Department of Geriatric Endocrinology, the First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Department of Endocrinology, the First Affiliated Hospital of Nanchang University, Nanchang, 330006, China.
Reprod Biol Endocrinol. 2019 Nov 15;17(1):94. doi: 10.1186/s12958-019-0526-3.
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.
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.
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.
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.
尽管桥本甲状腺炎（HT）引起的甲状腺功能障碍被认为与接受性子宫发育不良导致的着床失败有关，但 HT 本身是否在甲状腺功能正常的情况下损害与子宫内膜容受性缺陷相关的胚胎着床尚不清楚。为了确定 HT 本身是否会影响子宫内膜容受性伴着床改变，我们在小鼠中建立了甲状腺功能正常的 HT 模型。
雌性 NOD 小鼠用甲状腺球蛋白和佐剂两次免疫诱导实验性 HT 模型。第二次治疗后 4 周，小鼠正常交配，在着床窗口处死妊娠小鼠，用电化学发光免疫分析和酶联免疫吸附试验测量与甲状腺相关的参数和类固醇激素，并用 Chicago Blue 染料摄取法计算着床点数量。此外，通过苏木精-伊红染色和扫描电子显微镜观察子宫内膜容受性的某些形态特征，通过免疫组织化学、RT-qPCR 或 Western Blot 分析其他容受性标志物的表达。
HT 小鼠显示甲状腺内单核细胞浸润和血清甲状腺自身抗体水平升高，但无甲状腺功能障碍，定义为人类的甲状腺功能正常的 HT。甲状腺功能正常的 HT 导致着床失败、更少的微绒毛、微绒毛成熟延迟以及抑制受体标志物的表达：雌激素受体α（ERα）、整合素β3、白血病抑制因子（LIF）和细胞间黏附分子-1（ICAM-1）。有趣的是，尽管子宫内膜容受性反应受损，但两组间血清雌二醇或孕酮水平无统计学差异。
这些发现首次表明，HT 在甲状腺功能正常的情况下引起非容受性的子宫内膜环境，这可能是 HT 本身对胚胎着床的不利影响的基础。
