Protein Expression Profile in IVF Follicular Fluid and Pregnancy Outcome Analysis in Euthyroid Women with Thyroid Autoimmunity

The objective of this study is to investigate the influence of the thyroid autoantibodies on the protein expression in follicular fluid and the clinical outcome of assisted reproductive technology. A total of 602 patients treated for infertility were screened; 49 euthyroid women who were positive for thyroid autoantibodies and 63 negative controls were recruited. Follicular fluid samples were analyzed using proteomics. Validation of target proteins in follicular fluid was performed by using parallel reaction monitoring. Differentially expressed proteins in follicular fluid, clinical pregnancy rate, abortion rate, and live-birth rate were analyzed. Clinical pregnancy rates and take-home baby rates in the thyroid autoimmunity (TAI) group were less than in the control group, but abortion rates in the TAI group were higher than in the control group (all P < 0.005). A total of 49 proteins were differentially expressed in the TAI-positive group. In Gene Ontology secondary annotations of all the proteins identified, five types of proteins were associated with the reproductive process. Among 11 proteins quantitatively identified by parallel reaction monitoring, angiotensinogen and fetuin-B were associated with reproduction. These differentially expressed proteins identified in this study involved multiple pathways according to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Our study provides evidence that some differentially expressed proteins between TAI-positive women and controls were associated with the reproductive process and closely related to important physiologic effects, which could partially explain the underlying mechanism link between TAI and the adverse outcomes of assisted reproductive technology.

本研究的目的是探讨甲状腺自身抗体对卵泡液中蛋白质表达以及辅助生殖技术临床结局的影响。共对602例接受不孕症治疗的患者进行了筛选；招募了49名甲状腺自身抗体阳性的甲状腺功能正常女性以及63名阴性对照者。利用蛋白质组学对卵泡液样本进行分析。通过平行反应监测对卵泡液中的目标蛋白质进行验证。分析了卵泡液中差异表达的蛋白质、临床妊娠率、流产率以及活产率。甲状腺自身免疫（TAI）组的临床妊娠率和抱婴回家率低于对照组，但TAI组的流产率高于对照组（所有P < 0.005）。在TAI阳性组中共有49种蛋白质差异表达。在对所有已鉴定蛋白质的基因本体二次注释中，有五类蛋白质与生殖过程相关。在通过平行反应监测定量鉴定的11种蛋白质中，血管紧张素原和胎球蛋白 - B与生殖相关。根据京都基因与基因组百科全书通路富集分析，本研究中鉴定出的这些差异表达蛋白质涉及多种通路。我们的研究提供了证据，表明TAI阳性女性和对照组之间一些差异表达的蛋白质与生殖过程相关，并与重要的生理效应密切相关，这可以部分解释TAI与辅助生殖技术不良结局之间潜在的机制联系。