Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats |
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| Institution: | 1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China;2. Department of Nutrition and Food Hygiene, School of Public Health, Tianjin Medical University, Tianjin 300070, China;3. Tianjin Key Laboratory of Ionic-Molecular of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, the Second Hospital of Tianjin Medical University, Tianjin 300211, China;1. Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, PR China;2. Department of Clinical Laboratory, Binzhou Medical University Hospital, Binzhou 256603, PR China;3. National Center for Orthopaedics, Department of Molecular Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Beijing 100035, PR China;4. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, PR China;5. College of Veterinary Medicine, China Agricultural University, Beijing 100083, PR China;6. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medicine Sciences & School of Basic Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100005, PR China;1. Applied and Environmental Physiology Unit, Department of Physiology, University of Ibadan, Nigeria;2. Department of Human Physiology, College of Health Sciences, Nnamdi Azikiwe University, Nnewi Campus, Nigeria;1. Department of Obstetrics and Gynaecology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpa?a, Avc?lar, Istanbul, Türkiye;2. Department of Internal Medicine, Faculty of Veterinary Medicine, Istanbul University-Cerrahpa?a, Avc?lar, Istanbul, Türkiye;3. Department of Biophysics, Faculty of Medicine, Beykent University, Büyükçekmece, Istanbul, Türkiye;4. Department of Biophysics, Cerrahpa?a Faculty of Medicine, Istanbul University-Cerrahpa?a, Fatih, Istanbul, Türkiye;5. Department of Pathology, Faculty of Veterinary Medicine, Istanbul University-Cerrahpa?a, Büyükçemece, Istanbul, Türkiye;6. Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul, Türkiye;1. Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China;2. National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China |
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| Abstract: | ObjectiveWe 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.MethodsPregnant 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.ResultsHigh 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.ConclusionIn 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. |
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| Keywords: | Thyroid hormones (TH) Cardiovascular function Maternal Offspring Iodide intake Serum total iodine concentration (STIC) Serum non-protein-bound iodine concentration (SNBIC) Epoxyeicosatrienoic acids (EETs) Eicosapentaenoic acids (EPAs) |
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