Neonatal exposure to technical methoxychlor alters pregnancy outcome in female mice

This study was designed to determine the ability of female mice who were ex posed neonatally to the pesticide methoxychlor (MXC) to mate, ovulate, and become pregnant upon reaching sexual maturity. One-day-old female mice (5 t o 8/group) were exposed daily by intraperitoneal (ip) injection for 14 d to either sesame oil or 10 mu g estradiol-17 beta or 0.1, 0.5 or 1.0 mg MXC s uspended in sesame oil. The MXC exposures corresponded to 14 to 71, 68 to 3 57, or 135 to 714 mg/kg body weight, respectively, Three months later, fema le mice were placed with proven breeder males and checked daily for vaginal plugs. Mated female mice were sacrificed 18 d after the appearance of a va ginal plug to evaluate pregnancy. Uteri were examined for the presence of l iving fetuses and/or resorption sites. Ovaries were removed and prepared fo r histologic evaluation and tabulation of corpora lutea, All mice from all three MXC-treated groups did in fact mate, in comparison with only one of t hose exposed neonatally to estradiol, Increasing the dose of MXC produced a decreased number of pregnant animals at 18 d following mating. The mean nu mber of five fetuses/litter was reduced in the 0.5 and 1.0 mg MXC-treated g roups. Corpora lutea were significantly reduced in ovaries from only the 1. 0 mg MXC group and the estradiol group. No effects of treatment were seen a t 0.1 mg MXC, It is concluded that neonatal exposure to MXC does not interf ere with mating. Instead, significant alterations are seen in initiating an d/or maintaining pregnancy. The deleterious effects on pregnancy may be due to the influence of neonatal MXC treatments on the hypothalamic-pituitary- ovarian axis as well as on possible alteration of the uterine environment. (C) 1998 Elsevier Science Inc.