Instituto De Bioingeniería, Universidad Miguel Hernández De Elche, Elche, Alicante, Spain.
Institute of Food Chemistry and Food Biotechnology, Justus Liebig University Giessen, Giessen, Germany.
Reprod Toxicol. 2021 Apr;101:33-49. doi: 10.1016/j.reprotox.2021.02.004. Epub 2021 Feb 16.
Young adult wild-type and aryl hydrocarbon receptor knockout (AHRKO) mice of both sexes and the C57BL/6J background were exposed to 10 weekly oral doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; total dose of 200 μg/kg bw) to further characterize the observed impacts of AHR as well as TCDD on the retinoid system. Unexposed AHRKO mice harboured heavier kidneys, lighter livers and lower serum all-trans retinoic acid (ATRA) and retinol (REOH) concentrations than wild-type mice. Results from the present study also point to a role for the murine AHR in the control of circulating REOH and ATRA concentrations. In wild-type mice, TCDD elevated liver weight and reduced thymus weight, and drastically reduced the hepatic concentrations of 9-cis-4-oxo-13,14-dihydro-retinoic acid (CORA) and retinyl palmitate (REPA). In female wild-type mice, TCDD increased the hepatic concentration of ATRA as well as the renal and circulating REOH concentrations. Renal CORA concentrations were substantially diminished in wild-type male mice exclusively following TCDD-exposure, with a similar tendency in serum. In contrast, TCDD did not affect any of these toxicity or retinoid system parameters in AHRKO mice. Finally, a distinct sex difference occurred in kidney concentrations of all the analysed retinoid forms. Together, these results strengthen the evidence of a mandatory role of AHR in TCDD-induced retinoid disruption, and suggest that the previously reported accumulation of several retinoid forms in the liver of AHRKO mice is a line-specific phenomenon. Our data further support participation of AHR in the control of liver and kidney development in mice.
年轻成年野生型和芳香烃受体敲除（AHRKO）小鼠（雌雄两性）和 C57BL/6J 背景被暴露于每周 10 次口服 2,3,7,8-四氯二苯并对二恶英（TCDD；总剂量 200μg/kg bw），以进一步描述 AHR 以及 TCDD 对类视黄醇系统的观察到的影响。未暴露的 AHRKO 小鼠的肾脏比野生型小鼠重，肝脏比野生型小鼠轻，血清全反式视黄酸（ATRA）和视黄醇（REOH）浓度也比野生型小鼠低。本研究的结果还表明，鼠 AHR 在控制循环 REOH 和 ATRA 浓度方面发挥作用。在野生型小鼠中，TCDD 增加了肝脏重量并降低了胸腺重量，并大大降低了肝组织中 9-顺式-4-氧-13,14-二氢视黄酸（CORA）和视黄醇棕榈酸酯（REPA）的浓度。在雌性野生型小鼠中，TCDD 增加了肝组织中 ATRA 以及肾脏和循环 REOH 浓度。仅在雄性野生型小鼠中，TCDD 暴露后肾脏 CORA 浓度显著降低，血清中也有类似的趋势。相比之下，TCDD 对 AHRKO 小鼠没有影响。最后，在所有分析的类视黄醇形式的肾脏浓度中出现了明显的性别差异。总的来说，这些结果加强了 AHR 在 TCDD 诱导的类视黄醇紊乱中的强制性作用的证据，并表明以前报道的 AHRKO 小鼠肝脏中几种类视黄醇形式的积累是一种特定于系谱的现象。我们的数据进一步支持 AHR 参与控制小鼠肝脏和肾脏发育。
