The role of metastin in pathogenesis of genital endometriosis

Materials and methods. 28 patients with GE of I-II degrees of prevalence (R-AFS) were included in the study. Control group consisted of 11 healthy women. All the patients underwent laparoscopy and hysteroscopy with histological examination of ovarian tissue, peritoneum and endometrium; patients with GE also were performed histological examination of endometrioid of heterotopies. Definition of levels of kisspeptin, FSH, LH, prolactin, AMH, estradiol, estrone, androgens (free testosterone, dehydroepiandrosterone – DHEA) in peripheral blood in healthy women and in patients with GE were conducted by ELISA on the 2nd and 8th days of menstrual cycle. Immunohistochemical method was used to evaluate expression of metastine (kisspeptin) and its receptor in ovarian tissue, peritoneum, in endometrioid heterotopies and in endometrium.

Results. Hormonal survey has revealed that the level of kisspeptin in peripheral blood was reliably higher compared to its level in the control group. Immunohistochemical study found that in patients with GE area of expression of KISS and KISS1R receptor in endometrium was reliably lower when compared with these values in the control group. In the foci of endometrioid heterotopies, which were located on the pelvic peritoneum, it was observed a reliable increase in protein КІЅЅ1 expression and receptor KISS1R compared to fragments of intact peritoneum. The area of expression of receptor KISS1R in endometrioid heterotopies was reliably higher than the area of its expression in endometrium of patients with GE and in endometrium of women of the control group. Direct correlation between the area of protein expression (KISS) in endometrium with level kisspeptin on the 8th day of menstrual cycle in peripheral blood (rs = 0,90) has been revealed. It has been determined that the level of kisspeptin on the 2nd day of menstrual cycle in peripheral blood correlates with the area of expression of receptor KISS1R in peritoneum (rs = 0,57). A direct correlation between the area of expression of receptor KISS1R in peritoneum with the level of kisspeptin on the 8th day of menstrual cycle in serum has been found (rs = 0,90).

Conclusion. The obtained data show a definite role of kisspeptin in pathogenesis of genital endometriosis. It can be assumed that the increase in the level of metastine (kisspeptin) in peripheral blood and increased expression of KISS1 in endometrioid heterotopies and especially its receptor KISS1R are compensatory-adaptive response aimed at deterrence of further spread of endometriosis. The obtained results justify the need to continue research in this direction for a deeper understanding of pathogenesis of the disease and possible use of kisspeptin as biomarker for non-invasive diagnostics as well as potential targeted therapy of GE.