通过子宫内膜基因表达签名解读共享的转录基因调节和每个调节类型的相对贡献
Antonio Parraga-Leo1,2, Patricia Sebastian-Leon1, Almudena Devesa-Peiro1,2
1IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), Av. Fernando Abril Martorell 106, Torre A, Planta 1ª, 46026, Valencia, Valencia, Spain.
Reproductive biology and endocrinology : RB&E
|September 12, 2023
概括
这项研究确定了子宫内膜功能的新型调节者,揭示了导致月经周期进展和不孕不育的关键激素和非激素因素. 这些发现为子宫内膜调节和不孕不育的潜在原因提供了新的见解.
科学领域:
- 生殖生物学 生殖生物学
- 基因组学就是基因组学.
- 分子内分泌学分子内分泌学
背景情况:
- 子宫内膜生物标志物研究显示重叠很差,掩盖了像荷尔蒙,转录因子 (TFs) 和microRNAs (miRNAs) 等上游调节者的作用在月经周期功能中.
- 系统地了解子宫内膜的分子相互作用对于准确的调节见解和解释子宫内膜因子不孕症至关重要.
研究的目的:
- 在多项研究中确定子宫内膜基因生物标志物的一致调节剂.
- 分析这些调节者的作用,包括荷尔蒙,TFs和miRNAs,在整个月经周期的子宫内膜转录基因数据集中.
- 在一个独立的队列中验证所选TF的表达.
主要方法:
- 在19个与子宫内膜进展和植入失败相关的基因列表的in-silico分析中确定了目标调节者.
- 从月经周期样本中分析转录组数据集 (n=129),重点关注孕激素和雌激素相关基因.
- 在健康参与者中选择TF基因表达的前性验证 (n=19).
主要成果:
- 3,608个不同的基因与子宫内膜进展/植入失败有关,主要由TFs (89%) 和孕激素 (47%) 调节,较少由miRNAs (5%) 或雌激素 (0%) 调节.
- 确定了311个TF和595个以前与卵巢激素无关的miRNA,包括新型主调节剂CTCF,GATA6,hsa-miR-15a-5p,hsa-miR-218-5p,hsa-miR-107,hsa-miR-103a-3p和hsa-miR-128-3p.
- 在体和体内验证证了在整个月经周期内子宫内选择的基因/miRNAs在子宫内膜中的调节作用.
结论:
- 确定了子宫内膜进展和病理学的新型荷尔蒙和非荷尔蒙调节剂.
- 这项研究为子宫内膜因子不孕症的分子病因提供了新的见解.
- 这些发现突出了关键的TFs和miRNAs作为子宫内膜功能潜在的主调节者.
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