Thyroid Hormone Facilitates in vitro Decidualization of Human Endometrial Stromal Cells via Thyroid Hormone Receptors
Thyroid Hormone Facilitates in vitro Decidualization of Human Endometrial Stromal Cells via Thyroid Hormone Receptors
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DOI：
10.1210/endocr/bqaa049
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发表时间：
2020-06-01
期刊：
影响因子：
4.8
通讯作者：
Okada, Hidetaka
中科院分区：
文献类型：
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作者：
Kakita-Kobayashi, Maiko;Murata, Hiromi;Okada, Hidetaka
子宫内膜基质细胞通过蜕膜化过程分化为蜕膜细胞。这种分化对于胚胎植入和成功建立妊娠至关重要。最近的流行病学研究表明，甲状腺激素在着床期间对子宫内膜很重要，人们普遍认为甲状腺激素对于正常发育、分化、生长和代谢至关重要。本研究旨在探讨甲状腺激素对人子宫内膜间质细胞（hESCs）蜕膜化的影响，并通过基因打靶的方法确定其在体外的生理作用。为了确定甲状腺激素的表达模式，我们进行了基因表达谱的人胚胎干细胞在蜕膜化后，他们与甲状腺激素左旋甲状腺素（LT4）治疗。在卵巢类固醇激素和甲状腺激素联合治疗后，观察到蜕膜反应显著增加。此外，LT4处理也影响了许多重要的蜕膜化转录因子的调节。我们发现，3型脱碘酶，这是特别重要的胎儿和胎盘组织，在蜕膜化过程中，在甲状腺激素的存在上调。此外，还观察到孕酮受体，一种卵巢类固醇激素受体，参与甲状腺激素诱导的蜕膜化。在缺乏甲状腺激素受体（TR）的情况下，由于TRa和TR β的同时沉默，在蜕膜化过程中甲状腺激素的表达没有变化。总之，我们证明了甲状腺激素对子宫内膜的蜕膜化是必不可少的。这是首次在体外研究中发现蜕膜化受损是亚临床甲状腺功能减退症（SCH）患者不孕的可能原因。
Endometrial stromal cells differentiate into decidual cells through the process of decidualization. This differentiation is critical for embryo implantation and the successful establishment of pregnancy. Recent epidemiological studies have suggested that thyroid hormone is important in the endometrium during implantation, and it is commonly believed that thyroid hormone is essential for proper development, differentiation, growth, and metabolism. This study aimed to investigate the impact of thyroid hormone on decidualization in human endometrial stromal cells (hESCs) and define its physiological roles in vitro by gene targeting. To identify the expression patterns of thyroid hormone, we performed gene expression profiling of hESCs during decidualization after treating them with the thyroid hormone levothyroxine (LT4). A major increase in decidual response was observed after combined treatment with ovarian steroid hormones and thyroid hormone. Moreover, LT4 treatment also affected the regulation of many transcription factors important for decidualization. We found that type 3 deiodinase, which is particularly important in fetal and placental tissues, was upregulated during decidualization in the presence of thyroid hormone. Further, it was observed that progesterone receptor, an ovarian steroid hormone receptor, was involved in thyroid hormone-induced decidualization. In the absence of thyroid hormone receptor (TR), due to the simultaneous silencing of TRa and TR beta, thyroid hormone expression was unchanged during decidualization. In summary, we demonstrated that thyroid hormone is essential for decidualization in the endometrium. This is the first in vitro study to find impaired decidualization as a possible cause of infertility in subclinical hypothyroidism (SCH) patients.