A molecular staging model for accurately dating the endometrial biopsy [RNA-seq]
Natural variability in menstrual cycle length, coupled with rapid changes in endometrial gene expression, makes it difficult to accurately define and compare different stages of the endometrial cycle. We have developed and validated a novel method for precisely determining endometrial cycle stage based on global gene expression. Our 'molecular staging model' reveals significant and remarkably synchronized daily changes in expression for over 3,400 endometrial genes throughout the cycle, with the most dramatic changes occurring during the secretory phase. Overall design: Total RNA from endometrial biopsy was obtained from women across the menstrual cycle. Cycle stages were evaluated using histopathology. Menstrual cycle stage definitions, assuming a standardized 28 day cycle, and numbers of samples in each group were as follows: Stage 1 = menstrual (days 1–4), 2 = early proliferative (days 5–7), 3 = mid proliferative (days 8–11), 4 = late proliferative (days 12–15, includes 'interval'), 5 = early secretory (days 16–19, or post ovulation days 2-5), 6 = mid secretory (days 20–23, or post ovulation days 6-9), 7 = late secretory (days 24–28, or post ovulation days 10-14).