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Gestational Exposure to Atrazine: Effects on the Postnatal Development of Male Offspring

VASSILIOS PAPADOPOULOS

From the ^* Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; and the Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC.

Correspondence to: Dr Barry R. Zirkin, Division of Reproductive Biology, Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 (e-mail: brzirkin{at}jhsph.edu).

Atrazine is an herbicide used worldwide to control grasses and weeds. Previous studies have shown that, depending on atrazine's administered dose, exposure of male rats during the early postnatal or peripubertal periods can result in alterations in endocrine function. The gestational period is particularly vulnerable to environmental agents; however, the possible effects of atrazine exposure during this period have received only limited attention. Herein we examine the dose effects of atrazine exposure during Sprague-Dawley rat gestation on the postnatal development of male offspring. Pregnant dams were treated by oral gavage with atrazine at 0 to 100 mg/kg/d from gestational day 14 to parturition. Thereafter, neither the pups nor the dams received atrazine. Atrazine had no effect on the number of live births per dam. Neonatal pup survival was affected, however, with increased pup death seen at doses of 10 mg/kg/d and higher. There was no effect of atrazine on the testosterone concentration within the testes of newborn pups. Anogenital distance, an androgen-dependent process, decreased from the control level at the 75 and 100 mg/kg/d doses, with the decrease reaching significance at 100 mg/kg/d. Preputial separation, also an androgen-dependent process, was delayed significantly compared with that in controls in response to the 50 and 100 mg/kg/d doses. At postnatal day 60, serum testosterone concentrations were reduced significantly from controls in the 50 to 100 mg/kg/d groups. However, these decreases had little effect on seminal vesicle or ventral prostate weights. These results, taken together, are suggestive of antiandrogenic effects of gestational atrazine exposure on male offspring, although for most parameters, the doses used in this study are unlikely to be experienced under any but experimental conditions.

     Key words: Gestation, Leydig cells, steroidogenesis, antiandrogen