Yang Fei, Qi Ting, McRae Allan F, Rogers Peter A W, Montgomery Grant W, Mortlock Sally
The Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
School of Life Sciences, Westlake University, Hangzhou, Zhejiang 310024, China.
iScience. 2025 Jul 24;28(9):113207. doi: 10.1016/j.isci.2025.113207. eCollection 2025 Sep 19.
The endometrium, essential for reproduction, undergoes cyclical shedding, remodeling, and regeneration. Using a large endometrial transcriptomic dataset ( = 206), we identified RNA splicing and transcript isoform-level changes across the menstrual cycle and in endometriosis, findings not seen in gene-level analyses. Transcriptomic differences were most pronounced in the mid-secretory (receptive) phase in endometriosis samples. By integrating genotype data, we found evidence of -genetic effects on splicing in endometrium, identifying 3,296 splicing quantitative trait loci (sQTLs) with the majority of genes with sQTLs (67.5%) not discovered in the gene level eQTLs analysis, indicating the splicing-specific effects. Integrating the sQTLs with the endometriosis genome-wide association study (GWAS) data, we identified two genes ( and ) that were significantly associated with endometriosis risk through genetically regulated splicing events. Overall, this study detected transcript isoform-level and RNA splicing level specific changes, providing insights into the dynamic changes in transcriptomic regulation in endometrium and its association with endometriosis.
子宫内膜对于生殖至关重要，会经历周期性的脱落、重塑和再生。利用一个大型子宫内膜转录组数据集（n = 206），我们在整个月经周期以及子宫内膜异位症中识别出了RNA剪接和转录本异构体水平的变化，这些变化在基因水平分析中并未观察到。转录组差异在子宫内膜异位症样本的分泌中期（接受期）最为明显。通过整合基因型数据，我们发现了基因对子宫内膜剪接的影响证据，识别出3296个剪接数量性状位点（sQTL），其中大多数具有sQTL的基因（67.5%）在基因水平的表达数量性状位点（eQTL）分析中未被发现，这表明了剪接特异性效应。将sQTL与子宫内膜异位症全基因组关联研究（GWAS）数据相结合，我们识别出两个基因（ 和 ），它们通过基因调控的剪接事件与子宫内膜异位症风险显著相关。总体而言，本研究检测到了转录本异构体水平和RNA剪接水平的特异性变化，为子宫内膜转录组调控的动态变化及其与子宫内膜异位症的关联提供了见解。
