Augustowska K, Gregoraszczuk E E Łucja, Grochowalski A, Milewicz T, Mika M, Krzysiek J, Chrzaszcz R
Laboratory of Physiology and Toxicology of Reproduction, Department of Animal Physiology, Institute of Zoology, Jagiellonian University, Krakow, Poland.
Reproduction. 2003 Nov;126(5):681-7. doi: 10.1530/rep.0.1260681.
Explants of human placental tissue harvested immediately after expulsion were used to determine differences between accumulation of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated dibenzo-p-dioxin (PCDD)-polychlorinated dibenzo-p-furans (PCDF) environmental mixture, and their influence on placental steroidogenesis. Explants were cultured in vitro for 5 days in media supplemented each day with either TCDD or a mixture of PCDD-PCDF. Media were collected every day for steroid content analysis by radioimmunoassay. At 24 h after the last treatment, the tissue was frozen for further analysis of the content of TCDD or other congeners present in the mixture. Determinations of TCDD and all 17 PCDDs and PCDFs were performed using gas chromatography equipped with DB-5 MS and DB-17 capillary columns. In the control tissue, the amounts of both TCDD and mixture components were close to the limit of detection of the method. In the treated tissue, the TCDD accumulation was 94% of the total exposure to TCDD. The most toxic congeners 2,3,7,8-TCDD, 2,3,7,8-tetrachlorodibenzofuran, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (PeCDD), 1,2,3,7,8-pentachlorodibenzo-p-furans (PeCDF) and 2,3,4,7,8-PeCDF showed the highest accumulation, which covered >50% of the total toxic equivalents present in this mixture. During the first 3 days of exposure to TCDD there was no effect on the conversion of dehydroepiandrosterone to oestradiol, whereas on days 4 and 5 of exposure, a twofold decrease in oestradiol secretion was observed. However, a small but significant increase in oestradiol secretion was noted at all times of exposure to the PCDD-PCDF mixture. All observed changes in oestradiol secretion were not accompanied by changes in progesterone secretion after exposure to TCDD or the PCDD-PCDF mixture. In conclusion, a high accumulation of TCDD in the placental tissue resulted in a decrease in oestradiol secretion and in vivo this could result in a decrease in blood flow through the placenta. From the mixture, PeCDD and PeCDF in the higher amount accumulated in the placental tissue caused an increase in oestrogen secretion and as a consequence could activate oxytocin secretion from the pituitary and early pregnancy outcome.
在胎盘娩出后立即采集的人胎盘组织外植体，用于确定2,3,7,8-四氯二苯并对二恶英（TCDD）与多氯二苯并对二恶英（PCDD）-多氯二苯并呋喃（PCDF）环境混合物的蓄积差异，以及它们对胎盘类固醇生成的影响。外植体在体外培养5天，培养基每天补充TCDD或PCDD-PCDF混合物。每天收集培养基，通过放射免疫分析法分析类固醇含量。在最后一次处理后24小时，将组织冷冻，以进一步分析混合物中TCDD或其他同系物的含量。使用配备DB-5 MS和DB-17毛细管柱的气相色谱法测定TCDD以及所有17种PCDD和PCDF。在对照组织中，TCDD和混合物成分的量均接近该方法的检测限。在处理过的组织中，TCDD的蓄积量占TCDD总暴露量的94%。毒性最强的同系物2,3,7,8-TCDD、2,3,7,8-四氯二苯并呋喃、1,2,3,7,8-五氯二苯并对二恶英（PeCDD）、1,2,3,7,8-五氯二苯并对呋喃（PeCDF）和2,3,4,7,8-PeCDF显示出最高的蓄积量，占该混合物中总毒性当量的>50%。在暴露于TCDD后的前3天，对脱氢表雄酮向雌二醇的转化没有影响，而在暴露的第4天和第5天，观察到雌二醇分泌减少了两倍。然而，在暴露于PCDD-PCDF混合物的所有时间点，均观察到雌二醇分泌有小幅但显著的增加。在暴露于TCDD或PCDD-PCDF混合物后，所有观察到的雌二醇分泌变化均未伴有孕酮分泌的变化。总之，胎盘组织中TCDD的高蓄积导致雌二醇分泌减少，在体内这可能导致胎盘血流量减少。在混合物中，胎盘组织中蓄积量较高的PeCDD和PeCDF导致雌激素分泌增加，因此可能激活垂体的催产素分泌并影响早期妊娠结局。
