Liu Yang, Hou Xianping, Jia Zhangwei, Zhao Shaotong, Zhou Tingting, Liao Jia, Zhang Qian, Yan Junhao, Ni Tianxiang
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University, Jinan, Shandong, China.
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.
Am J Reprod Immunol. 2025 Jan;93(1):e70044. doi: 10.1111/aji.70044.
Alterations in lipid metabolism were reported to impact human fertility; however, there is limited evidence on the association of lipid metabolism with embryo implantation as well as the etiology of recurrent implantation failure (RIF), especially regarding arachidonic acid metabolism.
Experimental verification research (16 RIF patients and 30 control patients) based on GEO database analysis (24 RIF patients and 24 control patients). The methods in bioinformatics included differential gene screening, functional enrichment analysis, protein-protein interaction network, cluster analysis, weighted gene co-expression network analysis, and so forth. RIF patients were recruited for the experimental validation section. The endometrial samples in the mid-luteal phase were collected and subjected to quantitative real-time PCR detection.
Genes related to oxidative stress were differentially expressed and 17 different types of immune cells exhibited diverse infiltration in three RIF subgroups with different arachidonic acid metabolism. HPGDS, ALOX12, and TBXAS1 showed a strong positive correlation with the infiltration of NK cell, on the contrary, GGT6, PLA2G12A, and PTGS2 showed a strong negative correlation. The overall expression of AAMRGs was positively correlated with the infiltration of activated CD8 T cell, macrophage, natural killer cell, and T follicular helper cell.
The cluster of arachidonic acid metabolism-related genes (AAMRGs) was abnormally expressed and positively associated with excessive oxidative stress as well as extensive infiltration of immune cells, including NK cells among RIF patients. Considering the high heterogeneity of the etiology of RIF, our study utilized the expression of AAMRGs as a typing basis to provide a new understanding of endometrial receptivity from the perspective of lipid metabolism and immune regulation in unexplained RIF couples, providing directions for its etiology and future basic research.
据报道，脂质代谢改变会影响人类生育能力；然而，关于脂质代谢与胚胎着床以及反复着床失败（RIF）病因之间关联的证据有限，尤其是在花生四烯酸代谢方面。
基于GEO数据库分析（24例RIF患者和24例对照患者）进行实验验证研究（16例RIF患者和30例对照患者）。生物信息学方法包括差异基因筛选、功能富集分析、蛋白质 - 蛋白质相互作用网络、聚类分析、加权基因共表达网络分析等。招募RIF患者进行实验验证部分。收集黄体中期的子宫内膜样本并进行定量实时PCR检测。
与氧化应激相关的基因存在差异表达，17种不同类型的免疫细胞在具有不同花生四烯酸代谢的三个RIF亚组中表现出不同的浸润情况。HPGDS、ALOX12和TBXAS1与NK细胞浸润呈强正相关，相反，GGT6、PLA2G12A和PTGS2与NK细胞浸润呈强负相关。AAMRGs的整体表达与活化的CD8 T细胞、巨噬细胞、自然杀伤细胞和滤泡辅助性T细胞的浸润呈正相关。
花生四烯酸代谢相关基因（AAMRGs）簇在RIF患者中异常表达，且与过度氧化应激以及包括NK细胞在内的免疫细胞广泛浸润呈正相关。考虑到RIF病因的高度异质性，我们的研究利用AAMRGs的表达作为分型依据，从脂质代谢和免疫调节的角度为不明原因RIF夫妇的子宫内膜容受性提供了新的认识，为其病因及未来基础研究提供了方向。
