Estrogen-Induced Abnormal Morphology of the Penis, Altered Sexual Behavior and Loss of Fertility in Male Rats

Penile abnormalities, including hypospadias and/or smaller phallus, have been reported in laboratory animals and alligators exposed to estrogenic chemicals, as well as in offspring of women treated with diethylstilbestrol (DES) during pregnancy. In addition, estrogen receptors have been identified in the penis; however, the mechanism of estrogen action in inducing penile abnormalities is not clear. In this study we determined whether reduced fertility and altered sexual behavior in adult rats treated with (DES) neonatally or at adulthood are associated with structural changes in the penis and whether testosterone (T) supplementation can reverse the effects of DES. Plasma T was significantly decreased (P < 0.05), whether DES was given neonatally or at adulthood. The penile morphology was adversely affected in rats that received DES neonatally, including reductions in length, diameter and weight of the penis, and complete replacement of cavernous spaces with fat cells in the body of the penis. None of the neonatal DES-treated males (0/6) sired a pup or produced a copulatory plug, in contrast to 6/7 in controls. Supplementation with T restored penile morphology and sexual behavior (as indicated by the presence of copulatory plugs, 6/6) to an almost normal level, but fecundity (ability to sire pups, 3/6) only partially. Conversely, penile morphology was not altered in rats that received DES at adulthood, although adverse effects on sexual behavior and fecundity, and their prevention by T supplementation, were similar to those of the neonatal group. Hence, neonatal estrogen exposure, but not adult estrogen exposure, leads to abnormal morphology of the penis; however, both exposures result in reduced fertility and altered sexual behavior. Supplementation with T prevents many estrogen-induced effects.