The Effect Of DMPA In The Rat Model Of Endometriosis

Background： Endometriosis is a common disease in reproductive-age women,however, its etiology and pathogenesis remain unclear. Previous studies indicated thatcytokine-mediated inflammatory responses may play a vital role in endometriosis. Inaddition, some studies found that Depot Medroxyprogesterone Acetate (DMPA), aneffective progestin in the treatment of endometriosis, may have a detrimental effect onbone mineral density (BMD).Objective: To establish SD rat model of endometriosis and evaluate the effect ofDMPA on it by assessing the expression of cytokine (IL-6and TNF-α) in peritonealfluid, BMD and bone biochemical metabolic markers, furthermore, to explore themechanism of Endometriosis.Methods: Using autologous transplantation of endometrium to establish rat model ofendometriosis.40rats of endometriosis were randomized into four groups. Group Awas EMs+sterile water (n=10), group B was EMs+L-DMPA (n=10), group C wasEMs+M-DMPA (n=10), group D was EMs+H-DMPA (n=10). Groups with DMPAwere experimental group while group A was control group. DMPA wereintramuscularly injected (every five days, six times in total) into the left thigh of therat and the dosage of DMPA in group B, C and D were0.025ml/kg×6.25,0.05ml/kg×6.25and0.1ml/kg×6.25, respectively. Group A were injected withsterile water (0.05ml/kg×6.25). Finally, endometrial cysts, serum estradiol levels,peritoneal fluid levels of IL-6/TNF-α, BMD(lumbar spine、femur、total body) andbone biochemical markers（CTX-I、NTX-I、PINP、BALP） before and after treatmentof DMPA were evaluated.Results:①serum estradiol levels in group B, C and D were significantly lowerthan group A after DMPA treatment (P<0.05).②The endometrial cysts in group B, Cand D reduced significantly after DMPA treatment (P<0.05) while no difference wasfound in group A.③peritoneal fluid levels of IL-6/TNF-α in DMPA groupsdecreased significantly (P<0.05) and, significant difference were found among DMPA groups and control group (P<0.05).④BMD of the whole body, femur, lumbar spinein each group were indifferent before and after DMPA treatment （P>0.05）.Nevertheless, lumbar spine BMD in group D reduced slightly after DMPA treatment（P>0.05）.⑤Bone biochemical markers: Serum levels of biochemical markers(CTX-I, NTX-I, PINP and BALP) in group A and B were indifferent after treatment（P>0.05）. While in group C and D, bone resorption (NTX-I/CTX-I) were increasedalong with bone formation (PINP/BALP) decreased (P <0.05). In addition, in group Cand D, bone resorption (NTX-I/CTX-I) were negatively correlated with serumestradiol levels (r=-0.513，-0.723；P <0.05) and bone formation (PINP/BALP) werepositively correlated with estradiol（r=0.688，0.626；P <0.05）.Conclusion:①the rat model of endometriosis using autologous transplantation ofendometrium could be a good animal model in studying endometriosis.②our studyindicated that DMPA could significantly inhibit the growth of ectopic endometrium.③DMPA could reduce levels of IL-6/TNF-α in peritoneal fluid by altering peritonealenvironment and attenuating inflammation.④the effect of DMPA on bone may becorrelated with low estradiol and, there may be a “threshold” for the effect of estradiolon bone, which means that bone resorption increased and bone formation decreasedwhen serum estradiol levels lower than “threshold” values caused by moderate or highdoses of DMPA and moreover, the much lower serum estradiol, the much earlierchange in BMD.