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Suboptimal mid-luteal progesterone concentrations are associated with aberrant endometrial gene expression, potentially resulting in implantation failure
Reproductive BioMedicine Online ( IF 3.7 ) Pub Date : 2020-11-04 , DOI: 10.1016/j.rbmo.2020.10.018
Sutham Suthaporn 1 , Kanna Jayaprakasan 2 , Jim Thornton 1 , Kate Walker 1 , Juan Hernandez Medrano 1 , Marcos Castellanos 3 , Sean May 3 , Lukasz Polanski 1 , Nick Raine-Fenning 4 , Walid E Maalouf 1
Affiliation  

Research question

What is the difference in endometrial transcriptomics between women with normal and with low mid-luteal progesterone during the implantation window?

Design

An endometrial biopsy and serum progesterone concentration were taken from participants during the mid-luteal phase (LH+7 to LH+9). A total of 12 participants were recruited and categorized into two groups based on their progesterone concentrations: normal progesterone (>15 ng/ml, n = 6) and low progesterone (<15 ng/ml, n = 6). Global endometrial gene expression between the two groups was compared by microarray techniques. Principal component analysis was used to display the gene's expression pattern. Pathway and gene ontology enrichment analysis were performed to determine the biological mechanism of progesterone on the endometrium.

Results

Several key genes related to endometrial receptivity were found to be regulated by progesterone. With regard to gene ontology and pathway analysis, progesterone was shown to be mainly involved in structure morphogenesis predominantly during a process of decidualization, extracellular matrix–receptor interaction and cell adhesion. Distinct differences were observed in the transcriptomic profiles between the two groups, indicating potential impairment of endometrial receptivity in women with suboptimal progesterone concentrations. There was a relatively similar pattern of gene expression between endometrial samples with progesterone concentrations approximately 10 ng/ml and >15 ng/ml. Thus, a progesterone concentration of between 10 and 15 ng/ml appears to be sufficient to induce endometrial receptivity.

Conclusions

Abnormally low progesterone below the threshold of 10–15 ng/ml during the implantation window results in aberrant endometrial gene expression that may affect implantation potential.



中文翻译:

次优黄体中黄体酮浓度与异常子宫内膜基因表达有关,可能导致植入失败

研究问题

在植入窗口期间,正常女性和黄体中段孕酮低的女性子宫内膜转录组学有什么区别?

设计

在黄体中期(LH+7 至 LH+9)对参与者进行子宫内膜活检和血清孕酮浓度。共招募了 12 名参与者,并根据其孕酮浓度分为两组:正常孕酮(>15 ng/ml,n  = 6)和低孕酮(<15 ng/ml,n  = 6)。通过微阵列技术比较两组之间的整体子宫内膜基因表达。主成分分析用于显示基因的表达模式。进行通路和基因本体富集分析以确定孕酮对子宫内膜的生物学机制。

结果

发现与子宫内膜容受性相关的几个关键基因受孕酮的调节。关于基因本体和通路分析,黄体酮被证明主要参与结构形态发生,主要是在蜕膜、细胞外基质-受体相互作用和细胞粘附的过程中。两组之间的转录组学特征存在明显差异,表明孕酮浓度欠佳的女性可能会损害子宫内膜容受性。在孕酮浓度约为 10 ng/ml 和 >15 ng/ml 的子宫内膜样本之间存在相对相似的基因表达模式。因此,10 至 15 ng/ml 的孕酮浓度似乎足以诱导子宫内膜容受性。

结论

在植入窗口期间,孕酮异常低于 10-15 ng/ml 的阈值会导致异常的子宫内膜基因表达,这可能会影响植入潜力。

更新日期:2020-11-04
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