Regulation Of Thyroxine And Potassium Iodide On Human In Vitro Decidualization

Embryo implantation and decidualization are crucial for early pregnancy.Thyroid hormone(Thyroxine),a derivative of amino acid,is synthesized and secreted by thyroid gland.There are two kinds of thyroid hormones,including active T3 and precursor T4.Thyroxine is one of the most important hormones in humans and animals and mainly participates in energy metabolism and promotes growth and development.Thyroxine has different pathways of action,including genomic pathway in which T3 binds to thyroxine receptors.It also binds to the membrane receptor integrin?3 and activates the non-genomic signaling pathway of ERK1/2.Thyroid gland is closely related to reproduction.Abnormal thyroid function can change the endocrine and immune environment in women,resulting in the reduction of fertility.The women with clinical hypothyroidism will cause the metabolic disorder of sexual hormones in the body,resulting in ovarian dysfunction and the impact of early pregnancy.KI is one of the key elements for the synthesis of thyroxine.There are many molecules related to the synthesis and metabolism of thyroxine expressed in endometrium,which may also be one of the sites of thyroxine synthesis.However,it is not clear whether there is thyroxine synthesis in the endommetrium and how thyroxine synthesis is affected by KI.The effects of thyroxine on embryo implantation and decidualization remain to be explored.Human endometrial cell line 4003 cells were treated with T3 and T4.The results showed that T3 had no obvious effects on decidualization.Under in vitro decidualization,decidualization was significantly promoted by T4.The relative levels of membrane protein integrin?3,ERK1/2 and STAT3 were up-regulated significantly by T4.The ERK1/2inhibitor U0126 or STAT3 inhibitor abrogates the stimulatory effects of T4 on these molecules,suggesting that T4 regulates the decidualization process mainly through the non-genomic pathway.By immunofluorescence and galactosidase staining,we showed that T4 inhibits cell proliferation,promotes DNA damage,and accelerates acute aging.After human endometrial cell line 4003 cells were treated with KI for 1 h or 3 h,thyroid peroxidase(TPO)and thyroid transporter(TTR)were significantly increased.KI also causes a significant increase in the sodium iodine symporter NIS(SLC5A5)which is associated with I~-transport.Within a certain concentration range,KI can significantly up-regulate decidualization-related genes in a concentration-dependent manner.Similar to T4,KI may also promote decidualization through the non-genomic pathways.In conclusion,T4 mainly stimulates decidualization through the non-genomic pathway and the endometrium may be one site of thyroxine synthesis.