Krüger Tanja, Hjelmborg Philip S, Jönsson Bo A G, Hagmar Lars, Giwercman Aleksander, Manicardi Gian-Carlo, Bizzaro Davide, Spanò Marcello, Rignell-Hydbom Anna, Pedersen Henning S, Toft Gunnar, Bonde Jens Peter, Bonefeld-Jørgensen Eva C
Department of Environmental and Occupational Medicine, Institute of Public Health, University of Aarhus, Aarhus, Denmark.
Environ Health Perspect. 2007 Dec;115 Suppl 1(Suppl 1):21-7. doi: 10.1289/ehp.9353.
Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE).
We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.
The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p'-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p'-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.
The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.
动物和体外研究表明,持久性有机污染物(POPs)干扰雄激素受体(AR)信号传导可导致人类男性生殖障碍。本研究的目的是比较不同POP暴露水平的研究组之间的血清外源性雄激素活性,并评估其与POP替代标志物2,2',4,4',5,5'-六氯联苯(CB-153)和1,1-二氯-2,2-双(对氯苯基)乙烯(p,p'-DDE)的相关性。
我们测定了血清中含有亲脂性POPs但不含内源性激素部分的外源性雄激素活性。分析了来自格陵兰、瑞典、华沙(波兰)和哈尔科夫(乌克兰)的成年男性血清(n = 261)。外源性雄激素活性通过单独血清提取物(XAR)以及在合成AR激动剂R1881存在下(XARcomp)对AR反式激活荧光素酶活性的影响来确定。
各研究组在XARcomp活性方面存在显著差异,因纽特人的该活性升高,而欧洲研究组则降低;我们未观察到XAR活性有差异。我们发现哈尔科夫的AR拮抗剂p,p'-DDE水平最高,相应地,该研究组中XARcomp活性降低的血清样本百分比最高。此外,欧洲研究组中XARcomp活性降低的血清样本百分比与p,p'-DDE血清水平一致。未发现血清XAR或XARcomp活性与两种POP标志物之间存在相关性。
研究组之间XARcomp血清活性的差异表明化学暴露情况、遗传和/或生活方式因素存在差异。