Abstract：
Diagnosing Hashimoto thyroiditis (HT) relies on thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) titers. The influence of these antibodies on female infertility remains a subject of debate. This study aims to explore the effect and mechanism of HT on female infertility. First, a single-center cross-sectional study was conducted to investigate whether TgAb and TPOAb are the key factors leading to female infertility. Second, bioinformatic analysis was performed to investigate the potential target molecules and pathways. Third, in vivo experiments were performed to explore the effects of elevated TgAb levels on embryo implantation in a mouse model of autoimmune thyroiditis (AIT). Four hundred and five infertile women and 155 healthy controls were enrolled in the cross-sectional study. Results indicated that the TPOAb titer was associated with female infertility, while the TgAb titer showed no significant association. The increased levels of TgAb and TPOAb are not significantly correlated with anti-Mullerian hormone. Bioinformatic analysis indicated that the common target molecules for HT and female infertility include interleukin (IL)-6, IL-10, matrix metalloproteinase 9, and tumor necrosis factor, suggesting potential regulation through multiple signaling pathways such as HIF-1, VEGF, MAPK, and Th17 cell differentiation. A certain dose of porcine thyroglobulin can successfully establish a mouse model of AIT. In this mouse model, embryo implantation and ovarian reserve remain unaffected by elevated TgAb levels. In conclusion, the serum TPOAb titer was associated with infertility due to female factors but the TgAb titer showed no significant association. A simple increase in serum TgAb titer does not affect embryo implantation and ovarian reserve in the AIT model.
摘要：
桥本甲状腺炎（HT）的诊断依赖于甲状腺球蛋白抗体（TgAb）和甲状腺过氧化物酶抗体（TPOAb）的滴度。这些抗体对女性不孕症的影响仍然是一个争论的话题。本研究旨在探讨HT对女性不孕症的作用及机制。首先,进行了一项单中心横断面研究,以调查TgAb和TPOAb是否是导致女性不孕的关键因素.第二,进行生物信息学分析以研究潜在的靶分子和途径。第三，在自身免疫性甲状腺炎(AIT)小鼠模型中进行体内实验以探讨升高的TgAb水平对胚胎植入的影响.四百零五名不育妇女和155名健康对照者参加了横断面研究。结果表明，TPOAb滴度与女性不孕症有关，而TgAb滴度无显著相关性。TgAb和TPOAb水平的升高与抗苗勒管激素无显著相关性。生物信息学分析表明,HT与女性不孕症的共同靶分子包括白细胞介素(IL)-6、IL-10、基质金属蛋白酶9和肿瘤坏死因子。提示通过多个信号通路如HIF-1，VEGF，MAPK,和Th17细胞分化。一定剂量的猪甲状腺球蛋白可以成功建立小鼠AIT模型。在这个老鼠模型中，胚胎着床和卵巢储备不受TgAb水平升高的影响。总之,血清TPOAb滴度与女性因素导致的不孕相关,但TgAb滴度无显著相关性.血清TgAb滴度的简单增加不会影响AIT模型中的胚胎植入和卵巢储备。
