Zinc influences on brain development, pituitary an thyroidfunction iniodine-deficient pregnant and neonatal rats

Xiaoxia Yang; Jianchao Bian; Xin Wang; Haiming Wang; Yongping Liu; Shuzhen Wang; Zhichun Mu; Xinluan Li

摘要：BACKGROUND: Zinc (Zn) has been shown to greatly influence brain development. Zn supplements may reduce injury to cell membranes of the thyroid gland due to iodine deficiency. OBJECTIVE: To establish an iodine deficiency rat model using low-iodine food, which was supplemented with compound Zn and Zn gluconate, to observe the effects of Zn on brain development, as well as pituitary gland and thyroid gland function in iodine-deficient rats. DESIGN, TIME AND SETTING: Randomized grouping study of neural development was performed in the central laboratory of Shandong Institute for Prevention and Treatment of Endemic Disease from 1998 to 1999. MATERIALS: A total of 270 Wistar, female rats, one month after weaning, were used in this study, including 150 pregnant and 120 neonatal rats. Rats were randomly divided into six groups: normal control, model, iodine, compound Zn, iodine and compound Zn, and zinc gluconate. Each group contained 25 pregnant rats and 20 nenoatal rats. METHODS: The pregnant rats and 20 neonatal rats, and well as the normal group, were fed standard chow and allowed free access to tap water (containing 5 μ g/L iodine and 1 mg/L Zn). The remaining five groups were fed low-iodine chow. However, the model group received distilled water, the iodine group received potassium-iodide distilled water (containing 300 μ g/L iodine), the compound Zn group received distilled water and intragastrically administrated 10 mL/kg compound Zn solution, once per day, the iodine and compound Zn group received distilled water with 300 p g/L iodine and intragastrically administrated 10 mL/kg compound Zn solution, once per day. All treatments lasted 90 days. MAIN OUTCOME MEASURES: All pregnant rats were sacrificed on the day 21 of pregnancy. Body mass, number and rate of fetal absorption, as well as fetal death and malformation, were determined. Thyroid and pituitary gland weights were measured, as well as serum levels of thyroid hormone, gonadotropin, and sex hormones. In the experimental study of neonatal rats, the animals normally gave birth at day 21. At day 45 after birth of the neonatal rats, thyroid and pituitary gland weights were measured, and protein, DNA, and RNA concentrations were measured. RESULTS: Pregnant rats in the iodine group exhibited decreased urine iodine and body mass (F= 7.37, P < 0.01 ), increased thyroid absolute and relative weight (F= 7.01, 50.27, P < 0.01 ), as well as decreased T<,4> and FT<,4> (F = 7.01, 29.32, P < 0.01 ) and increased T<,3> and FT3 (F = 41.20, 5.94, P < 0.01 ). Gonadotrupic and sexual liorrnones were abnormal. The pregnant rats displayed decreased weight gain, and the rates of malformation, dead, and absorbed fetuses were increased. Compared with the control group, the neonatal rats with iodine deficiency exhibited lower brain weights (P < 0.01 ). Brain protein, DNA, and RNA, concentrations were decreased, with a rate of RNA/DNA (F = 5.70, 55.86, 25.65, 5.44, P < 0.01 ). Body mass was gradually increased (F= 6.74, P< 0.01), and the thyroid glands were enlarged (F= 50.01, 76.13, P< 0.01). Following Zn administration, thyroid gland weight was decreased in pregnant rats (P < 0.01 ). Thyroid hormone, gonadotropic hormones, and sexual hormones were restored to some degree. Fetal weight was increased, and the rates of malformation, dead, and absorbed fetuses were decreased. At the same time, neonatal rats gained body weight, displayed decreased thyroid gland weight, as well as increased protein, DNA, and RNA concentrations in the brain. The ratio of RNA/DNA and protein/DNA increased following Zn administration (P < 0.01 ). CONCLUSION: Zn supplementation may decrease the degree of goiter, ameliorate thyroid hormone disorder, as well as gonadotropic and sexual hormone disorders, and increase protein, DNA, and RNA content. Zn supplementation antagonized reproductive abnormalities in pregnant rats, decreased fetal growth,