Male adolescent exposure to endocrine-disrupting pesticides: vinclozolin exposure in peripubertal rabbits.

Abstract

Adolescence is a time of dramatic neuroendocrine changes that are required for sexual maturation. Hormonal mimicking or inhibiting chemicals can cause significant impairment during this critical period. Vinclozolin (Vin) has been shown to be an anti-androgen affecting male offspring in rats in utero, and its mechanism of action may be mediated by inhibition of androgenic receptor action. The majority of teenagers working on farms are male, and therefore a systemic fungicide, vinclozolin, was selected for study. The rabbit has proved to be an excellent species for modelling reproductive toxicant effects in the male and was selected as the test species. The peripubertal phase for the rabbit was determined to be between the 3rd and 4th months. A 2-month dosing period was therefore initiated at 3 months of age and carried through to the 4th month. Vin was administered by dermal application (100 mg kg(-1) in 100 microl of dimethylsulphoxide) daily. Body weights were determined weekly. The rabbits were then held until fully mature (6 months of age). Semen was collected and evaluated from sexually mature males on a weekly schedule for 5 weeks to maximize sperm output. An automated solid phase extraction procedure for monitoring exposures through isolation and quantification of Vin and its metabolic products was developed. Increased plasma levels of Vin and M2 were found throughout the experimental period. The exposed rabbits had a smaller weight gain during pubertal growth (approaching significance; P=0.059). At maturity, the accessory sex glands of the exposed animals weighed less than those of the controls (P=0.016). Surprisingly, the pooled sperm count of the exposed animals was significantly higher (P=0.017) than that of the unexposed animals. The anti-androgenic effects of Vin may have blocked the negative feedback mechanism of testosterone on the hypothalamus or pituitary gland, allowing for an increase in gonadotrophin release, and consequently increasing sperm production at puberty.