Bourque A C, Singh A, Lakhanpal N, McMahon A, Foster W G
Department of Anatomy and Physiology, Atlantic Veterinary College, Charlottetown, Prince Edward Island, Canada.
Am J Vet Res. 1995 Dec;56(12):1673-7.
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.
测试环境污染物六氯苯（HCB）对卵巢的潜在毒性。
给非人灵长类动物口服剂量为0.01至10毫克HCB/千克体重的该污染物，以测试卵巢卵泡的活力。在给药期结束时，给猴子注射一种含有促卵泡激素和促黄体生成素的化合物，以刺激卵泡发育，之后通过电子显微镜进行检查。
20只6至13岁的食蟹猴被随机分为5组。
将浓度为0.01、0.1、1.0和10.0毫克/千克的HCB与葡萄糖装入明胶胶囊中口服，持续13周。仅接受含葡萄糖胶囊的猴子作为对照。在第13周后，从月经开始的第2至7天，每天给猴子注射一种含有促卵泡激素和促黄体生成素的化合物。在月经周期的第8天，注射5000国际单位的人绒毛膜促性腺激素，35至38小时后，通过剖腹术获取每只猴子的1个卵巢。从每个卵巢中采集约1立方毫米的组织块，浸入2%缓冲戊二醛中固定，然后进行透射电子显微镜处理。
给予HCB的猴子卵巢卵泡超微结构发生改变。在给予最低浓度HCB的猴子的卵泡中观察到病变，包括发育中的卵子和卵泡细胞中的线粒体凝聚，卵泡细胞核有深陷痕，细胞质脂滴异常积聚。在0.1至1.0毫克HCB/千克剂量组猴子的卵泡中观察到诸如卵质疝、卵泡细胞退化以及卵泡细胞间出现异常间隙等改变。最相关的改变出现在线粒体，这一细胞器似乎对该化合物最为敏感。在低剂量组中线粒体凝聚，嵴内间隙异常，在10毫克/千克组中线粒体明显退化。HCB的作用与剂量相关。
HCB是一种生殖系统毒物，其损害作用可能是脂质过氧化增强的结果，尤其是在初级卵泡中，这会异常影响细胞膜，进而损害其通透性。
