Gao X, Terranova P F, Rozman K K
Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Toxicol Appl Pharmacol. 2000 Mar 1;163(2):115-24. doi: 10.1006/taap.1999.8851.
Previous studies have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), and 1,2,3,4,7, 8-hexachlorodibenzo-p-dioxin (HxCDD), and their equipotent mixture block ovulation, reduce ovarian weight gain and alter preovulatory hormone levels in a similar manner. The objective of the current experiment was to investigate the effect of other structurally related compounds such as chlorinated furans and biphenyls on ovulation and related hormonal endpoints. The gonadotropin-primed immature female rat model was used to study the effect of 2,3,4,7, 8-pentachlorodibenzofuran (PeCDF), 3,3',4,4',5-pentachlorobiphenyl (PeCB), and 2,2',5,5' tetrachlorobiphenyl (TCB) and their mixture with polychlorinated dibenzo-p-dioxins (PCDDs) on ovulation. Rats were dosed on Day 23 of age at 0900 h with individual congeners (PeCDF, PeCB, TCB) or a mixture of five compounds, which included TCDD, PeCDD, HxCDD, in addition to PeCDF and PeCB. Equine choronic gonadotropin (eCG; 5 IU) was injected 24 h later to induce follicular development. Blood and ovaries were harvested, and ovarian weights determined at various times after eCG. Serum concentrations of 17beta-estradiol (E(2)), progesterone (P(4)), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were determined by radioimmunoassay. At 72 h after injection of eCG, the number of ova shed was measured by irrigating the ova from oviducts. The slopes of the dose-responses for inhibition of ovulation generated by the individual PeCDF, PeCB, and/or their mixture with PCDDs were similar. PeCDF, PeCB, and the mixture increased serum concentrations of E(2) at 72 h after eCG injection, the day of expected ovulation; in contrast, serum P(4) and FSH were decreased at that same time point. Only the high doses of TCDD, PeCDF, and PeCB blocked LH and FSH surges at 58 h after eCG. The ovarian histology revealed that the effects of PeCDF, PeCB, and the mixture were very similar to those of PCDDs, consisting of ova in large preovulatory follicles and a lack of or reduced number of corpora lutea. Parallel dose-responses of the individual congeners (PeCDF and PeCB) and their equipotent mixture with PCDDs support the toxic equivalency (TEQ) concept for the blockage of ovulation. Thus, PCDDs, PCDFs, and PeCBs appear to block ovulation by the same or a very similar mechanism of action.
先前的研究表明，2,3,7,8-四氯二苯并对二恶英（TCDD）、1,2,3,7,8-五氯二苯并对二恶英（PeCDD）、1,2,3,4,7,8-六氯二苯并对二恶英（HxCDD）及其等效混合物会以类似方式阻断排卵、减少卵巢重量增加并改变排卵前激素水平。当前实验的目的是研究其他结构相关化合物（如氯代呋喃和联苯）对排卵及相关激素指标的影响。使用促性腺激素预处理的未成熟雌性大鼠模型来研究2,3,4,7,8-五氯二苯并呋喃（PeCDF）、3,3',4,4',5-五氯联苯（PeCB）、2,2',5,5'-四氯联苯（TCB）及其与多氯二苯并对二恶英（PCDDs）的混合物对排卵的影响。在大鼠23日龄的09:00时，给它们分别注射各同系物（PeCDF、PeCB、TCB）或五种化合物的混合物，该混合物除了PeCDF和PeCB外，还包括TCDD、PeCDD、HxCDD。24小时后注射马绒毛膜促性腺激素（eCG；5国际单位）以诱导卵泡发育。在eCG注射后的不同时间采集血液和卵巢，并测定卵巢重量。通过放射免疫分析法测定血清中17β-雌二醇（E₂）、孕酮（P₄）、促黄体生成素（LH）和促卵泡生成素（FSH）的浓度。在注射eCG 72小时后，通过冲洗输卵管来测量排出的卵子数量。由单独的PeCDF、PeCB和/或它们与PCDDs的混合物产生的抑制排卵的剂量反应斜率相似。在预期排卵日，即eCG注射后72小时，PeCDF、PeCB和混合物会使血清E₂浓度升高；相反，在同一时间点血清P₄和FSH会降低。只有高剂量的TCDD、PeCDF和PeCB会在eCG注射后58小时阻断LH和FSH的峰值。卵巢组织学显示，PeCDF、PeCB和混合物的作用与PCDDs非常相似，表现为大的排卵前卵泡中有卵子，黄体数量缺乏或减少。各同系物（PeCDF和PeCB）及其与PCDDs的等效混合物的平行剂量反应支持了排卵阻断的毒性当量（TEQ）概念。因此，PCDDs、PCDFs和PeCBs似乎通过相同或非常相似的作用机制阻断排卵。
