Ultrastructural changes in ovarian follicles of monkeys administered hexachlorobenzene

To test hexachlorobenzene (HCB), an environmental pollutant, for its potential toxicity to the ovary.

Nonhuman primates were orally administered the pollutant at doses between 0.01 and 10 mg of HCB/kg of body weight to test viability of ovarian follicles. At the end of dosing period, the monkeys received a compound that contained follicle-stimulating and luteinizing hormones to stimulate development of follicles that would be examined by electron microscopy.

Twenty, 6- to 13-year-old cynomolgus monkeys were randomly assigned to 5 groups.

The HCB, in concentrations of 0.01, 0.1, 1.0, and 10.0 mg/kg, was orally administered with glucose in gelatin capsules for 13 weeks. Monkeys receiving capsules containing glucose only served as controls. After the 13th week, monkeys were given a compound that contained follicle-stimulating and luteinizing hormones daily during days 2 to 7 from the start of menses. On day 8 of the menstrual cycle, 5,000 IU of human chorionic gonadotropin was administered, and 35 to 38 hours later, 1 ovary from each monkey was obtained during laparotomy. Approximately 1-mm cubes of tissue from each ovary were harvested, fixed by immersion in buffered 2% glutaraldehyde, and processed for transmission electron microscopy.

Ultrastructure of ovarian follicles was altered in the monkeys administered HCB. Lesions were observed in the follicles from monkeys given the lowest concentrations of HCB, and comprised condensed mitochondria in the developing ova and follicular cells that contained nuclei with deep indentations and abnormal accumulation of cytoplasmic lipid droplets. Alterations, such as herniation of the ooplasm, degeneration of the follicular cells, and appearance of abnormal spaces between follicular cells were observed in the follicles from monkeys of the 0.1 to 1.0 mg of HCB/kg dosage groups. The most relevant alterations were seen in the mitochondrion, an organelle that appeared to be most sensitive to the compound. Mitochondria were condensed, with abnormal intracristal spaces in the lower-dosage groups, and were markedly degenerated in the 10 mg/kg group. The effect of HCB were dose-related.

The HCB is a reproductive system toxicant, and its damaging effects may be a result of augmentation of lipid peroxidation, especially in the primary follicle, which abnormally affects cellular membranes and thus, impairs their permeability.