BACKGROUND Although thyroid dysfunction caused by Hashimoto's thyroiditis (HT) is believed to be related to implantation failure due to the underdevelopment of the receptive uterus, it is unknown whether HT itself, even in the euthyroid state, impairs embryo implantation associated with endometrial receptivity defects. To address whether HT itself can affect endometrial receptivity accompanied by implantation alterations, a euthyroid HT model was established in mice. METHODS Female NOD mice were immunized twice with thyroglobulin and adjuvant to induce the experimental HT model. Four weeks after the second treatment, the mice were normally mated, and pregnant ones were sacrificed in implantation window for thyroid-related parameter and steroid hormones measurements by electrochemiluminescence immunoassay and enzyme-linked immunosorbent assay and implantation site number calculation by uptake of Chicago Blue dye. In addition, certain morphological features of endometrial receptivity were observed by hematoxylin-eosin staining and scanning electron microscopy, and the expression of other receptivity markers were analyzed by immunohistochemistry, RT-qPCR or Western Blot. RESULTS HT mice displayed intrathyroidal monocyte infiltration and elevated serum thyroid autoantibody levels without thyroid dysfunction, defined as euthyroid HT in humans. Euthyroid HT resulted in implantation failure, fewer pinopodes, retarded pinopode maturation, and inhibited expression of receptivity markers: estrogen receptor α (ERα), integrin β3, leukemia inhibitory factor (LIF), and cell adhesion molecule-1 (ICAM-1). Interestingly, despite this compromised endometrial receptivity response, no statistical differences in serum estradiol or progesterone level between groups were found. CONCLUSIONS These findings are the first to indicate that HT induces a nonreceptive endometrial milieu in the euthyroid state, which may underlie the detrimental effects of HT itself on embryo implantation.

中文翻译：

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桥本氏甲状腺炎会损害正常甲状腺小鼠的子宫内膜形态和受体标记，从而损害胚胎着床。

背景技术尽管人们认为桥本甲状腺炎（HT）引起的甲状腺功能异常与受体子宫发育不全相关，但与植入失败有关，但即使HT本身处于正常甲状腺状态，HT本身是否也会损害与子宫内膜容受性缺陷相关的胚胎着床仍是未知的。为了解决HT本身是否会影响子宫内膜容受性并伴随着植入改变，在小鼠中建立了甲状腺功能正常的HT模型。方法用甲状腺球蛋白和佐剂免疫雌性NOD小鼠两次，以建立实验性HT模型。在第二次治疗后四周，通常将小鼠交配，孕妇在植入窗口中被处死，通过电化学发光免疫分析和酶联免疫吸附分析测定甲状腺相关参数和类固醇激素，并通过摄取芝加哥蓝染料计算植入位点数量。此外，通过苏木精-伊红染色和扫描电镜观察到子宫内膜的某些形态特征，并通过免疫组织化学，RT-qPCR或Western Blot分析其他受体标志物的表达。结果HT小鼠表现出甲状腺内单核细胞浸润和血清甲状腺自身抗体水平升高，而没有甲状腺功能障碍，定义为人类正常甲状腺HT。甲状腺甲状腺机能亢进导致植入失败，较少的pinopode，延缓pinopode的成熟，并抑制了接受标记的表达：雌激素受体α（ERα），整联蛋白β3，白血病抑制因子（LIF）和细胞粘附分子1（ICAM-1）。有趣的是，尽管子宫内膜容受性反应受到损害，但两组之间的血清雌二醇或孕激素水平没有统计学差异。结论这些发现是第一个表明HT在正常甲状腺状态下诱导非接受性子宫内膜环境的现象，这可能是HT本身对胚胎植入的有害作用的基础。