This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Goyal, H. O. Articles by Williams, J. W. Search for Related Content PubMed PubMed Citation Articles by Goyal, H. O. Articles by Williams, J. W.

Permanent Induction of Morphological Abnormalities in the Penis and Penile Skeletal Muscles in Adult Rats Treated Neonatally With Diethylstilbestrol or Estradiol Valerate: A Dose-Response Study

TIM D. BRADEN

JOHN W. WILLIAMS

From the Departments of ^* Biomedical Sciences and Biology/CBR/RCMI, Tuskegee University, Tuskegee, Alabama; and the Department of Anatomy, Physiology, and Pharmacology, Auburn University, Auburn, Alabama.

Correspondence to: H. O. Goyal, Department of Biomedical Science, School of Veterinary Medicine, Tuskegee University, Tuskegee, AL 36088 (e-mail: goyalho{at}tuskegee.edu).

This study evaluated the effects of neonatal exposure to different doses of diethylstilbestrol (DES) or estradiol valerate (EV) on penile morphology, penile skeletal muscles, and fertility. Male pups received DES or EV at a dose of 10 µg, 1 µg, 100 ng, 10 ng, or 1 ng per rat on alternate days from postnatal days 2-12. Fertility was tested at 120 days, and tissues were examined at 150 days. Generally, DES and EV induced similar effects within the 10- and 1-µg groups. Fertility was reduced to 0; the weight, length, and diameter of the penis and the weight of penile skeletal muscles, especially bulbocavernosus muscle, were decreased (P < .05) in a dose-dependent manner; the preputial sheath was partially released or its release was delayed; testicular descent was delayed; and the cavernous spaces and smooth muscle cells in the corpora cavernosa penis were replaced by fat cells. Conversely, all of the above parameters were similar in controls and the lower dose groups, except in the 100-ng DES group, in which 4 of 7 males did not sire pups (compared with 1 of 7 in controls and 2 of 6 in the 100-ng EV group). The loss of fertility in these 4 males of the DES group and 1 male of the EV group was associated with partial release of the preputial sheath and abnormal penile morphology. Plasma testosterone was reduced (P < .05) in the 100-ng and higher dose groups for DES and EV. Hence, neonatal exposure to DES or EV at a cumulative dose of 600 ng per rat or more lowers fertility, which is associated with permanent alterations in penile morphology and penile skeletal muscles and decreased testosterone.

     Key words: Estrogen, DES, fertility, testosterone, bulbocavernosus

This article has been cited by other articles:

				E. Mathews, T. D. Braden, C. S. Williams, J. W. Williams, O. Bolden-Tiller, and H. O. Goyal Mal-Development of the Penis and Loss of Fertility in Male Rats Treated Neonatally with Female Contraceptive 17{alpha}-Ethinyl Estradiol: A Dose-Response Study and a Comparative Study with a Known Estrogenic Teratogen Diethylstilbestrol Toxicol. Sci., December 1, 2009; 112(2): 331 - 343. [Abstract] [Full Text] [PDF]

				H.O. Goyal, T.D. Braden, C.S. Williams, and J.W. Williams Estrogen-Induced Developmental Disorders of the Rat Penis Involve Both Estrogen Receptor (ESR)- and Androgen Receptor (AR)-Mediated Pathways Biol Reprod, September 1, 2009; 81(3): 507 - 516. [Abstract] [Full Text] [PDF]

				A. M. Traish Androgens Play a Pivotal Role in Maintaining Penile Tissue Architecture and Erection: A Review J Androl, July 1, 2009; 30(4): 363 - 369. [Abstract] [Full Text] [PDF]

				H O Goyal, T D Braden, C S Williams, and J W Williams Role of estrogen in induction of penile dysmorphogenesis: a review Reproduction, August 1, 2007; 134(2): 199 - 208. [Abstract] [Full Text] [PDF]

				H O Goyal, T D Braden, P S Cooke, M A Szewczykowski, C S Williams, P Dalvi, and J W Williams Estrogen receptor-{alpha} mediates estrogen-inducible abnormalities in the developing penis Reproduction, May 1, 2007; 133(5): 1057 - 1067. [Abstract] [Full Text] [PDF]

				H. O. Goyal, T. D. Braden, C. S. Williams, P. Dalvi, M. Mansour, and J. W. Williams Estrogen-Induced Abnormal Accumulation of Fat Cells in the Rat Penis and Associated Loss of Fertility Depends upon Estrogen Exposure during Critical Period of Penile Development Toxicol. Sci., September 1, 2005; 87(1): 242 - 254. [Abstract] [Full Text] [PDF]