Reproductive Medical Center, Renmin Hospital of Wuhan University & Hubei Clinic Research Center for Assisted Reproductive Technology and Embryonic Development, Wuhan, China.
Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan, China.
Front Endocrinol (Lausanne). 2023 Jul 31;14:1144393. doi: 10.3389/fendo.2023.1144393. eCollection 2023.
Successful embryo implantation, is the initiating step of pregnancy, relies on not only the high quality of the embryo but also the synergistic development of a healthy endometrium. Characterization and identification of biomarkers for the receptive endometrium is an effective method for increasing the probability of successful embryo implantation.
Endometrial tissues from 22 women with a history of recurrent implantation failure (RIF) and 19 fertile controls were collected using biopsy catheters on 7-9 days after the peak of luteinizing hormone. Differentially expressed proteins (DEPs) were identified in six patients with RIF and six fertile controls using isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics analysis.
Two hundred and sixty-three DEPs, including proteins with multiple bioactivities, such as protein translation, mitochondrial function, oxidoreductase activity, fatty acid and amino acid metabolism, were identified from iTRAQ. Four potential biomarkers for receptive endometrium named tubulin polymerization-promoting protein family member 3 TPPP3, S100 Calcium Binding Protein A13 (S100A13), 17b-hydroxysteroid dehydrogenase 2 (HSD17B2), and alpha-2-glycoprotein 1, zinc binding (AZGP1) were further verified using ProteinSimple Wes and immunohistochemical staining in all included samples (n=22 for RIF and n=19 for controls). Of the four proteins, the protein levels of TPPP3 and HSD17B2 were significantly downregulated in the endometrium of patients with RIF.
Poor endometrial receptivity is considered the main reason for the decrease in pregnancy success rates in patients suffering from RIF. iTRAQ techniques based on isotope markers can identify and quantify low abundance proteomics, and may be suitable for identifying differentially expressed proteins in RIF. This study provides novel evidence that TPPP3 and HSD17B2 may be effective targets for the diagnosis and treatment of non-receptive endometrium and RIF.
成功的胚胎着床是妊娠的起始步骤，不仅依赖于高质量的胚胎，还依赖于健康的子宫内膜的协同发育。对接受性子宫内膜的特征和鉴定生物标志物是提高胚胎着床成功率的有效方法。
使用活检导管在黄体生成素峰值后 7-9 天从 22 名反复着床失败（RIF）患者和 19 名生育能力正常的对照者中收集子宫内膜组织。使用基于等重标记相对和绝对定量（iTRAQ）的蛋白质组学分析，在 6 名 RIF 患者和 6 名生育能力正常的对照者中鉴定差异表达蛋白（DEPs）。
从 iTRAQ 中鉴定出 263 个 DEPs，包括具有多种生物活性的蛋白质，如蛋白质翻译、线粒体功能、氧化还原酶活性、脂肪酸和氨基酸代谢。使用 ProteinSimple Wes 和免疫组织化学染色在所有纳入的样本（n=22 例 RIF 和 n=19 例对照）中进一步验证了 4 个名为微管蛋白聚合促进蛋白家族成员 3（TPPP3）、S100 钙结合蛋白 A13（S100A13）、17b-羟甾脱氢酶 2（HSD17B2）和α-2-糖蛋白 1，锌结合（AZGP1）的接受性子宫内膜潜在生物标志物。在 RIF 患者的子宫内膜中，TPPP3 和 HSD17B2 的蛋白水平明显下调。
不良的子宫内膜容受性被认为是反复着床失败患者妊娠成功率下降的主要原因。基于同位素标记的 iTRAQ 技术可以鉴定和定量低丰度蛋白质组学，可能适合于鉴定 RIF 中的差异表达蛋白。本研究提供了新的证据，表明 TPPP3 和 HSD17B2 可能是诊断和治疗非接受性子宫内膜和 RIF 的有效靶点。
