Estrogen receptor a has a functional role in the mouse rete testis and efferent ductules

Previous studies of the estrogen receptor-alpha knockout (alpha ERKO) in th e male mouse demonstrate that the rete testis and efferent ductules are tar gets of estrogen. Because the alpha ERKO mouse lacks a functional estrogen receptor alpha (ER alpha) throughout development, it was not known whether the morphological and physiological abnormalities observed in the aERKO mal e were due to developmental defects or to dysfunctions concurrent with the lack of ER alpha in the tissue. This study was designed to determine if tre atment of normal wild-type (WT) mice with the pure antiestrogen, ICI 182,78 0, (ICI) could reproduce the morphological characteristics seen in alpha ER KO mice. Thirty-day-old male mice were treated for 35 days with either cast or oil or ICI. Age-equivalent aERKO mice were used for comparison. Light mi croscopic examinations of the reproductive tracts revealed dramatic changes in the efferent ductules of treated mice: a 1.7-fold increase in luminal d iameter, a 56% reduction in epithelial cell height, a 60% reduction in brus h boarder height of nonciliated cells, and an apparent reduction of the num ber of observable lysosomes and endocytotic vesicles. Testes of ICI-treated mice showed swollen rete testes area (6.5 times larger than control) and a 65% reduction in rete testis epithelium height. However, there were no sig nificant changes in body and testis weights. These results indicate that ER blockage with ICI in WT mice results in morphological changes of the effer ent ductules resembling those seen in aERKO siblings of the same age. Based on this study, we conclude that ER alpha has a functional role in the mous e reproductive tract and the aberrant morphology observed in the efferent d uctules of the alpha ERKO mouse is likely the result of a concurrent respon se to the lack of functional ER alpha, and not solely due to the lack of ER alpha during early developmental times.