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PIWIL2 is overexpressed in adenomyotic lesions of women with diffuse adenomyosis

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

Adenomyosis has been studied throughout the years, however, its aetiology and physiopathology are still unknown. The aim of this study was to identify the presence of PIWI proteins in women with adenomyosis.

Methods

We included 72 participants to be part of this study and were divided into two groups based on their anatomopathological diagnosis, control (n = 36) or adenomyosis (n = 36). All samples were tested for PIWIL1, PIWIL2 and PIWIL4 proteins by immunohistochemistry. The evaluation of protein expression was performed by the digital histological score (DHSCORE) and by the pathologist’s analysis.

Results

The participants had a mean age of 44.28 ± 5.76 years and 45.81 ± 4.86 years in the control and adenomyosis groups, respectively (p ≥ 0.05). Other clinical characteristics of the participants showed no statistical difference as well. PIWIL2 is highly expressed in the adenomyosis in comparison to the control group (p = 0.0001). The PIWIL1 is downregulated in the adenomyosis (p = 0.003) and PIWIL4 showed no difference in its expression (p = 0.05).

Conclusion

PIWIL2 might be involved in cellular survival and PIWIL1 may be downregulated due to the loss of tissue’s function and response to the hostile environment of the myometrium. This is the first time that PIWI proteins are studied in the adenomyosis.

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Data availability

The datasets used and analysed during the current study are available from the corresponding author on reasonable request.

References

  1. Garavaglia E, Audrey S, Annalisa I, Stefano F, Iacopo T, Laura C et al (2015) Adenomyosis and its impact on women fertility. Iran J Reprod Med 13(6):327–336

    PubMed  PubMed Central  Google Scholar 

  2. Benagiano G, Brosens I, Habiba M (2015) Adenomyosis: a life-cycle approach. Reprod Biomed Online 30(3):220–232

    Article  CAS  Google Scholar 

  3. Bergeron C, Amant F, Ferenczy A (2006) Pathology and physiopathology of adenomyosis. Best Pract Res Clin Obstet Gynaecol 20(4):511–521

    Article  Google Scholar 

  4. Benagiano G, Habiba M, Brosens I (2012) The pathophysiology of uterine adenomyosis: an update. Fertil Steril 98(3):572–579

    Article  CAS  Google Scholar 

  5. Barrier BF, Malinowski MJ, Dick EJ, Hubbard GB, Bates GW (2004) Adenomyosis in the baboon is associated with primary infertility. Fertil Steril 82(SUPPL. 3):1091–1094

    Article  Google Scholar 

  6. Zhou S, Yi T, Liu R, Bian C, Qi X, He X et al (2012) Proteomics identification of annexin A2 as a key mediator in the metastasis and proangiogenesis of endometrial cells in human adenomyosis. Mol Cell Proteom 11(7):M112 (017988)

    Google Scholar 

  7. Carrarelli P, Yen C-F, Arcuri F, Funghi L, Tosti C, Wang T-H et al (2015) Myostatin, follistatin and activin type II receptors are highly expressed in adenomyosis. Fertil Steril 104(3):744–752.e1

    Article  CAS  Google Scholar 

  8. Qiao D, Zeeman A-M, Deng W, Looijenga LHJ, Lin H (2002) Molecular characterization of hiwi, a human member of the piwi gene family whose overexpression is correlated to seminomas. Oncogene 21(25):3988–3999

    Article  CAS  Google Scholar 

  9. Yan H, Wu Q-L, Sun C-Y, Ai L-S, Deng J, Zhang L et al (2015) piRNA-823 contributes to tumorigenesis by regulating de novo DNA methylation and angiogenesis in multiple myeloma. Leukemia 29(1):196–206 (15)

    Article  CAS  Google Scholar 

  10. Liu W-K, Jiang X-Y, Zhang Z-X (2010) Expression of PSCA, PIWIL1 and TBX2 and its correlation with HPV16 infection in formalin-fixed, paraffin-embedded cervical squamous cell carcinoma specimens. Arch Virol 155(5):657–663

    Article  CAS  Google Scholar 

  11. Fuhrich D, Lessey B, Savaris R (2013) Comparison of HSCORE assessment of endometrial beta3 integrin subunit expression with digital HSCORE using computerized image analysis (ImageJ). Anal Quant Cytopathol Histpathol 35(4):210–216

    PubMed  PubMed Central  Google Scholar 

  12. Ferreira HJ, Heyn H, Garcia del Muro X, Vidal A, Larriba S, Munoz C et al (2014) Epigenetic loss of the PIWI/piRNA machinery in human testicular tumorigenesis. Epigenetics 9(1):113–118

    Article  CAS  Google Scholar 

  13. Siddiqi S, Matushansky I (2012) Piwis and piwi-interacting RNAs in the epigenetics of cancer. J Cell Biochem 113(2):373–380

    Article  CAS  Google Scholar 

  14. Tremellen KP, Russell P (2012) The distribution of immune cells and macrophages in the endometrium of women with recurrent reproductive failure II: adenomyosis and macrophages. J Reprod Immunol 93(1):58–63

