Neonatal low- and high-dose exposure to estradiol benzoate in the male rat: II. Effects on male puberty and the reproductive tract

Environmental contaminants with estrogenic properties have been cause for h eightened concern about their possible role in inducing adverse health effe cts. Brief exposure of rodents to high doses of natural estrogens early in life results in permanent alterations of the male reproductive tissues, but the question of whether environmentally relevant doses can cause the same effects remains controversial. The current project was designed to determin e the dose-response relationship between neonatal estradiol exposure and th e development of the male reproductive tract in the rat. Neonatal male Spra gue-Dawley (SD) and Fisher 344 (F344) rats were exposed to O-estradiol-3-be nzoate (EB) at concentrations ranging from 0.015 mug/kg body weight (BW) to 15.0 mg/kg BW and 0.15 mug/kg BW to 1.5 mg/kg BW, respectively. Results sh owed an inverted U-shaped dose-response profile for testis and epididymis w eights in 35-day-old SD rats, with increased organ sizes at the low-dose en d of the treatment. This effect was transient and was not sustained into ad ulthood. Increased hepatic testosterone hydroxylase activities in low-dose animals suggest an advancement of puberty as the cause for increased reprod uctive organ weights. On postnatal day (PND) 90, a stimulatory low-dose res ponse to EB was present in SD rat testicular and epididymal weights, howeve r at one order of magnitude lower dose than that seen on PND 35, suggesting a separate effect. All SD male reproductive tract organs and serum hormone s showed a permanent inhibitory response to high doses of neonatal EB. F344 rats exhibited greater estrogen sensitivity on PND 90. Despite this height ened responsiveness, F344 rats did not exhibit a low-dose effect for any en dpoint. These low-dose responses to estradiol are organ and strain specific .