Alteration of behavioral sex differentiation by exposure to estrogenic compounds during a critical neonatal period: effects of zearalenone, methoxychlor, and estradiol in hamsters.

The present study was designed to determine if neonatal exposure to the estrogenic mycotoxin zearalenone or the weakly estrogenic pesticide methoxychlor could masculinize and/or defeminize the behavior of female hamsters. Neonatal hamsters were given a single sc injection of either zearalenone (1 mg/pup), methoxychlor (1 mg/pup), 17 beta-estradiol (E2) (40 micrograms/pup), or the vehicle 2 days after birth. After puberty, behavioral estrous cyclicity was measured. The females were then ovariectomized, treated with the male hormone testosterone, and tested for their ability to mount a receptive female (a behavior not normally displayed by female hamsters). Females treated neonatally with estradiol or zearalenone were masculinized but not defeminized, an effect consistent with perinatal exposure to low doses of sex hormones. Females in these two treatment groups displayed normal 4-day behavioral estrous cycles, but following ovariectomy and testosterone treatment they mounted a sexually receptive female at a frequency comparable to the males. Methoxychlor-treated females did not differ from controls. The mounting behavior of similarly treated males was unaffected by any of the chemicals. However, males receiving estradiol treatment had smaller testes, seminal vesicles, and cauda epididymides and 57% had epididymal cysts. These results demonstrate that a single exposure to a weakly estrogenic chemical like zearalenone during a critical developmental period can cause the brain to differentiate in a manner inconsistent with the female's genetic sex. This enables the female to respond to the activational influence of testosterone as an adult and readily mount a sexually receptive female. The failure of methoxychlor to alter reproductive development in the current study may be due to an inability of the neonatal hamster to convert methoxychlor to estrogenic metabolites.