    Article  CAS  Google Scholar 

  15. Lee JH, Engel W, Nayernia K (2006) Stem cell protein Piwil2 modulates expression of murine spermatogonial stem cell expressed genes. Mol Reprod Dev 73(2):173–179

    Article  CAS  Google Scholar 

  16. Wang Q-E, Han C, Milum K, Wani AA (2011) Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment. Mutat Res 708(1–2):59–68

    Article  CAS  Google Scholar 

  17. Vannuccini S, Tosti C, Carmona F, Huang SJ, Chapron C, Guo SW et al (2017) Pathogenesis of adenomyosis: an update on molecular mechanisms. Reprod Biomed Online 35(5):592–601

    Article  CAS  Google Scholar 

  18. Kitawaki J (2006) Adenomyosis: the pathophysiology of an oestrogen-dependent disease. Best Pract Res Clin Obstet Gynaecol 20(4):493–502

    Article  Google Scholar 

  19. Goumenou A, Panayiotides I, Matalliotakis I, Vlachonikolis I, Tzardi M, Koumantakis E (2001) Bcl-2 and Bax expression in human endometriotic and adenomyotic tissues. Eur J Obstet Gynecol Reprod Biol 99(2):256–260

    Article  CAS  Google Scholar 

  20. Lee JH, Schütte D, Wulf G, Füzesi L, Radzun H-J, Schweyer S et al (2006) Stem-cell protein Piwil2 is widely expressed in tumors and inhibits apoptosis through activation of Stat3/Bcl-XL pathway. Hum Mol Genet 15(2):201–211 (15)

    Article  CAS  Google Scholar 

  21. Lim SL, Ricciardelli C, Oehler MK, Tan IMDDA, Russell D, Grutzner F (2014) Overexpression of piRNA pathway genes in epithelial ovarian cancer. PLoS ONE 9(6):e99687

    Article  Google Scholar 

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Acknowledgements

We would like to acknowledge the UPE from Centro de Pesquisa Experimental from Hospital de Clínicas de Porto Alegre that ensured the viability of the experiments by providing the laboratory’s structure and logistics for it to succeed.

Funding

The Fundação Médica do Rio Grande do Sul, Fundação Incentivo à Pesquisa e Eventos (FIPE) from Hospital de Clínicas de Porto Alegre, CNPq and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Capes) funded this study.

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Authors and Affiliations

  1. Graduate Program in Health Science: Gynaecology and Obstetrics School of Medicine, Universidade Federal Do Rio Grande Do Sul UFRGS, Rua Ramiro Barcelos, 2400, 2º andar, Porto Alegre, 90035-003, Brazil

    Marília M. C. Mattia & João Sabino Cunha-Filho

  2. Service of Surgical Pathology, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Alexandra C. P. Fernandes

  3. School of Medicine, Universidade Federal do Rio Grande do Sul UFRGS, Rua Ramiro Barcelos, 2400, Porto Alegre, 90035-003, Brazil

    Pedro da Rocha Olsen

  4. Service of Gynaecology and Obstetrics, Hospital de Clínicas de Porto Alegre, HCPA, Rua Ramiro Barcelos 2350, Porto Alegre, 90035-903, Brazil

    Vanessa K. Genro & Carlos Augusto B. de Souza

  5. Department of Gynaecology and Obstetrics, School of Medicine, Universidade Federal do Rio Grande do Sul UFRGS, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, Porto Alegre, RS, 90035-903, Brazil

    João Sabino Cunha-Filho

Authors
  1. Marília M. C. Mattia
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  2. Alexandra C. P. Fernandes
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  3. Vanessa K. Genro
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  4. Carlos Augusto B. de Souza
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  5. Pedro da Rocha Olsen
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  6. João Sabino Cunha-Filho
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Contributions

MMCM and JSLCF were responsible for the planning and execution of the project, data collection/analysis, statistical analysis, and draft of the manuscript. VKG and CABS were responsible for data collection, execution of the experiments and draft of the manuscript. PRO was responsible for ethical committee approval, planning of the project and draft of the manuscript. ACPF was responsible for participants’ selection, analysis of the immunohistochemistry results and draft of the manuscript.

Corresponding author

Correspondence to João Sabino Cunha-Filho.

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Conflict of interests

The authors declare that they have no competing interests.

Consent to participate

All participants signed an informed consent form to be part in the study.

Ethics approval

This study was approved by the Hospital de Clínicas de Porto Alegre’s (HCPA) ethics committee, and it is registered under number 16-0639 and CAAE: 63591516.0.0000.5327 at Plataforma Brasil.

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Mattia, M.M.C., Fernandes, A.C.P., Genro, V.K. et al. PIWIL2 is overexpressed in adenomyotic lesions of women with diffuse adenomyosis. Arch Gynecol Obstet 302, 925–933 (2020). https://doi.org/10.1007/s00404-020-05660-w

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  • DOI: https://doi.org/10.1007/s00404-020-05660-w

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