In utero and lactational exposure of Long-Evans rats to ammonium perchlorate (AP) disrupts ovarian follicle maturation

Abstract

Ammonium perchlorate (AP) is a powerful oxidizer manufactured almost exclusively for the aerospace industry. AP salts are also used in airbags, flares, fertilizers, enamels and paints. As a result of widespread industrial use, AP has become a persistent environmental contaminant of drinking water in several U.S. states. AP ion disrupts the trapping of iodide as well as facilitates the discharge of unorganified iodide from the thyroid gland. Such disturbances in thyroid hormone concentrations during critical periods of development are then known to cause profound reproductive and developmental defects, since thyroid hormones modulate both follicular development and steroidogenesis and affect estrogen metabolism and receptor. This study was designed (1) to determine whether exposure to a low or high concentration of AP (LAP, HAP) exerts detrimental effects on follicle maturation in the Long-Evans hooded rat and (2) to determine whether the modulatory effects of AP can be ameliorated by levo-thyroxine sodium (T 4) supplementation. Animals were treated via deionized drinking water on GD 7–21 with LAP (0.4 mg/kg/day) or HAP (4.0 mg/kg/day). Half of each group was also given T 4 supplements via drinking water on GD 7–21. Female pups were sacrificed on postnatal days 24/25, and the ovaries were excised, fixed for histology and analyzed. The analysis included a count, measurement and classification of preantral and antral follicles in the greatest cross-sectional area of the ovary. The results indicated that treatment with the HAP significantly reduced the number of preantral follicles <50,000 μm 2 and the total number of antral follicles in the <50,000, 50–100,000 and >100,000 μm 2 size classes. In ovaries treated with the LAP, we observed no significant decrease in preantral follicles of any size class and only a significant reduction in the largest antral follicles. T 4 only circumvented the effect on the number of small preantral and antral follicles; however, a significant diminution in the antral follicle number persisted in the mid-sized (HAP) and large (LAP, HAP)-sized classes. These data support the hypothesis that AP reduces the number of preantral and antral follicles in certain size classes in rats exposed during a critical period of development, and that T 4 can attenuate the effects of AP on small preantral and antral follicles, but not on medium or large antral follicles. (T35ES007292 & ES08342.)