Antagonistic activity towards the androgen receptor independent from natural sex hormones in human milk samples from the Norwegian HUMIS cohort
Antagonistic activity towards the androgen receptor independent from natural sex hormones in human milk samples from the Norwegian HUMIS cohort
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DOI：
10.1016/j.envint.2020.105948
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发表时间：
2020-10-01
影响因子：
11.8
通讯作者：
van der Burg, Bart
中科院分区：
文献类型：
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作者：
Collet, Berenice;van Vugt-Lussenburg, Barbara M. A.;van der Burg, Bart
在本文中，我们调查了可能存在的内分泌干扰物（EDCs）的基础上测量总雌激素和雄激素活性的母乳样品。我们使用特定的生物测定分析雌激素和雌激素样内分泌干扰物和雄激素和雄激素样内分泌干扰物的内分泌活性，并开发了一种分离方法，以评估从天然激素相比，内分泌干扰物的总内分泌活动的贡献。我们从挪威HUMIS人乳生物库中随机提取了10个样品，并使用ER α-和AR CALUX（R）生物测定法分析了它们的激动或拮抗活性。该研究显示，10份评估的人乳样品中有8份对雄激素受体具有拮抗活性，而10份样品中有2份对ER α具有激动活性。进一步的研究表明，10个样品中有9个极性部分具有抗雄激素活性，而非极性提取物均为阳性。使用合并极性浸提液，通过液相色谱分馏结合生物分析和涉及UHPLC-Q-TOF-MS/MS的非靶标筛选，研究了导致AR CALUX中测定的拮抗活性的罪魁祸首化学物质。分析表明，测得的抗雄激素生物活性不能解释内源性激素或其代谢产物的存在。我们已经证明，挪威母亲的母乳中含有抗雄激素活性，这很可能与人为极性内分泌干扰物的存在有关，而不受天然性激素的直接干扰。这些发现证明了对母乳中内分泌生物活性的更大规模调查，以及探索活性的化学来源及其对发育中婴儿健康的潜在影响。
In this paper, we investigated the possible presence of endocrine disrupting chemicals (EDCs) based on measuring the total estrogenic and androgenic activity in human milk samples. We used specific bioassays for analysis of the endocrine activity of estrogens and estrogen-like EDCs and androgens and androgen-like EDCs and developed a separation method to evaluate the contribution from natural hormones in comparison to that of EDCs to total endocrine activities. We extracted ten random samples originating from the Norwegian HUMIS biobank of human milk and analyzed their agonistic or antagonistic activity using the ER alpha- and AR CALUX (R) bioassays. The study showed antagonistic activity towards the androgen receptor in 8 out of 10 of the assessed human milk samples, while 2 out of 10 samples showed agonistic activity for the ER alpha. Further investigations demonstrated anti-androgenic activity in the polar fraction of 9 out of 10 samples while no apolar extracts scored positive. The culprit chemicals causing the measured antagonistic activity in AR CALUX was investigated through liquid chromatography fractionation coupled to bioanalysis and non-target screening involving UHPLC-Q-TOF-MS/MS, using a pooled polar extract. The analysis revealed that the measured anti-androgenic biological activity could not be explained by the presence of endogenous hormones nor their metabolites. We have demonstrated that human milk of Norwegian mothers contained anti-androgenic activity which is most likely associated with the presence of anthropogenic polar EDCs without direct interferences from natural sex hormones. These findings warrant a larger scale investigation into endocrine biological activity in human milk, as well as exploring the chemical sources of the activity and their potential effects on health of the developing infant.