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(But Not Estrogen Receptor ß) during Postnatal Development of the Epididymis and Vas Deferens of the Rat and Disruption of This Pattern by Neonatal Treatment with Diethylstilbestrol1
Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology (N.A., C.M., K.W., K.J.T., J.S.F., P.T.K.S., M.R.M., R.M.S.), Edinburgh, Scotland EH3 9ET; and Institute of Experimental Morphology and Anthropology, Bulgarian Academy of Science (N.A.), 1113 Sofia, Bulgaria
Address all correspondence and requests for reprints to: Dr. R. M. Sharpe, Medical Research Council Human Reproductive Sciences Unit, Center for Reproductive Biology, 37 Chalmers Street, Edinburgh, Scotland EH3 9ET. E-mail: r.sharpe{at}hrsu.mrc.ac.uk
This study in rats sought to 1) characterize immunoexpression of
estrogen receptor 
(ER) and ERß in the efferent ducts,
epididymis, and vas deferens during postnatal development; 2) establish
whether ER expression changed after neonatal treatment with
diethylstilbestrol (DES); and 3) determine whether ER changes coincided
with abnormal epididymal/vas development. Rats were administered 10
µg DES or vehicle on days 2, 4, 6, 8, 10, and 12 and were sampled on
days 10, 18, 25, 35, and 90+. At all ages, ER was immunoexpressed
intensely in the efferent ducts. On day 10, immunoexpression of ER
was absent from the epididymis and vas, but was detectable on day 18 in
epithelial cells in the caput, corpus, and proximal cauda. Epithelial
expression of ER was absent from the distal cauda and in the
proximal and distal vas was confined to a band of periductal stromal
cells. Thus, on day 18, the site of ER expression delineated the
epididymis-vas boundary. On days 25–35, epithelial expression of ER
was absent, but stromal expression persisted in the vas and distal
cauda. In adults, immunoexpression of ER in the epididymis and vas
was absent. In contrast, ERß was immunoexpressed in epithelial cells
and some stromal cells in the efferent ducts, epididymis, and vas at
all ages. In the vas, stromal expression of ER and ERß was in
different layers.
DES treatment caused 1) underdevelopment of the epididymal duct and
reduced epithelial height in epididymis and vas; 2) coiling of the
extraepididymal vas; 3) thickening of the periductal actin-free stromal
layer in the distal cauda and vas; and 4) reduced cell proliferation on
day 18 in the epididymis and vas, based on incorporation of
bromodeoxyuridine, especially in the epithelium. These changes
coincided with abnormalities in cell- and region-specific
immunoexpression of ER, but not ERß. Thus, in DES-treated rats on
day 18, epithelial expression of ER occurred in all regions of the
epididymis and vas instead of being confined to the caput, corpus, and
proximal cauda as in controls. Similarly, stromal ER expression in
the vas of DES-treated rats was not confined to a periductal layer as
in controls, but occurred diffusely in the muscle layer. It is
suggested that 1) estrogens play a role in peripubertal development of
the epididymis and vas; 2) the cellular site of expression of ER
either plays a role in or reflects demarcation of the epididymal/vas
boundary; and 3) blurring of this boundary in DES-treated rats
coincides with altered ER immunoexpression.
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