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Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis

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Abstract

Endometriosis is characterized by the presence of ectopic endometrial tissues. Mechanisms of tissue dissemination in endometriosis may be similar to those involved in tumor metastasis. We hypothesize that dysregulation of kisspeptin (KISS1), a metastasis suppressor in endometrial carcinoma, may contribute to the pathogenesis of endometriosis. In this study, we characterized the immunoreactivity of kisspeptin and its receptor, KISS1R, in eutopic and ectopic endometrial tissue of women with and without endometriosis, in proliferative and secretory menstrual cycle phases. Immunohistochemistry was performed using KISS1 and KISS1R antibodies on samples from women with (n = 35) and without (n = 14) endometriosis. Samples from women with endometriosis included eutopic endometrium (n = 20) samples, superficial endometriotic implants (SUP, n = 10) deep infiltrating endometriotic implants (DIE, n = 15), and ovarian endometriomas (OMA, n = 15). Immunoreactivity was quantified using histoscores. KISS1 and KISS1R immunoreactivity was significantly lower in eutopic endometrial stroma of women with versus without endometriosis, regardless of the menstrual cycle phase (P = 0.001 and P = 0.015 respectively). In endometriotic implants, KISS1 levels were significantly lower in both glandular and stromal components of DIE (P < 0.01) and OMA (P < 0.01) compared to SUP. KISS1R immunoreactivity was lower in the glandular component of OMA (P = 0.035) compared to SUP. KISS1 and KISS1R levels are lower in eutopic endometrial stroma from women with versus without endometriosis, consistent with a role for decreased KISS1 expression in the pathogenesis of endometriosis. As deeply invasive lesions showed lower KISS1 levels than superficial lesions, downregulation of KISS1 levels may contribute to implant invasiveness.

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Acknowledgments

The authors thank Professor Eman M. S. Muhammad from the pathology department at Sohag University in Egypt and Dr. Julia Naso from the pathology department at The University of British Columbia in Canada for their help with the study.

Funding

This project was internally funded by the Department of Obstetrics and Gynecology, University of British Columbia, Vancouver, BC, Canada, and by the joint supervision scholarships program, Egyptian Ministry of higher education, Cairo, Egypt.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, Faculty of Medicine, Sohag University, Sohag, Egypt

    Amr O. Abdelkareem, Abdou S. Ait-Allah, Salah M. Rasheed & Yasser A. Helmy

  2. Department of Obstetrics and Gynaecology, Faculty of Medicine, University of British Columbia, Vancouver, Canada

    Amr O. Abdelkareem, Fahad T. Alotaibi, Ghadeer M. AlKusayer, Catherine Allaire, Bo Peng, Paul J. Yong & Mohamed A. Bedaiwy

  3. Department of Clinical Sciences, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Kingdom of Saudi Arabia

    Ghadeer M. AlKusayer

  4. BC Women’s Hospital, Room D415A, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada

    Mohamed A. Bedaiwy

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  1. Amr O. Abdelkareem
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This work was completed at the British Columbia Women’s Hospital, Vancouver, Canada and the BC Children’s Hospital Research Institute, Vancouver, Canada.

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Abdelkareem, A.O., Alotaibi, F.T., AlKusayer, G.M. et al. Immunoreactivity of Kisspeptin and Kisspeptin Receptor in Eutopic and Ectopic Endometrial Tissue of Women With and Without Endometriosis. Reprod. Sci. 27, 1731–1741 (2020). https://doi.org/10.1007/s43032-020-00167-w

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