Effects of Neonatal Administration of Diethylstilbestrol in Male Hamsters: Disruption of Reproductive Function in Adults after Apparently Normal Pubertal Development1

Abstract

Prenatal and neonatal exposure to natural and synthetic estrogens induces developmental abnormalities in the male and female reproductive systems in several species. In hamsters, a single injection of diethylstilbestrol (DES) on the day of birth induces teratogenic and neoplastic changes throughout the female reproductive tract, apparently via a direct mechanism. The present study investigated the extent and specificity of this phenomenon in the male reproductive system. Male golden hamsters received injections of DES or estradiol-17beta (E2; 100 microg/ animal) on the day of birth and were then killed at 42 (pubertal) and 90 (adults) days of age. Blood was collected for serum testosterone analysis, and the testes and accessory organs were weighed and examined histologically. At the pubertal stage, testicular and accessory organ weights plus serum testosterone levels were similar in untreated animals and in both groups of estrogen-treated animals. Also at the pubertal stage, initiation of spermatogenesis appeared normal in both groups of estrogen-treated animals. In contrast, 100% of the DES-treated animals (n = 22) but none of the E2-treated animals exhibited multiple lesions in the reproductive tract as adults. These DES-induced lesions included cryptorchidism with the testes attached to the abdominal wall, solid testicular tumors, multiple epididymal cysts, and involution of accessory organs. Spermatogenesis was disrupted in the seminiferous tubules, with no developing germ cells, and the interstitial cells were organized as a sheath around the dysfunctional tubules. The epididymis had an involuted epithelial layer with a preponderance of multi-nucleated cells, and seminal vesicle morphology was also abnormal. These DES-specific alterations were not accompanied by any significant change in circulating testosterone levels. We therefore conclude that 1) DES is much more potent that E2 as a neonatal endocrine disrupter in the male hamster, and 2) the DES-specific lesions in the adult male reproductive tract may represent a permanently altered androgen responsiveness in the affected target tissues.

Morphometric studies of neonatal estrogen imprinting in the mature mouse prostate

“…In addition, exposure to low sex steroid concentrations due to fetal position in utero, may modify structure and function of the mature prostate (vom Saal 1981(vom Saal , 1989. Developmental exposure to DES evokes long-term effects in a wide range of tissues such as disruption of reproductive function in adult rats (Khan et al 1998), induction of long-range changes in the uterine target cells (Newbold et al 1990) and alteration of bone density in female mice (Migliaccio et al 1992(Migliaccio et al , 1995. Neonatal estrogenization also increases prostatic protooncogene expression (Salo et al 1997) and decreases cytosolic estrogen (Turner et al 1989) and prolactin (Edery et al 1990) receptor levels in rodent VP.…”

“…However, no response to DES was observed in the uteri of estrogen receptor knock-out (ERKO) mice (Korach & Couse 1996) indicating that the estrogen receptor may be the main signaling pathway for the hormonal agonist activity of DES. A recent study of DES and estradiol effects in male hamsters described severe disruption of reproductive function with neonatal DES (Khan et al 1998) which was attributed to lasting damage to the target tissue resulting in aberrant response to normal endocrine signals. Alternatively, DES effects may possibly be mediated by other mechanisms in addition to its interaction with estrogen receptors, like production of toxic metabolites (Korach et al 1978).…”

Comparative Toxicity Study of 3-Aminophenol in Newborn and Young Rats

“…While unique and/or higher toxicity of some chemicals in infants has recently been reported (Lee, 1998;Khan et al, 1998;Katsuda et al, 2000), there is no systematic toxicity study protocol to examine direct toxic effects of chemicals in newborn animals. Although the results of one-and/or two-generation studies might reflect the toxicity of chemicals in infants exposed from the neonatal period to weaning, the exposure occurs only via their maternal milk.…”

Effects of Postnatal Administration of Diethylstilbestrol on Puberty and Thyroid Function in Male Rats

“…55: [461][462][463][464][465][466] 2009) oncerns have been raised about the potential adverse effects of environment chemicals that mimic the actions of estrogen on the reproduction and development of humans and wildlife species. Exposure of the developing male to exogenous estrogenic compounds can result in reproductive and developmental abnormalities and an increase in human male reproductive disorders, which include testicular cancer, cryptorchidism, hypospadias and low sperm counts [1][2][3][4]. Neonatal treatment with estrogens causes alterations in germ cell development and permanent impairment of testicular function [5][6][7][8][9].…”