Objective: To investigate the therapeutic mechanism of bazedoxifene, the third-generation selective ER modulator (SERM), on endometriosis lesions in a rat model.
Methods: Endometriosis was induced by transplanting pieces of endometrium from other syngeneic rats that were as donors onto the subcutaneous of other unmated female rats. The rats with successful ectopic implants were divided into two groups: control group (n=10) and bazedoxifene group (n=10). The macroscopic morphology, volume, histopathology of ectopic implant and rats uterine wet weight were determined before and after the treatment. Expression of proliferation cell nuclear antigen (PCNA), ER and PR in the eutopic endometrium and endometriosis lesions detected by immunohistochemistry in the two groups.
Results: (1) The gross morphology and histological changes of endometriosis lesions in rats after treatment: compared with the control group, it was obviously depauperated and had more less glands and blood vessels in the stroma. (2) The change of rats' weight, the volume of endometriosis lesion before and after treatment and rats uterine wet weigh after treatment respectively in the control group and the bazedoxifene group: rats' weight were respectively before treatment: (201±17) g, (202±18) g, that were respectively after treatment: (266±16) g, (261±16) g, which showed no significant difference between two groups before and after treatment (P>0.05). The volume of ectopic implant before treatment were respectively (85±17) mm3, (85±12) mm3, and showed no significant difference between two groups; that were respectively (48±11) mm3, (24±9) mm3 afte rtreatment, which was significantly decreased compared with the control group (P<0.05). Rats uterine wet weight after treatment were respectively: (0.77±0.16) g, (0.45±0.18) g, and was significantly reduced compared with the control group (P<0.05). (3) The protein expression levels of PCNA, ER and PR in the endometriosis lesions after treatment were respectively 0.282±0.044, 0.51±0.06, 0.49±0.05 in the control group, 0.191±0.020, 0.23±0.03, 0.48±0.06 in the bazedoxifene group; that in eutopic endometrium were respectively 0.369±0.081, 0.56±0.08, 0.56±0.10 in the control group, 0.211±0.037, 0.27±0.05, 0.54±0.08 in the bazedoxifene group; the protein expression levels of PCNA and ER in endometriosis lesions and the eutopic endometrium were significantly decreased in the bazedoxifene group compared with the control group (P<0.05), but the protein levels of PR in endometriosis lesionsand and the eutopic endometrium were not significantly altered by treatment (P>0.05).
Conclusion: Bazedoxifene could obviously reduce the size of endometriosis lesions, the mechanism may be related with suppressing estrogen-induced proliferation, the expression of ER and direct ER antagonism by this SERM.