| Adenomyosis is a common gynecologic disorder with a poorly understood pathogenesis. It is defined as the presence of heterotopic endometrial glands and stroma in the myometrium. The presenting symptoms include a soft and diffusely enlarged uterus, menorrhagia, dysmenorrheal, and subfertility. Treatment of adenomyosis has been a challenge, with hystereetomy being the most useful treatment by now.An epithelial-mesenchymal transition (EMT) is a biologic process that allows a polarized epithelial cell, which normally interacts with basement membrane via its basal surface, to undergo multiple biochemical changes that enable it to assume a mesenchymal cell phenotype, which includes enhanced migratory capacity, invasiveness, elevated resistance to apoptosis, and greatly increased production of ECM components.The biological behavior of adenomyosis is somewhat similar to the EMT. In this study, we investigate the relationship between this two to find out the possible pathology of adenomyosis.Part I The animal model of adenomyosis induced by TAMObejectives:To establish an animal model with mice and TAM.Methods:Six to seven pregnant ICR mice will be used and maintained in the lab. Their newborn female pubs will be equally divided, at random, into 2 groups:one receiving oral dosing on days 1-5 after birth (day of birth being day 0) with 1 mg/kg tamoxifen (TAM), and the other group receiving vehicle only. Five female mice each will be culled on days 5,10,15,42, and 60, and uterine tissue will be harvested. Uteri will be fixed in 4% neutral buffered formalin for 24 h at room temperature. Paraffin-embedded cross sections (4 μm thin) will be cut and mounted on salane-coated glass slides for histological and immunohistochemical examination. On days 28,42 and 56, all mice will be administrated a hotplate test to measure response to noxious thermal stimulus.Results:H-E staining of the mouse uterine slides showed heterotopic endometrial glands and stroma in the myometrium at the day of 10,15,42, and 60. Hotplate test showed a downward trend of both groups, while the one receiving TAM showed a significant difference.Conclusion:TAM can cause adenomyosis in ICR mouse. The success rate is 100% at day 42. During the modeling, the pain sensitivity increased.Part II The effect of EMT in adenomyosisObjectives:To investigate the relationship between EMT and adenomyosis.Methods:Ectopic endometrium from 14 women with adenomyosis and endometrium from 20 age- and menstrualphase-matehed women without adenomyosis were used for immunohistoehemical of E-cadherin, vimentin, TGF-β, Sixl and p-Smad3. So were the slides of mouse uterine.Results:Compared with normal endometrium, E-cadherin immunoreactivity were significantly reduced in ectopic endometrium from women with adenomyosis(P<0.05), while the vimentin, TGF-β, Sixl and p-Smad3 immunoreactivity were significantly increased(P<0.05).E-cadherin immunoreactivity of mice receiving TAM were significantly reduced from day 5 to day 60, while the mice receiving vehicle only didn’t change, but were significantly positive than the TAM ones. The vimentin, TGF-β, Sixl and p-Smad3 immunoreactivity were the opposite.Conclusion:EMT played a role in adenomyosis.Part Ⅲ The relationship between EMT induced fibrosis and adenomyosisObejectives:To investigate the relationship between EMT induced fibrosis and adenomyosis.Methods:Ectopic endometrium from 14 women with adenomyosis and endometrium from 20 age- and menstrualphase-matehed women without adenomyosis were used for immunohistoehemical of α-SMA and collagen Ⅰ. Masson staining and picro-sirius red staining were also performed. So were the slides of mouse uterine.Conclusions:Fibrosis happened in adenomyosis, and EMT may played a role in it. |
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