Endometriosis is characterized by a condition where endometrial tissue grows outside the uterine cavity. The mechanisms of endometrium growth during endometriosis might be similar to the development of a tumor. The kisspeptin (KISS1) gene was initially discovered as a suppressor of metastasis. Matrix metalloproteinases (MMPs) and their inhibitors are described as factors in the early stages of endometriosis and tumor growth progression. We applied the quantitative polymerase chain reaction and the immunofluorescence method to investigate KISS1, its receptor (KISS1R), MMP-2, and MMP-9 in the eutopic and ectopic endometrium in women with and without endometriosis. We presume that the dysregulation of KISS1 and MMPs might contribute to endometriosis pathogenesis. Samples for the immunofluorescence study were collected from patients with a confirmed diagnosis of endometriosis in stages I–IV, aged 23 to 38 years old (n = 40). The cell line was derived from the endometrium of patients with extragenital endometriosis (n = 7). KISS1 and KISS1R expression are present in the ectopic endometrium of patients with extragenital endometriosis, as opposed to the control group where these proteins were not expressed. There is a decrease in KISS1 and KISS1R values at all stages of endometriosis. MMP-2 and MMP-9 genes express statistically significant increases in stages II, III, and IV of extragenital endometriosis. MMP synthesis increased in the last stages of endometriosis. We suppose that the KISS1/KISS1R system can be used in the future as a suppressive complex to reduce MMP-2 and MMP-9 expression and prevent endometrial cells from invading.

Актуальность: Механизм развития болевого синдрома при эндометриозе имеет гетерогенный характер. Установлено, что ...

Hypothesis/aims of study. Melatonin is found in almost all living organisms, the range of its effects being quite diverse. Effects of this hormone in the human body are realized via two ways, through specific receptors and non-receptor pathways. Melatonin may act through both membrane and nuclear receptors. In the present work, the expression of MTR1 and MTR2 melatonin receptors was studied in the eutopic endometrium and endometrioid heterotopies, and the level of melatonin metabolite, 6-sulfatoxymelatonin, in daily urine in patients with genital endometriosis (GE) was analyzed. Study design, materials and methods. The experimental group included 67 patients of reproductive age with a verified diagnosis of GE, and the control group consisted of 18 individuals with an ovulatory menstrual cycle without gynecological pathology. The 6-sulfatoxymelatonin level in daily urine was determined by enzyme immunoassay. The study of MTR1 and MTR2 melatonin receptor expression in the endometrium and endometrioid heterotopies was performed in 24 patients with GE and in 10 women of reproductive age who were examined for infertility who did not have gynecological pathology based on diagnostic laparoscopy. To study the expression of melatonin receptors, the endometrium and endometrial heterotopy sampling was carried out from day 18 to day 22 of the menstrual cycle. Morphological assessment included histological and immunofluorescence studies using confocal laser scanning microscopy. Results. In patients with GE, there was found a tendency to a decrease in 6-sulfatoxymelatonin excretion in daily urine compared to the control group. It was also found that the total relative expression area of melatonin receptors in the endometrium of women with GE was significantly lower compared to the endometrium of patients from the control group. Significant differences between the average brightness and optical density were not found. In addition, it was revealed that the relative expression areas of MTR1 and MTR2 melatonin receptors in the eutopic endometrium and in endometrioid heterotopies did not differ significantly. A negative correlation was stated between the relative expression area of melatonin receptors and GE prevalence. Particular attention is paid to the role of melatonin in the development of GE and to the possibilities of working out new treatment regimens with its use. Conclusion. The data obtained confirm the undoubted role of melatonin in the pathogenesis of GE, however, the development of new treatment regimens with its use requires further study.

Hypothesis/aims of study. Kisspeptin (KISS1) is encoded by KISS1 gene and its interaction with KISS1 receptor (KISS1R) suppresses metastasis and regulates release of gonadotropin-releasing hormone, which promotes secretion of estradiol and progesterone. Steroid hormone synthesis is regulated by KISS1/KISS1R and its activation can be involved in hormone dependent disorders such as endometriosis. KISS1 expression has been shown to inhibit the activity of a number of matrix metalloproteinases (MMPs). In this study, we aimed to isolate endometrial cell cultures from patients with and without endometriosis; to evaluate KISS1, KISS1R, MMP-2, and MMP-9 protein expression by immunocytochemistry; and to perform culture tests: the scratch assay and the analysis of cell migration activity. Results. It was found that the endometrial cell cultures expressed KISS1, KISS1R, MMP-2, and MMP-9 proteins, with the cell migration ability enhanced.

Kisspeptins (KPs) and their receptor (KISS1R) play an important role in many physiological processes in the body, such as sexual maturation, reproductive system functioning, placentation, insulin secretion, and vasoconstriction. The highest level of kisspeptins and their receptor is observed in the organs of hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes, both in the form of mRNA and peptide. Kisspeptins are found in various body tissues: spinal cord (Dun et al., 2003), pancreas (Song et al., 2014), esophagus (Kostakis et al., 2013), adrenal glands and secretory system organs (Wahab et al., 2015), and in malignancies (Lee and Welch, 1997). However, the localization and the role of kisspeptins and their receptor in organs during fetal development have not yet been studied. At the same time, ample published data regarding the localization of kisspeptins and their receptors in human organs and tissues are discrepant, which requires the development of a standard staining technique. The modified technique presented in this paper made it possible to identify and evaluate the expression of kisspeptins and their receptor in human fetal organs at different stages of development. Kisspeptins and their receptors were found in all organs and tissues examined by us, but the degree of reaction was different. The highest level was observed in the hypothalamus material in the 28–32-week period, and the lowest amount of the protein was detected in the uterine material at all stages. Maximum level of KISS1R was detected in the pituitary material in the 36–40-week period. A correlation between gestational age and the level of kisspeptins in the ovaries, uterus, and adrenal glands was found: a significant increase in the amount of protein was detected. A significant increase in the amount of the kisspeptin receptor in pituitary, ovary, and uterus material was shown.