Humans go through a 12-14 yr infantile period before final differentiation of the reproductive system during puberty. We hypothesize that exposure of humans to toxins, even at low concentrations, during infancy alters development of reproductive function, but remains undetected until after sexual maturity or advanced age. In conventional animal models (mice and rats) the infantile period is <15 days in males and pubertal differentiation starts before weaning. Sequelae of postnatal exposure to low levels of toxins in a species with a prolonged infantile period are unknown. This project will determine if exposure to contaminated water during the infantile period of development alters differentiation of the reproductive system or reproductive function in adults, or serves to enhance deleterious actions of a known reprotoxin.
The specific aims are to determine: (1) Long-term reproductive sequelae of postpubertal exposure to a chemical mixture, (2) Long-term reproductive sequelae of Device-prenatal plus infantile exposure to a chemical mixture, and (3) if exposure to a chemical mixture prior to or during infancy makes more deleterious or enhances the effect of a known reprotoxin. The same chemical mixture (arsenic, benzene, chloroform, chromium, lead, phenol, trichlorethylene) will be used for all aims.
Aim 1 will use male rats from Project 5, treated from 6 wk through 6-24 mo with 1 of 4 doses. A factorial experiment will provide male rabbits for Aims 2 and 3. Factors are: concentration of chemical mixture in drinking water from day 15 of gestation to 15 wk postnatal, reprotoxin treatment from birth to 15 wk postnatal, and age at evaluation. The reprotoxin will be zeranol, an estrogenic mycotoxin. Subjective and quantitative histological evaluations will be augmented by immunohistochemistry, in situ hybridization, and electron microscopy. Functionality of sperm will be ascertained. Follow- up studies will study alternative chemical mixtures or reprotoxins, effects of gender, and mechanisms by which damage is induced or expressed.
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