes with a minor contribution of yolk sac-derived macrophages. J. Exp. Med. 209, 1167–1181. https://doi.org/10.1084/jem.20120340 (2012).

    Google Scholar 

  72. McGovern, N. et al. Human dermal CD14(+) cells are a transient population of monocyte-derived macrophages. Immunity 41, 465–477. https://doi.org/10.1016/j.immuni.2014.08.006 (2014).

    Google Scholar 

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Acknowledgements

The authors wish to thank Dr Sadhana Nadarajah, Dr Tan Heng Hao, Miss Ng Xiang Wen from KK Women’s and Children’s Hospital for clinical administrative support, Mr Gurmit Singh from Singapore Immunology Network (SIgN) for tissue sample processing and flow cytometry analysis.

Funding

This study was supported by the KK Women’s and Children’s Hospital Health Endowment Fund (KKHHEF/2013/07), Academic Medicine Start up Grant (AM/SU101/2024), Improving Fertility Outcomes in Women Programme Fund sponsored by Melilea International Group of Companies, and National Medical Research council (NMRC) seed fund (0004/2017). JKYC is supported by National Medical Research Council (CIRG/1484/2018, NMRC CSA (SI)/008/2016, CIRG21jun-0045 and STaR22jul-0004).

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Author notes

  1. Yiping Fan and Ryan Wai Kheong Lee are Joint first authors.

  2. Florent Ginhoux, Yie Hou Lee and Jerry Kok Yen Chan are Joint last authors.

Authors and Affiliations

  1. Department of Reproductive Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Yiping Fan, Tse Yeun Tan & Jerry Kok Yen Chan

  2. Obstetrics and Gynaecology Academic Clinical Programme, Duke-NUS Medical School, Singapore, Singapore

    Yiping Fan, Ryan Wai Kheong Lee, Yie Hou Lee & Jerry Kok Yen Chan

  3. Department of Obstetrics and Gynaecology, National University of Singapore, Singapore, Singapore

    Yiping Fan & Jerry Kok Yen Chan

  4. Department of Maternal-Fetal Medicine, KK Women’s and Children’s Hospital, Singapore, Singapore

    Ryan Wai Kheong Lee

  5. Singapore Immunology Network (SigN), A-STAR, 8 A Biomedical Grove, Singapore, Singapore

    Archita Mishra, Naomi McGovern & Florent Ginhoux

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Contributions

FG, YHL and JKYC study conceptualization. AM and NM designed and performed the flow experiments. RWKL, YF, YHL analysed the data and drafted the paper. RWKL, TYT, JKYC obtained funding, consented patients and collected data. All authors read, reviewed and approved the final version of the article.

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Fan, Y., Lee, R.W.K., Mishra, A. et al. The immune milieu after local endometrial injury in women with recurrent implantation failure. Sci Rep (2025). https://doi.org/10.1038/s41598-025-34198-7

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  • Received: 30 August 2025

  • Accepted: 26 December 2025

  • Published: 30 December 2025

  • DOI: https://doi.org/10.1038/s41598-025-34198-7

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