This study is designed to characterize the reproductive hazards that confront females engaged in occupations which subject them to potential exposure to pesticides. This study will provide a comprehensive assessment of the toxic effects of the estrogenic pesticide methoxychlor (MXC) on specific segments of the reproductive tract: the ovary, uterus and the oviduct. Exposure of the non-pregnant and pregnant female will provide the models to evaluate the relative risks of these individuals to impairments of morphological and physiological parameters of the reproductive tract. This study will examine functional outcomes such as effects on fertility and pregnancy and correlate these with the observed anatomic and metabolic alterations within the reproductive tract. Uteri of both pregnant and non-pregnant females will be evaluated at specific intervals following exposure to MXC. In addition, an evaluation of the effects of MXC exposure on newborns will also be evaluated and these data compared to the effects observed with adult exposure. Sexually mature virgin female mice were exposed to 0.1, 0.5, 1.0, 2.5 or 5.0 MXC via oral gavage for 5 consecutive days for four weeks. Controls received either sesame oil or 0.025 mg estradiol. At sacrifice, segments from each uterine horn were prepared for morphometric studies or for transmission electron microscopy. Results revealed a dose-dependent increase in the heights of uterine lining cells. The cell heights of the two groups treated with the highest doses of the pesticide were similar to that of the estradiol group. Electron microscopy revealed increased vacuolization and swelling of mitochondria in cells of the 2.5 and 5.0 mg treated groups when compared to either of the control groups. In addition, there were effects on the number and size of microvilli in the uterine epithelial cells. This segment of the study clearly demonstrates that a four week exposure of adult female mice to 50% MXC elicits significant estrogenic and toxic effects on the uterine epithelium. The ovulatory process is reduced and implantation is severely impeded making a normal pregnancy unlikely. It is interesting to note that once the MXC exposure ceases, the lining of the uterus returns to normal. In the second arm of the study, pregnant mice were exposed to 1.25, 2.5, 5.0 or 10.0 mg MXC on Days 5, 6 and 7 of pregnancy. Some of these animals were sacrificed on Day 8 at which time the uteri were removed and examined for the presence of developing embryos. Those animals exposed to the higher doses of MXC at these times aborted the embryos that were implanting. However, these females were able to become pregnant and successfully bring healthy fetuses to term within two months, if no further exposure to MXC occurred. Thus, exposure of a pregnant female early in pregnancy to MXC has a deleterious effect on that particular pregnancy, but, if the exposure is discontinued, future pregnancies are not at risk. The third segment of this study dealt with exposing newborn female mice to MXC and then comparing their reproductive activity upon reaching adulthood with that of the mice exposed as adults in the first two arms of this study. One-day old female mice were exposed to either 0.1, 0.5 or 1.0 mg MXC for fourteen consecutive days. By two months of age the ovaries of mice exposed to 0.5 and 1.0 mg MXC were smaller than controls, since there were few, if any, corpora lutea in the MXC-treated mice. This indicated that these mice were ovulating few, if any, eggs. These mice were able to mate, but there was a reduced number of pregnancies and a significant reduction in the number of live young. Thus, unlike exposure of either an adult nonpregnant female or a pregnant female where there is an immediate effect on reproductive activity followed by a complete reversal of this toxicity once exposure ceases, exposure of a newborn female causes a subsequent decrease in reproductive activity which may be permanent.
Louisiana State University, School of Medicine, Department of Anatomy, 1901 Perdido Street, New Orleans, LA 70112-1393
Louisiana State University, School of Medicine, Department of Anatomy, New Orleans, Louisiana