Modulation of ovarian follicle maturation in Long-Evans rats exposed to polychlorinated biphenyls (PCBs) in-utero and lactationally

Polychlorinated biphenyls (PCBs) are ubiquitous man-made toxicants capable of endocrine disruption. Studies in several species have shown that exposure to PCBs and their hydroxylated metabolites reduces fecundity and decreases circulating concentrations of thyroid hormones, causing serious reproductive and developmental defects. Thyroid hormones modulate both follicular development and steroidogenesis, and affect estrogen metabolism and the regulation of estrogen receptor. This study was designed (1) to determine whether exposure to a commercially prepared PCB mixture (Aroclor 1016) exerts detrimental effects on follicle maturation in the Long-Evans hooded rat; and (2) to determine whether the modulatory effects of Aroclor can be attenuated by levo-thyroxine sodium (T-4) supplementation. Animals were treated on gestation days 7-13 with a single daily intraperitoneal injection (2.5 mg/kg per day) of Aroclor. Half of the Aroclor-treated dams were also given T-4 supplements (2.89 mug/kg per day) via drinking water. 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 healthy and atretic preantral and antral follicles in the greatest cross-sectional area. The results indicated that treatment with Aroclor significantly reduced the number of preantral follicles <50,000 mum(2) and the total number of antral follicles in the 50-100,000 and >100,000 mum(2) size classes. T-4 circumvented the Aroclor effect on the number of preantral follicles <50,000 mum(2); however, a significant reduction in the antral follicle number persisted in the 50-100,000 and >100,000 mum(2) size classes. In addition, we observed a significant increase in atresia in the Aroclor-treated ovaries in the antral <50,000 mum(2) size class, which was not present in ovaries exposed to both Aroclor and T-4. These data support the hypothesis that Aroclor reduces the number of preantral and antral follicles of certain size classes in rats exposed during the critical period of development, and that supplementation with T-4 can attenuate the effects of Aroclor on small, but not medium or large antral follicles. Atresia of small, antral follicles may constitute one of the underlying mechanisms by which folliculogenesis is modulated by Aroclor 1016. (C) 2003 Elsevier Inc. All rights reserved.