Section of Environmental Health, Department of Public Health, University of Copenhagen, Oester Farimagsgade 5A, 1353 Copenhagen K, Denmark.
Faculty of Food Science and Nutrition, School of Health Sciences, University of Iceland, Hjarðarhagi 2-6, 107 Reykjavík, Iceland; Maternal Nutrition Group, Department of Epidemiology, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark.
Environ Int. 2010 May;36(4):344-351. doi: 10.1016/j.envint.2010.02.002. Epub 2010 Feb 26.
In utero exposure to environmental dioxin-like, estrogen and androgen compounds can cause adverse health effects. Little is known about potential interactions in vivo between dioxin-like compounds, estrogens and androgens during fetal development in humans. Therefore we explored the potential interactions in vivo between dioxin-like compounds, estrogens, androgens using chemical-activated luciferase expression (CALUX)(R) bioassays in maternal and umbilical cord blood plasma concurrently collected at the time of planned Caesarean section from 98 healthy pregnancies. The dioxin-like activity was also determined after placental transfer of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the ex vivo human placenta perfusion system. Similar dioxin-like activity in maternal and cord blood (37 versus 33pg CALUX(R)-TEQ/g plasma lipids, P>0.05) was detected and it demonstrates transplacental transfer. Increased dioxin-like activity in the perfused placenta tissue after ex vivo TCDD perfusions (from 17 to 280pg CALUX(R)-TEQ/g plasma lipids) suggest that accumulation in the placenta prevents immediate transplacental transfer of TCDD. Androgenic activity were also similar in the paired mother-newborns (0.10 versus 0.18ng CALUX(R)-AEQ/mL plasma), whereas cord blood plasma estrogenic activity was higher than maternal levels (22.6 versus 18.5ng CALUX(R)-EEQ/mL plasma). In cord blood plasma androgenic activity was strongly positively associated with maternal levels (Rs=0.8, P<0.001) whereas dioxin-like and estrogenic activities were modestly associated with maternal levels (Rs</=0.4, P<0.001). The micronuclei frequency, an indicator of genetic instability was significantly associated with dioxin-like activity in cord blood, independently of other recorded factors (Rs=0.4, P<0.003). This study demonstrated interactions in vivo between dioxin-like, estrogenic and androgenic exposures during fetal development of humans.
子宫内暴露于环境中二恶英类、雌激素和雄激素化合物会导致不良健康影响。在人类胎儿发育过程中，关于二恶英类化合物、雌激素和雄激素之间潜在的体内相互作用知之甚少。因此，我们使用化学激活荧光素酶表达（CALUX）（R）生物测定法，同时检测了 98 例健康妊娠计划剖宫产时采集的母体和脐带血血浆中的二恶英类化合物、雌激素和雄激素的潜在体内相互作用。还在离体人胎盘灌注系统中研究了 2,3,7,8-四氯二苯并对二恶英（TCDD）胎盘转移后的二恶英样活性。在母血和脐血中检测到相似的二恶英样活性（37 与 33pg CALUX（R）-TEQ/g 血浆脂质，P>0.05），表明存在胎盘转移。离体 TCDD 灌注后灌注胎盘组织中二恶英样活性增加（从 17 增加至 280pg CALUX（R）-TEQ/g 血浆脂质），表明在胎盘内的蓄积阻止了 TCDD 的即刻胎盘转移。配对母婴的雄激素活性也相似（0.10 与 0.18ng CALUX（R）-AEQ/mL 血浆），而脐血血浆雌激素活性高于母体水平（22.6 与 18.5ng CALUX（R）-EEQ/mL 血浆）。在脐血血浆中，雄激素活性与母体水平呈强正相关（Rs=0.8，P<0.001），而二恶英样和雌激素活性与母体水平呈适度相关（Rs</=0.4，P<0.001）。微核频率，遗传不稳定性的指标，与脐血中二恶英样活性显著相关，与记录的其他因素无关（Rs=0.4，P<0.003）。这项研究表明，在人类胎儿发育过程中，二恶英类、雌激素和雄激素之间存在体内相互作用。
