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BOR - Papers in Press, published online ahead of print January 28, 2004.
Biol Reprod 2004, 10.1095/biolreprod.103.026328
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BIOLOGY OF REPRODUCTION 70, 1504–1517 (2004)
DOI: 10.1095/biolreprod.103.026328
© 2004 by the Society for the Study of Reproduction, Inc.

Reproductive Technology

Abnormal Morphology of the Penis in Male Rats Exposed Neonatally to Diethylstilbestrol Is Associated with Altered Profile of Estrogen Receptor-{alpha} Protein, but Not of Androgen Receptor Protein: A Developmental and Immunocytochemical Study1

H.O. Goyal2,3, T.D. Braden5, C.S. Williams3, P. Dalvi3, M.M. Mansour3, M. Mansour3, J.W. Williams4, F.F. Bartol6, A.A. Wiley6, L. Birch7, and G.S. Prins7

Departments of Biomedical Sciences3 Biology/CBR/RCMI,4 Tuskegee University, Tuskegee, Alabama 36088 Departments of Anatomy, Physiology, and Pharmacology,5 and Animal Sciences, Cellular and Molecular Biosciences Program,6 Auburn University, Auburn, Alabama 36849 Department of Urology,7 University of Illinois, Chicago, Illinois 60612

Objectives of the study were to determine developmental changes in morphology and expression of androgen receptor (AR) and estrogen receptor (ER){alpha} in the body of the rat penis exposed neonatally to diethylstilbestrol (DES). Male pups received DES at a dose of 10 µg per rat on alternate days from Postnatal Day 2 to Postnatal Day 12. Controls received olive oil vehicle only. Tissue samples were collected on Days 18 (prepuberty), 41 (puberty), and 120 (adult) of age. DES-induced abnormalities were evident at 18 days of age and included smaller, lighter, and thinner penis, loss of cavernous spaces and associated smooth muscle cells, and increased deposition of fat cells in the corpora cavernosa penis. Fat cells virtually filled the entire area of the corpora cavernosa at puberty and adulthood. Plasma testosterone (T) was reduced to an undetectable level, while LH was unaltered in all treated groups. AR-positive cells were ubiquitous and their profile (incidence and staining intensity) did not differ between control and treated rats of the respective age groups. Conversely, ER{alpha}-positive cells were limited to the stroma of corpus spongiosus in all age groups of both control and treated rats, but the expression in treated rats at 18 days was up-regulated in stromal cells of corpora cavernosa, coincident with the presence of morphological abnormalities. Hence, this study reports for the first time DES-induced developmental, morphological abnormalities in the body of the penis and suggests that these abnormalities may have resulted from decreased T and/or overexpression of ER{alpha}.

1 Supported by NIH grants MBRS-5-S06-GM-08091 (to H.G.) and RCMI- 5-G128803059 and by USDA grant CSR-EES-ALX-TU-CTIF.

2 Correspondence: H.O. Goyal, Department of Biomedical Sciences, School of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088. FAX: 334 727 8177; goyalho{at}tuskegee.edu




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