Ac. Bourque et al., ULTRASTRUCTURAL-CHANGES IN OVARIAN FOLLICLES OF MONKEYS ADMINISTERED HEXACHLOROBENZENE, American journal of veterinary research, 56(12), 1995, pp. 1673-1677
Objective - To test hexachlorobenzene (HCB), an environmental pollutan
t, for its potential toxicity to the ovary. Design - Nonhuman primates
were orally administered the pollutant at doses between 0.01 and 10 m
g of HCB/kg of body weight to test viability of ovarian follicles. At
the end of dosing period, the monkeys received a compound that contain
ed follicle-stimulating and luteinizing hormones to stimulate developm
ent of follicles that would be examined by electron microscopy. Animal
s - Twenty, 6- to 13-year-old cynomolgus monkeys were randomly assigne
d to 5 groups. Procedure - The HCB, in concentrations of 0.01, 0.1, 1.
0, and 10.0 mg/kg, was orally administered with glucose in gelatin cap
sules for 13 weeks. Monkeys receiving capsules containing glucose only
served as controls. After the 13th week, monkeys were given a compoun
d that contained follicle-stimulating and luteinizing hormones daily d
uring 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 lap
arotomy. Approximately 1-mm cubes of tissue from each ovary were harve
sted, fixed by immersion in buffered 2% glutaraldehyde, and processed
for transmission electron microscopy. Results - Ultrastructure of ovar
ian follicles was altered in the monkeys administered HCB. Lesions wer
e observed in the follicles from monkeys given the lowest concentratio
ns 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, a
nd appearance of abnormal spaces between follicular cells were observe
d 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. Mitoc
hondria were condensed, with abnormal intracristal spaces in the lower
-dosage groups, and were markedly degenerated in the 10 mg/kg group. T
he effects of HCB were dose-related. Conclusion - The HCB is a reprodu
ctive system toxicant, and its damaging effects may be a result of aug
mentation of lipid peroxidation, especially in the primary follicle, w
hich abnormally affects cellular membranes and thus, impairs their per
meability.