About 40% of women with infertility and 70% of women with pelvic pain suffer from endometriosis. The pregnancy rate in women undergoing IVF with low endometrial integrin αvβ3 (LEI) expression is significantly lower compared to the women with high endometrial integrin αvβ3 (HEI). Mid-secretory eutopic endometrial biopsies were obtained from healthy controls (C; n=3), and women with HEI (n=4) and LEI (n=4) and endometriosis. Changes in gene expression were assessed using human gene arrays and DNA methylation data were derived using 385 K Two-Array Promoter Arrays. Transcriptional analysis revealed that LEI and C groups clustered separately with 396 differentially expressed genes (DEGs) (P<0.01: 275 up and 121 down) demonstrating that transcriptional and epigenetic changes are distinct in the LEI eutopic endometrium compared to the C and HEI group. In contrast, HEI vs C and HEI vs LEI comparisons only identified 83 and 45 DEGs, respectively. The methylation promoter array identified 1304 differentially methylated regions in the LEI vs C comparison. The overlap of gene and methylation array data identified 14 epigenetically dysregulated genes and quantitative RT–PCR analysis validated the transcriptomic findings. The analysis also revealed that aryl hydrocarbon receptor (AHR) was hypomethylated and significantly overexpressed in LEI samples compared to C. Further analysis validated that AHR transcript and protein expression are significantly (P<0.05) increased in LEI women compared to C. The increase in AHR, together with the altered methylation status of the 14 additional genes, may provide a diagnostic tool to identify the subset of women who have endometriosis-associated infertility.

中文翻译：

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子宫内膜异位症女性在位子宫内膜的遗传和表观遗传变化：与子宫内膜αvβ3整合素表达降低的关联

大约 40% 的不孕症女性和 70% 的盆腔疼痛女性患有子宫内膜异位症。与子宫内膜整合素αvβ3（HEI）高表达的女性相比，子宫内膜整合素αvβ3（LEI）表达低的IVF女性的妊娠率显着降低。中期分泌在位子宫内膜活检取自健康对照（C；n=3），以及患有 HEI（n=4）和 LEI（n=4）和子宫内膜异位症的女性。使用人类基因阵列评估基因表达的变化，并使用 385 K 双阵列启动子阵列获得 DNA 甲基化数据。转录分析显示 LEI 和 C 组分别聚集有 396 个差异表达基因 (DEG) (P<0.01: 275 向上和 121 向下）表明与 C 组和 HEI 组相比，LEI 在位子宫内膜中的转录和表观遗传变化是不同的。相比之下，HEI 与 C 和 HEI 与 LEI 的比较仅分别确定了 83 和 45 度。甲基化启动子阵列在 LEI 与 C 比较中确定了 1304 个差异甲基化区域。基因和甲基化阵列数据的重叠确定了 14 个表观遗传失调的基因，定量 RT-PCR 分析验证了转录组学的发现。分析还显示，与 C 相比，LEI 样品中的芳烃受体 (AHR) 低甲基化并显着过表达。进一步分析证实，与 C 相比，LEI 女性的 AHR 转录物和蛋白质表达显着增加 (P<0.05)。 AHR,