The gestational exposure to the pesticide methoxychlor (m) inhibits testosterone (T) formation by neonatal rat Leydig cells (LC).
Derk-RC; Akgul-Y; Murono-EP
Toxicologist 2007 Mar; 96(1):116
M is a pesticide that has been used as a replacement for DTT because it is more rapidly cleared from the body and does not bioaccumulate. M has been reported to exhibit both weak estrogenic and antiandrogenic activities. Recent animal studies suggest that M or its dihydroxylated metabolite, HPTE, inhibits the ability of immature or adult rats to synthesize T. It is not known whether fetal LC present during the last third of pregnancy and for 1-2 weeks after birth in rodents, also are sensitive to M following in vivo exposure. The current studies evaluated whether the daily exposure by gavage of 0, 40, 100 or 200 mg/kg body weight of M dissolved in corn oil to pregnant Sprague-Dawley rats during days 14-22 of gestation, altered the capacity of neonatal (fetal) LC to produce T. Male pups were sacrificed on day 1 after birth, and the serum or testes from all male pups of each litter were pooled into a single sample. The pooled testes were digested with collagenase, and the dispersed LC were cultured in DMEM/F12 medium. Both basal and 10 mIU/ml hCG-stimulated T released into the medium was determined after culture for 4 h. There was a minimum of 11 determinations for each treatment group. Serum T level of animals exposed to 40 or 100 mg/kg M was no different than control; however, the T level declined to ~ 56 % of control in animals exposed to 200 mg/kg M. The basal T level of LC exposed in vivo to 40, 100 or 200 mg/kg M was no different than control. The hCG-stimulated T of LC from control animals was ~ 10.6 fold higher than the basal T from control animals, and the hCG-stimulated T of LC exposed to 200 mg/kg M declined to ~ 37 % of LC from control animals. These studies demonstrate that fetal LC exposed to a higher dose on M during the later third of gestation have reduced capacity to synthesize T. The findings and conclusions in this abstract have not been formally disseminated by NIOSH and should not be construed to represent any agency determination or policy.
Laboratory-animals; Animal-studies; Biodynamics; Fetus; Pregnancy; Prenatal-exposure; Chemical-reactions; Pesticide-residues; Pesticides-and-agricultural-chemicals
Agriculture, Forestry and Fishing; Manufacturing
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina