The Expression Of TSHR On Ovary And Fas,NF-κB On Placenta In PTU-induced Thyroid Dysfunction In Rats And Their Relation With Adverse Pregnancy

BackgroundHypothyroidism is a common disease in pregnant women. Clinical work found that thyroid disorders affect the reproductive system, leading to female infertility, there occurs the case of abortion, stillbirth and other adverse pregnancy outcomes. Pregnancy is an allograft immune response,immunine environment in woman changes with pregnancy,the reproductive organs of the immune microenvironment is of great significance to occurrence and maintenance of pregnancy. Endocrine system includes the hypothalamus- pituitary- gonadal axis, the hypothalamus- pituitary- thyroid axis and hypothalamic- pituitary- adrenal axis, the hypothalamic- pituitary- thyroid axis and the interaction between gonadal axis has been endocrinology and gynecology production focus of scientific research, but on immune factors in the mechanism between the two were not yet clear. So study the possible mechanism of immune factors between the two affect each other for better prevention and improvement of clinical adverse pregnancy has important significance.ObjectiveIn this study,through the establishment of pregnancy and hypothyroid rat model, the detection of associated inflammatory cytokines, hormone and ovarian tissue TSHR and placental tissue expression of NF-κB, Fas to explore possible role of the immune system associated inflammatory cytokines and ovarian TSHR and placental NF-κB, Fas in adverse pregnancy outcomes caused by hypothyroidism.Methods106 female SD rats were randomly divided into two groups, the group which the rats were fed with normal water(n=30), and the experiment group(n=76) in which the rats were fed with 0.05% 6-n-propyl thiouracil(PTU) in drinking.After 6 weeks,5 rats of each group were randomly selected out to detect the thyroid hormones.If the experiment group were in hypothyroid state, then randomly selected 5 rats from normal water group as the control group(NG,n=5),5 rats as hypothyroid group(HG,n=5) randomly selected from the experiment group.After that, the remaining rats as hypothyroidism cage group(LHG,n=71) and normal cage group(LNG,n=25) were kept in cages with adult male rats for conception,if pregnancy,we ascribed them to the normal pregnancy group(NPG,n=10) and hypothyroid pregnancy group(HPG,n=28). The serum levels of T3, T4, TSH, TNF-α, IL-2, IL-6 and LH, FSH, P, E were measured through ELISA as well as the immunohistochemical expression of TSHR on the ovary and Fas,NF-κB on the placental disks.Results1the pregnancy rate of hypothyroidism cage group presented no statistical differences compared to normal cage group;the rate of abortion was higher in the hypothyroid pregnancy group compare to the normal pregnancy group(P<0.05);2The hypothyroid group had the higher TNF-α,IL-6 levels(P<0.01) compared to control group,no difference was found for IL-2 level(P >0.05).The hypothyroid group had the higher levels of LH,FSH(P<0.05) and lower E,P(P<0.05)compared to the control group;3The serum levels of both TNF-α and IL-2 were found to be similar(P >0.05), while the IL-6 was found to be higher in normal pregnancy group(P<0.05)when compared to control group;4Just IL-6 presented significant change(P<0.05)in the hypothyroid pregnancy group when compared to hypothyroid group;5The serum levels of TNF-α, IL-2 and IL-6 in hypothyroid pregnancy group were significantly higher than those in normal pregnancy group(P<0.05);6The expression of TSHR in primordial follicles,primary follicles and secondary follicles in hypothyroid group presented no statistical significance compare to control group while the level of TSHR in corpus luteum in hypothyroid group was higher than that in control group(P<0.05);7The expression of Fas and NF-κB in hypothyroid pregnancy group was higher than those in normal pregnancy group(P <0.05);8TNF-α and IL-6 in the hypothyroid group and control group had positive linear correlation with TSHR expressed in corpus luteum(P<0.05);9TNF-α, IL-2 and IL-6 in the hypothyroid pregnancy group and normal pregnancy group had positive linear correlation with Fas and NF-κB(P<0.01,P<0.05);Conclusion1Hypothyroidism changes the serum levels of cytokines like TNF-α,IL-2 and IL-6 correlated with the immune system in rats and its pregnancy state which is different from changes in normal pregnant rats,it indicates that hypothyroid changes the immune state in normal pregnancy may one of the mechanisms result in adverse pregnancy outcomes.2The high expression of TSHR on corpus luteum of ovary has relationship with TNF-α and IL-6,this maybe another road which hypothyroid correlation with the disfunction of reproduction organs and then lead to the adverse pregnancy outcomes.3Hypothyroid changes the serum levels of cytokines as well as improved the expression of the Fas,NF-κB in the placental disk demonstate that hypothyroid may lead to adverse pregnancy outcomes through changing the local immune of placenta.