Androgen disruption by dioxin exposure in 5-year-old Vietnamese children: Decrease in serum testosterone level

Androgen disruption by dioxin exposure in 5-year-old Vietnamese children: Decrease in serum testosterone level
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越南 5 岁儿童接触二恶英导致雄激素破坏:血清睾酮水平下降

DOI:
10.1016/j.scitotenv.2018.05.257
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发表时间:
2018
影响因子:
9.8
通讯作者:
NV Toan
NV Toan
中科院分区:
环境科学与生态学1区
文献类型:
--
作者:
NTP Oanh;T Kido;S Honma;Y Oyama;LT Anh; HD Phuc;NH Viet;HD Manh;R Okamoto;H Nakagawa;SF Nakayama;DD Nhu;DV Tung;VV Chi;NH Minh;NV Toan

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二恶英被怀疑是可能导致人体内分泌紊乱的物质。我们正在越南三个二恶英暴露地区(热点)之一进行研究。我们以前曾报道,唾液脱氢表雄酮(DHEA)水平下降,3岁的越南儿童,这是显着负相关的多氯二苯并二恶英/二苯并呋喃水平在他们的母亲的母乳。在这项研究中,我们调查了暴露于二恶英对类固醇激素生物合成的影响,在相同的儿童,当他们达到5岁,重点是雄激素。分别来自二恶英污染热点地区和非二恶英污染地区的35对和50对母子参与了这项研究。2008年,母亲在产后4至16周捐赠母乳,通过气相色谱/高分辨率质谱法测量二恶英水平。2013年从5岁儿童中收集血清。7甾体激素测定液相色谱/质谱。母乳中的大多数二恶英同系物在热点地区比非喷洒地区高2至10倍。DHEA和睾酮(T)在热点显着较低,并显示出负相关性,与大多数二恶英同系物。细胞色素P450-17、20裂解酶(CYP 17裂解酶)和17β-羟基类固醇脱氢酶(HSD)的活性也观察到类似结果。相反,热点地区儿童的雄烯二酮(A-二酮)水平和3β-HSD活性升高与二恶英水平呈正相关。T与17β-HSD呈正相关。二恶英可能抑制17β-HSD活性,导致T水平降低。多元回归分析表明,二恶英与DHEA,A-二酮和T水平有很强的关联。总之,本研究表明,二恶英与5岁儿童低水平的DHEA和T以及抑制类固醇生成酶如CYP 17裂解酶和17β-HSD的活性有关。
Dioxins have been suspected to be potential substances causing endocrine disruptions in humans. We are conducting the research in one of three dioxin exposure areas (hotspots) in Vietnam. We previously reported that the salivary dehydroepiandrosterone (DHEA) level decreased in 3-year-old Vietnamese children and that it was significantly inversely correlated with polychlorinated dibenzodioxin/dibenzofuran levels in their mother's breast milk. In this study, we investigated the influence of exposure to dioxin on steroid hormone biosynthesis in the same children when they reached 5 years of age, focusing on androgens. Thirty-five and 50 mother–child pairs from dioxin hotspot and non-sprayed areas, respectively, participated in this study. Maternal breast milk was donated at 4 to 16 weeks postpartum in 2008 to measure dioxin levels by gas chromatography/high-resolution mass spectrometry. Serum was collected from 5-year-old children in 2013. Seven steroid hormones were measured by liquid chromatography/mass spectrometry. Most dioxin congeners in breast milk were 2- to 10-fold higher in the hotspot than in the non-sprayed area. DHEA and testosterone (T) were significantly lower in the hotspot and showed negative correlations with most dioxin congeners. Similar results were observed for the activities of cytochrome P450-17, 20 lyase (CYP17 lyase), and 17β-hydroxysteroid dehydrogenase (HSD). Conversely, the elevated androstenedione (A-dione) level and 3β-HSD activity in children from the hotspot were positively correlated with dioxin levels. Moreover, a positive correlation was shown between T and 17β-HSD. It is possible that dioxin inhibits 17β-HSD activity, leading to a decrease in the T level. Multiple regression analysis indicated that dioxin had a strong association with the DHEA, A-dione, and T levels. In conclusion, the present study suggests that dioxin is associated with low levels of DHEA and T and inhibition of the activity of steroidogenic enzymes such as CYP17 lyase and 17β-HSD in 5-year-old children.