Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium
Comparative proteomics reveal negative effects of gonadotropin-releasing hormone agonist and antagonist on human endometrium
复制标题
比较蛋白质组学揭示促性腺激素释放激素激动剂和拮抗剂对人子宫内膜的负面影响
DOI：
10.2147/dddt.s201871
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发表时间：
2019-01-01
影响因子：
4.8
通讯作者：
Zhu, Xiao-Bin
中科院分区：
文献类型：
--
作者：
Chen, Qian;Yu, Feng;Zhu, Xiao-Bin
目的：促性腺激素释放激素激动剂（GnRH-a）方案和促性腺激素释放激素拮抗剂（GnRH-ant）方案是体外受精的两种主要促排卵方案，然而，它们的相对功效的比较仍然存在争议。此外，关于它们对子宫内膜容受性的影响存在相互矛盾的数据。因此，本研究调查了GnRH-a和GnRH-ant治疗如何改变分泌中期的子宫内膜。患者和方法：我们比较了正常对照组（n=5）、GnRH-a治疗组（n =5）和GnRH-ant治疗组（n=5）分泌中期人子宫内膜组织的蛋白质组学谱。结果：共鉴定出2088个蛋白质，其中362个蛋白质表达差异显著。使用M Fuzz算法分析的模糊c均值聚类（FCM）显示，与对照组相比，GnRH-a和GnRH-ant组中相同的87个蛋白质发生显著变化。此外，基因本体论（GO）分析表明，这87个，下调的蛋白质与能量代谢和上调的蛋白质与细胞骨架的维护。参与补体介导的免疫的上调蛋白质存在于151种蛋白质中，这些蛋白质仅在GnRH-ant组中表现出显著不同的表达。结论：我们证明，比较蛋白质组学分析是有用的访问子宫内膜容受性，这似乎更强烈的损害GnRH-ant比GnRH-a治疗。能量代谢和免疫反应可能是子宫内膜容受性的重要生物学机制。
Purpose: The two major ovarian-stimulation protocols for in vitro fertilization are gonadotropin-releasing hormone agonist (GnRH-a) protocol or GnRH antagonist (GnRH-ant) protocol; however, comparisons of their relative efficacy remain controversial. Additionally, conflicting data exist regarding their effects on endometrial receptivity. Thus, this study investigated how GnRH-a and GnRH-ant treatments alter the endometrium during the mid-secretory phase. Patients and methods: We compared proteomic profiles across human endometrium tissues of mid-secretory phase from normal control humans (n=5), patients treated with GnRH-a (n=5), and patients treated with GnRH-ant (n=5). Results: We identified 2088 proteins, with 362 that exhibited significantly different expression. Fuzzy c-means clustering (FCM) using the M Fuzz algorithm analysis showed that the same 87 proteins changed significantly in both the GnRH-a and GnRH-ant groups compared with those in the control. Moreover, Gene Ontology (GO) analysis showed that, of these 87, downregulated proteins were associated with energy metabolism and upregulated proteins were linked to cytoskeleton maintenance. Upregulated proteins involved in complement-mediated immunity were present in 151 proteins that exhibited significantly different expression in the GnRH-ant group only. Conclusion: We demonstrated that comparative proteomic analysis is useful for accessing endometrial receptivity, which seemed more strongly impaired by GnRH-ant than GnRH-a treatments. Our findings also revealed that energy metabolism and immunity response may be the key biological mechanisms underlying human endometrial receptivity.