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The aim of this study was to evaluate the effect of rapamycin on decidual cell subpopulations and endometrial function in physiological and induced senescence and to investigate the decidual cell subpopulations present in physiological conditions during early pregnancy and implantation in mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Control, physiological decidualization (0.5\u00a0mM cAMP and 1\u00a0\u03bcM MPA added), and induced senescence (0.1\u00a0mM HU added) models with and without 200\u00a0nM rapamycin treatment were established using a human endometrial stromal cell line, and decidual cell subpopulations were analyzed by immunofluorescence and flow cytometry. The human extravillous trophoblast cell line AC-1M88 was also cultured in decidualization models, and spheroid expansion analysis was performed. In in vivo studies, decidual cell subpopulations were analyzed by immunofluorescence during early mouse pregnancy.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>The results revealed that rapamycin decreased DIO2 and \u03b2-GAL expressions in physiological and induced senescence without FOXO1. Notably, in induced senescence, increased fragmentation was observed in AC-1M88 cells, and rapamycin treatment successfully attenuated the fragmentation of spheroids. We showed that the FOXO1-DIO2 signaling axis can trigger decidual senescence during early gestation and days of implantation in mice.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our study underlines the importance of rapamycin in modulating decidual cell subpopulations and endometrial tissue function during decidual senescence. The information obtained may provide insight into the pathologies of pregnancy seen due to decidual senescence and guide better treatment strategies for reproductive problems.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s10815-024-03207-5","type":"journal-article","created":{"date-parts":[[2024,7,27]],"date-time":"2024-07-27T04:01:52Z","timestamp":1722052912000},"page":"2441-2456","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Deciphering the role of rapamycin in modulating decidual senescence: implications for decidual remodeling and implantation failure"],"prefix":"10.1007","volume":"41","author":[{"given":"Remziye","family":"Kendirci-Katirci","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leyla","family":"Sati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-8680","authenticated-orcid":false,"given":"Ciler","family":"Celik-Ozenci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,7,27]]},"reference":[{"issue":"7","key":"3207_CR1","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1038\/nrc3960","volume":"15","author":"NE Sharpless","year":"2015","unstructured":"Sharpless NE, Sherr CJ. 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