摘要
Background:Hypothyroxinemia is a subclinical thyroid hormone deficiency in which the mother has inadequate levels of T_(4) during pregnancy.The fetus relies entirely on the mother's T_(4) hormone level for early neurodevelopment.Isolated maternal hypothyroxinemia(IMH)in the first trimester of pregnancy can lead to lower intelligence,lower motor scores,and a higher risk of mental illness in descendants.Here,we focus on the autism-like behavior of IMH offspring.Methods:The animals were administered 1 ppm of propylthiouracil(PTU)for 9 weeks.Then,the concentrations of T_(3),T_(4),and thyroid-stimulating hormone(TSH)were detected using enzyme-linked immunosorbent assay(ELISA)to verify the developed animal model of IMH.We performed four behavioral experiments,including the marble burying test,open-field test,three-chamber sociability test,and Morris water maze,to explore the autistic-like behavior of 40-day-old offspring rats.Results:The ELISA test showed that the serum T_(3) and TSH concentrations in the model group were normal compared with the negative control group,whereas the T_(4) concentration decreased.In the behavioral experiments,the number of hidden marbles in the offspring of IMH increased significantly,the frequency of entering the central compartment decreased,and the social ratio decreased significantly.Conclusion:The animal model of IMH was developed by the administration of 1 ppm of PTU for 9 weeks,and there were autistic-like behavior changes such as anxiety,weakened social ability,and repeated stereotyping in the IMH offspring by 40 days.
基金
supported by the CAMS Innovation Fund for Medical Science (2021-I2M-1-034)
the National Natural Science Foundation of China (grant number:81700697).
