The Research Of Hypothyroidism During Pregnancy Inducing Glucose And Lipid Dysregulation In Early Life Of Female Offspring

Objective The changes of thyroid hormone level during pregnancy will affect the intrauterine development of the fetus,and also have a certain regulatory effect on lipid and glucose metabolism.Previous researches mostly focus on the influence of hypothyroidism during pregnancy of pregnancy outcome and the neurodevelopment of offspring,while there are few studies on the effects of metabolism in early offspring.Therefore,the aim of this study was to assess the effects on thyroid function and glucose and lipid metabolism in the early life of female offspring by constructing a maternal hypothyroidism model during pregnancy,so as to provide new ideas for clinical treatment and drug development.Methods Female mice(C56BL/6J)were randomly divided into normal control group(NC0),hypothyroidism combined pregnancy group(PH0),pregnancy with hypothyroidism group(GH0).Firstly,the PH group was intervened with diet containing0.15% propylthiouracil(PTU)and normal drinking water for 28 days,while the NC0 group and GH0 group were given normal diet and water.Blood samples was collected from each group(n=6/group),and serum free thyroxine(FT4),free triiodothyronine(FT3)and thyroid-stimulating hormone(TSH)levels were measured to assess Whether the model is successful or not.Then the female mice and male mice in each group were caged in a 2:1 ratio.From the confirmation of the white vaginal plug to the end of delivery,the female mice in the GH0 and PH0 groups were given IDP diet and normal water.The NC0 group provided normal Diet and water.After delivery,the levels of FT3,FT4,and TSH in female mice of each group were tested to confirm whether GH0 and PH0 groups were in hypothyroidism at delivery.The female offspring of each group were divided into normal control group(NC1),hypothyroidism combined pregnancy group(PH1)and pregnancy with hypothyroidism group(GH1).After weaning(3 weeks of age),measurements of blood glucose and body weight and glucose tolerance tests were performed.Samples were taken after fasting for 8 h,After centrifugation,whole blood was taken to detect serum levels of FT3,FT4,TSH,Insulin and blood lipids.Thyroid,liver,and pancreas tissues were embedded in sections to observe pathological changes.and the protein expressions related to fatty acid and cholesterol metabolism were detected by Western Blotting.Results Compared with the NC1 group,the TSH level was increased and the levels of T4 and T3 were decreased in the GH1 and PH1 groups;The body weight of GH1 and PH1 groups was lower than the NC1 group,the blood glucose level was higher than that in the NC1 group and the fasting glucose tolerance was impaired,and the morphology of islet structure damage was reduced by hematoxylin-eosin staining(HE)of the pancreas;the serum TC,TG,and liver TG levels were increased in the GH1 and PH1 groups,and the phenomenon of lipid deposition in the liver of these two groups of offspring was found by HE staining.And the expression levels of lipid metabolism-related proteins: SREBP1 c,FAS,and CD36 in the liver increased,and the degree was more obvious in PH1;the expression of CPT1 A and LDL-R was down-regulated.In addition,the levels of HMGCR,a key enzyme in hepatic TC and cholesterol synthesis,were increased in both GH1 and PH1 groups compared with NC1.Conclusion Hypothyroidism during pregnancy in mice can lead to disorders of glucose and lipid metabolism in the early life of female offspring mice,liver lipid deposition,elevated blood lipids,impaired glucose tolerance,insulin resistance.While the thyroid,pancreas,and liver tissues are subjected to different degrees of pathological damage In addition,the female offspring of hypothyroidism during pregnancy have developmental retardation.The female offspring of hypothyroidism combined with pregnancy group are more likely to cause lipid metabolism disorder than the female offspring of pregnancy with hypothyroidism group.