Local synthesis of neuropeptides in female reproductive tissues and synergism of kisspeptin and oxytocin in endometriosis development

BACKGROUND: Previous studies leave no doubt as to the involvement of kisspeptin and oxytocin in the pathogenesis of endometriosis. Oxytocin and kisspeptin levels in the peripheral blood of patients with endometriosis were shown to be higher than in the comparison group, and these proteins were detected in the eutopic endometrium of patients with endometriosis. Local synthesis of these neuropeptides in female reproductive tissues may presumably play a significant role in the development of the disease. AIM: The aim of this study was to evaluate KISS1 and OXT gene expressions in the peritoneum, ectopic and eutopic endometrium of patients with endometriosis and women in the comparison group.

This single-center cohort study analyzed a collection of tissues (eutopic endometrium, peritoneum, peritoneal endometrioid heterotopias, endometrioid ovarian cysts, endometrioid infiltrates) obtained from patients with endometriosis and a comparison group of women undergoing examination and treatment at the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott. Total RNA was isolated from the samples, and the relative expression levels of the KISS1 and OXT genes were determined using real-time reverse transcription-polymerase chain reaction.

The main group included 106 patients, and the comparison group included 104 individuals. The following gene expression patterns were found in patients with endometriosis. KISS1 gene overexpression was detected in the peritoneum and, to a lesser extent, in the eutopic endometrium. OXT gene expression was elevated in the eutopic endometrium and, in some cases, in the peritoneum. OXT gene overexpression was observed in endometriotic infiltrates, but not in peritoneal lesions or endometriotic cysts.

In endometriosis, the KISS1 and OXT genes are expressed at high levels in peripheral tissues (endometrium, peritoneum). These expression patterns are tissue-specific and are observed not only in endometriotic lesions (endometrioid infiltrates) but also in morphologically normal tissues. Possible mechanisms by which kisspeptin and oxytocin influence the development of the symptom complex of endometriosis are discussed.

Full Text About the authors Natalia Yu. Shved The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Author for correspondence. Email: [email protected] ORCID iD: 0000-0001-6354-9226 SPIN-code: 8276-1720 Cand. Sci. (Biology) Russian Federation, Saint PetersburgArsenii S. Molotkov The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0003-3433-3092 MD, Cand. Sci. (Medicine) Russian Federation, Saint PetersburgMaria A. Shalina The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-5921-3217 SPIN-code: 6673-2660 MD, Cand. Sci. (Medicine) Russian Federation, Saint PetersburgMaria I. Yarmolinskaya The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-6551-4147 SPIN-code: 3686-3605 MD, Dr. Sci. (Medicine), Professor, Professor of the Russian Academy of Sciences, Honored Scientist of the Russian Federation Russian Federation, Saint PetersburgOlga V. Malysheva The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott Email: [email protected] ORCID iD: 0000-0002-8626-5071 SPIN-code: 1740-2694 Cand. Sci. (Biology) Russian Federation, Saint PetersburgReferences - Adamyan LV, Andreeva EN. Endometriosis and its global impact on a woman’s body. Russian Journal of Human Reproduction. 2022;28(1):54–64. doi: 10.17116/repro20222801154 EDN: ELOTDZ - Alekseeva MN, Khashchenko EP, Uvarova EV. The main pathogenetic links of endometriosis: hyperestrogenism, immunotolerance, proliferation and dissemination of endometrioid cells. Pediatric and Adolescent Reproductive Health. 2023;19(3):44–61. doi: 10.33029/1816-2134-2022-19-3-44-61 EDN: WOMGJZ - Zondervan KT, Becker CM, Missmer SA. Endometriosis. 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