Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China.
J Trace Elem Med Biol. 2023 Sep;79:127267. doi: 10.1016/j.jtemb.2023.127267. Epub 2023 Jul 25.
We aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats.
Pregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system.
High iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = -0.909, p = 0.012; r = -0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = -0.917, p = 0.01; r = -0.859, p = 0.028; r = -0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = -0.990, p = 0.0002) and Txnrd2 expression (r = -0.979, p = 0.001; r = -0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased.
In addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.
我们旨在研究妊娠和哺乳期不同碘摄入量对母鼠和子鼠尿碘和血清碘浓度、脂肪酸代谢、甲状腺和心血管功能的影响。
将妊娠大鼠随机分为四组：正常成人碘摄入量（NAI，7.5μg/d）、正常孕妇碘摄入量（NPI，12.5μg/d）、高碘 5 倍组（5 HI，62.5μg/d）和高碘 10 倍组（10 HI，125μg/d）。母鼠持续给予碘化钾直至产后 16 天（PN16）。采用酶联免疫吸附试验（ELISA）测定甲状腺功能。采用电感耦合等离子体质谱法（ICP-MS）检测尿碘和血清碘浓度。采用实时定量聚合酶链反应（RT-qPCR）检测 Krüppel 样因子 9（KLF9）和硫氧还蛋白还原酶 2（Txnrd2）的信使核糖核酸（mRNA）表达。通过免疫组化和免疫荧光染色评估 KLF9 表达的特征分布及其与 TRβ 的相互作用。采用液相色谱-质谱法（LC-MS）分析血清脂肪酸。通过超声心动图和非侵入性尾套系统测量心功能和血压。
妊娠和哺乳期高碘摄入（5 HI 和 10 HI）导致母鼠和子鼠的尿碘浓度（UIC）、血清总碘浓度（STIC）和血清非蛋白结合碘浓度（SNBIC）均升高，同时血清游离三碘甲状腺原氨酸（FT3）及其靶基因 KLF9 的表达明显增加。在 5 HI 和 10 HI 组的母鼠中，收缩压（SBP）明显升高，升高的 SBP与升高的 UIC（r=0.968，p=0.002；r=0.844，p=0.035）、KLF9（r=0.935，p=0.006；r=0.954，p=0.003）和降低的 Txnrd2（r=-0.909，p=0.012；r=-0.912，p=0.011）呈显著正相关。在 10 HI 组的母鼠中，观察到心脏功能亢进，表现为左心室射血分数（LVEF）、左心室短轴缩短率（LVFS）增加，左心室舒张末期内径（LVESD）降低。升高的 LVEF 和降低的 LVESD与 UIC、STIC 和 SNBIC 呈显著正相关（r=0.976，p=0.001；r=0.945，p=0.005；r=0.953，p=0.003；r=-0.917，p=0.01；r=-0.859，p=0.028；r=-0.847，p=0.033），LVEF、LVFS 和 LVESD 与 KLF9（r=0.950，p=0.004；r=0.963，p=0.002；r=-0.990，p=0.0002）和 Txnrd2 表达（r=-0.979，p=0.001；r=-0.915，p=0.01；r=0.933，p=0.007）呈显著负相关，而降低的 LVESD 与降低的环氧二十碳三烯酸（EET）代谢物：5,6-EET、8,9-DHET 和 11,12-DHET 呈显著正相关（r=0.999，p=0.034；r=1.000，p=0.017；r=1.000，p=0.017）。然而，在子鼠中，SBP 和心功能没有明显变化。STIC 和 SNBIC 明显低于母鼠，二十碳五烯酸（EPA）代谢物（9-HEPE、15-HEPE 和 14,15-DiHETE）显著增加。
除了甲状腺激素外，STIC、SNBIC、KLF9、Txnrd2、EET 和 EPA 代谢物可能是高碘摄入诱导的甲状腺和心血管功能的有前途的生物标志物。
