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Neonatal Coadministration of Testosterone With Diethylstilbestrol Prevents Diethylstilbestrol Induction of Most Reproductive Tract Abnormalities in Male Rats

ANA RIVAS^*,

NINA ATANASSOVA

From the ^* MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Edinburgh, United Kingdom; the Laboratory of Medical Investigations, Department of Radiology, School of Medicine, HUSC-University of Granada, Granada, Spain; and the Institute of Experimental Morphology & Anthropology, Bulgarian Academy of Science, Sofia, Bulgaria.

Correspondence to: Dr R. M. Sharpe, MRC Human Reproductive Sciences Unit, Centre for Reproductive Biology, Chancellor's Building, The University of Edinburgh, 49 Little France Crescent, Old Dalkeith Rd, Edinburgh EH16 4SB, United Kingdom (e-mail: r.sharpe{at}hrsu.mrc.ac.uk).

The primary purpose of this study was to evaluate whether the coadministration of testosterone (TE; 200 µg) with 10 µg of diethylstilbestrol (DES) between days 2 and 12 postnatally could prevent the adverse gross reproductive tract changes and associated loss of androgen receptor (AR) expression induced by DES treatment alone. Various endpoints (rete testis area, efferent duct lumen area, epithelial cell height of efferent ducts, and vas deferens) were quantified to check for the abnormal changes that have been shown to occur after neonatal treatment with a high dose (10 µg) of DES. Additionally, DES induction of an aberrant pattern of estrogen receptor alpha (ER-) immunoexpression in the vas deferens and seminal vesicles was evaluated. The coadministration of DES with TE prevented the induction of all but one of the abnormalities induced by DES treatment on its own, coincident with the restoration of normal/supranormal TE levels and normal immunoexpression of the AR and ER- in the tissues studied. The exception was DES-induced lumenal distension of the efferent ducts, which was only partially prevented by the coadministration of DES with TE. These evaluations were made on day 18, but the described abnormalities were already somewhat evident by day 8 in DES-treated animals. It was therefore tested whether a delay of TE replacement until days 8–12 was still able to reverse the abnormalities already induced by DES treatment alone. A delayed treatment with TE reversed the adverse changes in epithelial cell height and in ER- and AR immunoexpression in the same tissues by day 18; however, rete testis overgrowth was only partially prevented, and efferent duct distension was not prevented at all. These results provide further evidence that DES-induced disorders of reproductive tract development in the male result from a disturbance of the androgen-estrogen balance rather than from estrogen action alone.

     Key words: Rete testis, efferent ducts, vas deferens, seminal vesicles, androgens, estrogens

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