Neonatal feeding of an estrogen receptor β agonist induces external adenomyosis-like lesions in ICR mouse  

作　　者：Yun-Lei Cao Xi Wang Xi-Shi Liu Tasuku Harada Sun-Wei Guo 

机构地区：[1]Shanghai Obstetrics and Gynecology Hospital,Fudan University,Shanghai 200011,China [2]Shanghai Key Laboratory of Female Reproductive Endocrine-Related Diseases,Fudan University,Shanghai 200011,China [3]Department of Obstetrics and Gynecology,Tottori University Faculty of Medicine,Yonago,Tottori 683-8504,Japan

出　　处：《Reproductive and Developmental Medicine》2022年第3期144-151,共8页生殖与发育医学（英文版）

基　　金：funded in part by grants 81771553(S.G.),82071623(S.G.),and 81871144(X.L.)from the National Science Foundation of China;an Excellence in Centers of Clinical Medicine grant(2017ZZ01016)from the Science and Technology Commission of Shanghai Municipality;Clinical Research Plan grant SHDC2020CR2062B from Shanghai Shenkang Center for Hospital Development.

摘　　要：Objective:Despite the fact that adenomyosis is a fairly common gynecological disorder,its pathogenesis remains elusive.Several theories on the pathogenesis of adenomyosis have been proposed,but none of them has been proven experimentally.So far,the most used one is the neonatal feeding of tamoxifen(TAM)in Institute of Cancer Research/cryopreserved(ICR/CD-1)mouse.However,its underlying mechanism of action is unknown.To further delineate the mechanism of TAM-induced adenomyosis in ICR/CD-1 mouse with regard to specific estrogen receptor(ER),we conducted an experiment that neonatal mice were fed with either TAM,or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl)trisphenol(PPT;an ERαagonist),or 2,3-bis(4-hydroxyphenyl)-propionitrile(DPN;an ERβagonist),or G-1(a G-protein coupled receptor 30 agonist),or just vehicle,in an attempt to tease out which specific receptor plays a dominant role in the genesis of adenomyosis induced by neonatal feeding of TAM.Methods:Forty female neonatal mice were randomly divided into 5 equal-sized groups:CTL(control),TAM,PPT,DPN,and G-1.Three months later,all mice were sacrificed and their uterine horns were harvested,weighed,and processed for histological evaluation.Results:All mice in the TAM group developed adenomyosis,so did 4 mice(50%)in the DPN group,a result that should be considered significant given that mice in the CTL group would not develop adenomyosis.No mouse in the PPT or G-1 group developed adenomyosis.Remarkably,all lesions in the DPN group were seen exclusively near the uterine serosa,which are dramatically different from that of TAM mice and reminiscent of extrinsic or external adenomyosis in humans.Conclusions:Neonatal feeding of DPN induces adenomyosis,but the adenomyotic lesions appear to be different from those induced by TAM.Thus,the cause of TAM-induced adenomyosis in ICR/CD-1 mouse cannot be attributable to one specific ER alone.This suggests that the extrinsic/external adenomyosis may have a pathogenesis that is different from other sub-types of adenomyosis.

关 键 词：ADENOMYOSIS Estrogen receptor a agonist Estrogen receptorβagonist Mouse model NEONATAL TAMOXIFEN 

分 类 号：R711.74[医药卫生—妇产科学]