Research Project: Vajinal Mikrobiyota Disbiyozunun Intestinal ve Genital Inflamasyonun Aktivasyonu ve Gebelik Süreci ile Iliskisinin in vivo Fare Modelinde Incelenmesi
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Contributors
Funders
ID
TB.00756
Authors
Kuyucu, Gülin Özcan
PhD Student
Publications
Dysbiosis in pregnant mice induced by transfer of human vaginal microbiota followed by reversal of pathological changes in the uterus and placenta via progesterone treatment
(BMC, 2024) Albayrak, Özgür; Alnajjar, Iman; Can, Füsun; Çelik, Ebru; Coşkun, Nilhan; Eren, Özgür Can; Gürsoy, Attila; Kuyucu, Gülin Özcan; Keskin, Özlem; Paerhati, Erxiati; Şahin, Deniz; Talay, Zeynep Gülce; KUISCID (Koç University İşbank Center for Infectious Diseases); Department of Computer Engineering; Department of Chemical and Biological Engineering; Graduate School of Health Sciences; School of Medicine; KUTTAM (Koç University Research Center for Translational Medicine); KUH (Koç University Hospital); Yes; College of Engineering; Research Center; GRADUATE SCHOOL OF HEALTH SCIENCES; KUH (KOÇ UNIVERSITY HOSPITAL); SCHOOL OF MEDICINE
Objective The vaginal microbiota dysbiosis induces inflammation in the uterus that triggers tissue damage and is associated with preterm birth. Progesterone is used to prevent labor in pregnant women at risk of preterm birth. However, the mechanism of action of progesterone still needs to be clarified. We aimed to show the immunomodulatory effect of progesterone on the inflammation of uterine tissue triggered by dysbiotic vaginal microbiota in a pregnant mouse model.Methods Healthy (n = 6) and dysbiotic (n = 7) vaginal microbiota samples isolated from pregnant women were transferred to control (n = 10) and dysbiotic (n = 14) pregnant mouse groups. The dysbiotic microbiota transferred group was treated with 1 mg progesterone (n = 7). Flow cytometry and immunohistochemistry analyses were used to evaluate inflammatory processes. Vaginal microbiota samples were analyzed by 16 S rRNA sequencing.Results Vaginal exposure to dysbiotic microbiota resulted in macrophage accumulation in the uterus and cellular damage in the placenta. Even though TNF and IL-6 elevations were not significant after dysbiotic microbiota transplantation, progesterone treatment decreased TNF and IL-6 expressions from 49.085 to 31.274% (p = 0.0313) and 29.279-21.216% (p = 0.0167), respectively. Besides, the macrophage density in the uterus was reduced, and less cellular damage in the placenta was observed.Conclusion Analyzing the vaginal microbiota before or during pregnancy may support the decision for initiation of progesterone therapy. Our results also guide the development of new strategies for preventing preterm birth.
