{"paper_id":"c8ae5e4c-4e40-4c3e-a177-9dba381720bc","body_text":"Abstract\nIntroduction\nThis study aimed to investigate temporal changes in epithelial–mesenchymal transition (EMT), hormone receptor balance, and inflammatory markers at the tissue protein level following dienogest (DNG) treatment in a mouse model of adenomyosis, and to propose preliminary hypotheses regarding the temporal differences in the expression of these proteins.\nMethods\nA mouse model of adenomyosis was established using tamoxifen. Following successful model establishment, the model and control groups received peanut oil by gavage, whereas the 2-, 4-, and 6-week DNG intervention groups received DNG at 0.303 mg/kg/day by gavage for 2, 4, and 6 weeks, respectively. At the end of each treatment period, the expression of E-cadherin, N-cadherin, ER, PR, IL-6, IL-1β, vimentin, NGF, and VEGF in uterine tissues was assessed by immunohistochemistry, followed by statistical analysis using the appropriate methods.\nResults\nCompared with the control group, the expression of N-cadherin, IL-1β, NGF, ER, Vimentin, IL-6, and VEGF in the uterine tissues of mice in the model group increased (P<0.05), E-cadherin decreased (P<0.05), and the difference in the expression of PR was not statistically significant (P>0.05). Compared with the model group, after 2 weeks of intervention with dienogest, the protein levels of NGF, Vimentin and VEGF were down-regulated (P<0.05), and the protein levels of PR and IL-6 were increased (P<0.05). After 4 weeks of intervention with dienogest, the expression levels of N-cadherin, NGF, ER, and E-cadherin were decreased (P<0.05). When the intervention was extended to 6 weeks, IL-6 expression level increased (P<0.05), and E-cadherin protein expression decreased, while there was no statistically significant difference compared with the 4-week intervention group (P>0.05).\nConclusion\nShort-term (2-4 weeks) DNG intervention appears to modulate EMT, exhibit a regulatory trend on hormone receptors, and temporarily alleviate the local inflammatory microenvironment. However, long-term (6 weeks) intervention suggests a potential attenuation of these observed effects, which may be related to the combined effects of multiple tissue-level changes, including altered progesterone receptor responsiveness, inflammatory microenvironment disorders, and the pathological progression of EMT. However, direct evidence for receptor desensitization or other specific mechanisms is currently lacking. This study merely observed changes in protein expression at the tissue level, further research is needed to elucidate the underlying mechanisms.\nSimilar content being viewed by others\nAcknowledgements\nThe authors would like to thank all participants who contributed to this study.\nFunding\nAll authors were supported by the Li Weixian Famous Doctor Studio of Guangdong Provincial Hospital of Traditional Chinese Medicine, grant number E43719.\nAuthor information\nAuthors and Affiliations\nCorresponding authors\nEthics declarations\nEthics approval and consent to participate\nThis study was approved by the Experimental Animal Ethics Committee of Jinan University, Guangdong Province, China (Approval No. IACUC-20230718-09), and the license for the use of experimental animals was SYXK (Guangdong) 2022 − 0174.\nConsent for publication\nNot applicable.\nCompeting interests\nThe authors declare no competing interests.\nAdditional information\nPublisher’s note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\nRights and permissions\nOpen Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.\nAbout this article\nCite this article\nLin, H., Yan, S., Lin, Y. et al. Time-associated changes in protein expression following dienogest treatment in a mouse model of adenomyosis. BMC Women's Health (2026). https://doi.org/10.1186/s12905-026-04930-0\nReceived:\nAccepted:\nPublished:\nDOI: https://doi.org/10.1186/s12905-026-04930-0","source_license":"CC0","license_restricted":false}