Skirtingi ir bendri endometriozės ir negimdinio nėštumo molekuliniai mechanizmai

Molecular Mechanisms of Endometriosis and Ectopic Pregnancy: Individual and Overlapping Pathways Lillemo, Linnea Gabriella | Recenzentas / Reviewer | Darbo tikslas buvo sistemingai nustatyti molekulinius ir ląstelinius mechanizmus, atskirai lemiančius endometriozę ir negimdinį nėštumą, bei identifikuoti bendrus biologinius kelius. Endometriozės atveju nustatyti šie mechanizmai: imuninės sistemos disreguliacija, padidėjęs citokinų kiekis, hiperestrogenizmas ir atsparumas progesteronui, Wnt/β-katenino signalinis kelias, geležies perteklius ir ferozė (ferroptozė), endokanabinoidinė sistema bei nekoduojančios RNR. Negimdiniam nėštumui buvo būdingas sumažėjęs NK ląstelių aktyvumas, padidėjęs citokinų kiekis, estrogeno ir progesterono receptorių disreguliacija, kiaušintakių funkcijos sutrikimai bei Chlamydia trachomatis infekcija. Kaip persidengiantys mechanizmai buvo nustatyti M2 makrofagų poliarizacija, Wnt/β-katenino signalinio kelio aktyvacija ir let-7 disreguliacija. Research title: Molecular Mechanisms of Endometriosis and Ectopic Pregnancy: Individual and Overlapping Pathways Aim and objectives: The aim of the thesis was to systematically identify the molecular and cellular mechanisms underlying endometriosis and ectopic pregnancy separately, and to identify the shared biological pathways. The objectives were to identify and analyse the main molecular mechanisms involved in the pathophysiology of both endometriosis and ectopic pregnancy and how they contribute to the development of both conditions, to compare the overlapping molecular mechanisms, and to assess potential therapeutic targets for both conditions. Methodology: A systematic review was undertaken following the PRISMA guidelines. Studies which investigated any molecular and/or cellular mechanism of either endometriosis or ectopic pregnancy were eligible. The search was conducted from November 1st 2025 until the 31st of March 2026 using electronic databases PubMed, Nature, and ScienceDirect. Study participants: Women with endometriosis or ectopic pregnancy. Research results, conclusions and recommendations: This systematic review identified 105 studies on endometriosis and 66 on ectopic pregnancy. In endometriosis, immune dysregulation exhibited increased mast cells, altered Treg distribution and M2 polarization of macrophages, as well as elevated cytokines. Hyperestrogenism and progesterone resistance were identified along with involvement of the Wnt/β-catenin pathway, iron overload and ferroptosis. The endocannabinoid system and several non-coding RNAs were also implicated. Ectopic pregnancy featured reduced NK cell activity, elevated cytokines, and dysregulated estrogen and progesterone receptors. Tubal dysfunction and Chlamydia trachomatis also contributed on a molecular level. Overlapping mechanisms were identified as M2 macrophage polarization, Wnt/β-catenin pathway activation, and let-7 dysregulation. Potential therapeutic targets for endometriosis were mast cells, macrophage polarization, the NLRP3 inflammasome, IL-1β, TGF-β, the Wnt/β-catenin pathway and ferroptosis. For ectopic pregnancy, possible targets include macrophage polarization, LIF, EphA2, VEGF and the Wnt/β-catenin pathway. It is recommended by the author to further research and validate potential therapeutic candidates, develop biomarker panels using the knowledge on specific molecular expression patterns, and conduct phase 2 clinical trials to repurpose already existing medications for the treatment of endometriosis.