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毛发分析揭示了混合农药暴露对雌性大鼠激素谱的影响。

Hormonal profile changes induced by pesticide mixture exposure in female rats revealed by hair analysis.

机构信息

Human Biomonitoring Research Unit, Department of Precision Health, Luxembourg Institute of Health, 1 A-B rue Thomas Edison, 1445, Strassen, Luxembourg.

Toxalim (Research Center in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, 31300, Toulouse, France.

出版信息

Chemosphere. 2022 Sep;303(Pt 2):135059. doi: 10.1016/j.chemosphere.2022.135059. Epub 2022 May 26.

Abstract

Pesticide exposure has been associated with hormonal disruption in both animals and humans. However, there is limited knowledge of the combined effects of complex mixtures of pesticides on endogenous hormone levels. Here, we used hair analysis to assess the impact of a pesticide mixture comprising 19 components from multiple chemical classes at eight doses of 0-400 μg/kg body weight (bw) three times per week per component on concentrations of 36 steroid and thyroid hormones in female rats over a 90-day exposure period. We detected 13 hormones in rat hair, namely estradiol (E2), androstenedione (AD), testosterone (T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), pregnenolone (P5), progesterone (P4), 11-deoxycorticosterone (11-DOC), corticosterone (CORT), 3,3'-l-diiodothyronine (T2), 3,5,3'-l-triiodothyronine (T3), 3,3',5'-l-triiodothyronine (rT3), and 3,5,3',5'-l-tetraiodothyronine (T4). In comparison to the control group, hair E2 concentration was significantly lower in the two highest (200 and 400 μg/kg bw) exposure groups, whereas hair DHEAS and CORT concentrations were significantly higher in the 40 μg/kg bw and the highest exposure groups, respectively. Results from generalized additive models suggest that pesticide exposure resulted in monotonic dose responses in hair E2 concentration, CORT concentration and DHEA/CORT molar ratio but nonmonotonic dose responses in hair T concentration, DHEAS concentration, P4/P5 and DHEA/DHEAS molar ratios. The associations of E2, CORT and DHEA/CORT ratio with exposure intensity were confirmed by their significant linear relationships with hair concentrations of at least 23 of the 25 exposure biomarkers analyzed. Our results demonstrate that exposure to low levels of the pesticide mixture evaluated here can alter hair reproductive and adrenal hormones levels.

摘要

农药暴露已被证明会在动物和人类体内引起激素紊乱。然而,对于复杂农药混合物对内源性激素水平的综合影响,我们的了解还很有限。在这里,我们使用毛发分析来评估由来自多个化学类别的 19 种成分组成的农药混合物在每周三次、每次每个成分 0-400μg/kg 体重 (bw) 的 8 个剂量下对雌性大鼠 90 天暴露期内 36 种类固醇和甲状腺激素浓度的影响。我们在大鼠毛发中检测到 13 种激素,即雌二醇 (E2)、雄烯二酮 (AD)、睾酮 (T)、脱氢表雄酮 (DHEA)、脱氢表雄酮硫酸酯 (DHEAS)、孕烯醇酮 (P5)、孕酮 (P4)、11-脱氧皮质酮 (11-DOC)、皮质酮 (CORT)、3,3'-l-二碘甲状腺原氨酸 (T2)、3,5,3'-l-三碘甲状腺原氨酸 (T3)、3,3',5'-l-三碘甲状腺原氨酸 (rT3) 和 3,5,3',5'-l-四碘甲状腺原氨酸 (T4)。与对照组相比,在最高的两个暴露组 (200 和 400μg/kg bw) 中,毛发 E2 浓度显著降低,而在 40μg/kg bw 和最高暴露组中,毛发 DHEAS 和 CORT 浓度分别显著升高。广义加性模型的结果表明,农药暴露导致毛发 E2 浓度、CORT 浓度和 DHEA/CORT 摩尔比呈单调剂量反应,但毛发 T 浓度、DHEAS 浓度、P4/P5 和 DHEA/DHEAS 摩尔比呈非单调剂量反应。E2、CORT 和 DHEA/CORT 比值与暴露强度的相关性通过它们与至少 25 种分析的暴露生物标志物中的 23 种的毛发浓度的显著线性关系得到证实。我们的结果表明,暴露于所评估的低水平农药混合物会改变毛发生殖和肾上腺激素水平。

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