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

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 (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). 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.