Effects of in utero linuron exposure on rat Wolffian duct development

Abstract

Linuron is an herbicide that displays weak androgen receptor antagonist activity. Male offspring exposed in utero to 50 mg/kg/day linuron often exhibit malformations in Wolffian duct derivatives (i.e. the epididymis and vas deferens). The objectives of this study were to determine the point during the perinatal period that linuron-induced epididymal lesions can be identified, to characterize linuron-mediated perinatal testicular and epididymal pathology, and to determine whether male rat fetuses exposed prenatally to linuron exhibit decreased intratesticular and serum testosterone (T) levels. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day ( n = 3 controls, 5–11 linuron-treated dams per time point) from gestation days (GD) 12 to 21 or to termination. Male fetuses or offspring were necropsied on GD 17, 19, and 21, and postnatal days (PND) 7 and 14. Epididymal malformations were not observed in fetuses from linuron-treated dams but were seen in linuron-exposed male offspring on PND 7 and 14. No testicular lesions were observed at any time point. The growth and development of linuron-exposed fetuses were altered, as evidenced by slight decreases in fetal weight and increased levels of immunoreactive proliferating cell nuclear antigen (PCNA) on GD 21. Intratesticular and serum T levels were not decreased in linuron-exposed male fetuses. These findings indicate that the adversely altered adult phenotype following in utero exposure to linuron is very similar to that produced by the antiandrogens di- n-butyl phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP). However, the absence of testicular lesions or alterations in fetal testosterone levels would suggest that the effect of linuron on the developing Wolffian ducts is distinctly different from DBP or DEHP.