Objective: The neuropeptide Kisspeptin regulates gonadotrophin-releasing hormone release from the hypothalamus and is expressed peripherally in the endometrium. It also has anti-metastatic effects in many types of cancer. Like cancer, endometriosis exhibits migration and invasiveness. Our objective was to evaluate the expression of Kisspeptin and its receptor in different endometriotic lesions.
Design: This is a case control study.
Materials and Methods: We evaluated the expression of Kisspeptin and its receptor in women with (n=35) and without (n=14) endometriosis. Eutopic endometrium was obtained from patients with (EUO-E) and without (EUO-C) endometriosis. Additionally, tissues were collected from different endometriosis phenotypes including superficial implants (SUP), deep infiltrating endometriosis (DIE), and endometriomas (OMA). Immunohistochemistry staining was performed using antibodies against Kisspeptin and Kisspeptin receptor. These antibodies were validated using Immunocytochemistry staining of HepG2 cells transfected with siRNA for KISS-1 and KISS1R genes. Signal intensity and abundance were measured using Histo-score. Data were analyzed using Student’s t and one way ANOVA tests where appropriate.
Results: In eutopic endometrium, Kisspeptin expression was significantly lower in both glandular and stromal components of EUO-E compared to EUO-C regardless of the menstrual phase (P<0.001) with no difference in receptor expression. In endometriotic implants, Kisspeptin expression was significantly lower in both glandular and stromal components of DIE (P<0.001) and OMA (P<0.01) compared to SUP. On the other hand, Kisspeptin receptor expression was only lower in glandular component of OMA (P<0.05) compared to SUP.
Conclusion: Kisspeptin and its receptor have a differential expression in patients with endometriosis with a tendency towards lower expression in the more invasive phenotypes of endometriosis. Given its anti-metastatic properties, lower Kisspeptin and Kisspeptin receptor expression may play a role in the pathogenesis of endometriosis invasiveness