We recently studied whether the endometrium of women with endometriosis might be abnormal during the implantation phase of the menstrual cycle. We evaluated the expression of biomarkers of implantation, glycodelin A (GdA), osteopontin (OPN), lysophosphatidic acid receptor 3 (LPA3), and HOXA10, in eutopic endometrium of women with and without endometriosis using a prospective observational study design. Twenty-four women with endometriosis and 23 healthy volunteers of similar age underwent an endometrial biopsy in the secretory phase and the immunohistochemical staining intensity and localization of GdA, OPN, LPA3, and HOXA10 was evaluated. Endometrial GdA expression was significantly reduced in patients after cycle day 22. The endometrium from women with endometriosis also showed decreased expression of OPN in the late secretory phase and LPA3 and HOXA10 expression in the midsecretory and late secretory phases. The decreased expression of these four biomarkers of implantation may indicate impaired endometrial receptivity in patients with endometriosis, providing one explanation for the subfertility observed even in women with few pelvic implants. Because many of these markers are progesterone dependent, these findings suggest the possibility of reduced endometrial progesterone action in this population. Nuclear and cytoplasmic endometrial expression of Indian hedgehog increased from the late proliferative to mid and late secretory phases in 26 healthy volunteers compared with 30 women with endometriosis. The abnormal expression of Indian hedgehog protein in women with endometriosis suggests a resistance to P action.
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