Time-associated changes in protein expression following dienogest treatment in a mouse model of adenomyosis

In: BMC Women's Health · 2026 · doi:10.1186/s12905-026-04930-0 · W7220995528
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Dienogest treatment in a mouse model of adenomyosis induced time-dependent changes in EMT markers, hormone receptors, and inflammatory proteins, with short-term intervention showing regulatory effects that attenuated after six weeks.

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This study utilized a tamoxifen-induced mouse model to examine temporal changes in epithelial–mesenchymal transition markers, hormone receptors, and inflammatory proteins following dienogest treatment. The results indicated that short-term intervention for two to four weeks downregulated specific inflammatory and EMT-related proteins while altering progesterone receptor expression. However, extending the treatment to six weeks resulted in an attenuation of these beneficial effects, with increased IL-6 levels and decreased E-cadherin, suggesting potential long-term complications such as receptor desensitization. The authors note that direct evidence for these mechanisms is lacking and that further research is required to fully elucidate the underlying tissue-level changes. This paper is centrally about adenomyosis, specifically investigating the time-dependent efficacy and molecular impacts of dienogest therapy in an experimental animal model.

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Abstract

This 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. A 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. Compared 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 (P0.05). 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 (P0.05). Short-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.
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Abstract

Introduction This 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.

Methods

A 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.

Results

Compared 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 (P0.05). 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 (P0.05).

Conclusion

Short-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. Similar content being viewed by others

Acknowledgements

The authors would like to thank all participants who contributed to this study. Funding All authors were supported by the Li Weixian Famous Doctor Studio of Guangdong Provincial Hospital of Traditional Chinese Medicine, grant number E43719. Author information Authors and Affiliations Corresponding authors Ethics declarations Ethics approval and consent to participate This 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. Consent for publication Not applicable. Competing interests The authors declare no competing interests. Additional information Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Rights and permissions Open 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/. About this article Cite this article Lin, 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 Received: Accepted: Published: DOI: https://doi.org/10.1186/s12905-026-04930-0

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