L-Selectin Ligand in Endometrium From Women With Infertility

Abstract

To evaluate the pattern and intensity of the L-Selectin ligand in the endometrium from both fertile and infertile women throughout the menstrual cycle and during the window of implantation. This is a retrospective study on 48 endometrial samples from reproductive-aged women at various times in the menstrual cycle. Immunohistochemistry and western blot analysis was performed using the antibody, MECA-79, which recognizes the ligand for the L-selectin adhesion molecule. Endometrial biopsies were obtained from both fertile and infertile women during the menstrual cycle. Secretory phase samples were timed to the urinary LH surge. Overall, 48 samples were compared. Eighteen biopsies from normal cycling women included 3 proliferative, 3 early secretory (day15-19), 10 mid-secretory (day 20 to 24) and 2 late secretory phase (day 25-28). Additionally, mid-secretory samples were obtained from 7 women with PCOS in ovulatory cycles and 17 women with endometriosis, and 6 samples with significant histologic delay and luteal phase defect (LPD). These were compared to biopsies from normal fertile women in the mid-secretory phase. Statistical analysis was performed using ANOVA with Bonferroni correction with significance assigned at the 95% confidence interval (p < 0.05). The L-selectin ligand was absent during the proliferative phase and peaks during the early and mid-secretory phase in both glands (p=0.002 and 0.003) and lumen (p=0.004 and 0.005). In this first comparison of the L-selectin ligand in infertile and fertile women, we show that there was a slight decrease in overall expression of this antigen in glandular epithelium of women with PCOS and endometriosis (P =0.07 and P=0.052, respectively), compared to normal controls. However, in a subset of these patients the loss of L-selectin ligand was greater. A significant decrease was seen in the luminal expression in both PCOS and endometriosis patients (p=0.02 and p=0.048, respectively). Endometrium from women with LPD also had significantly less MECA79 staining on both glands (p=0.02) and lumen (p = 0.03), respectively. These findings were corroborated using western blot analysis. Given the suspected role in L-selectin as the attachment receptor for the human embryo, these results shed light on the maternal-fetal interface during the implantation window. The identification of depressed expression of luminal and glandular L-selectin ligand in a subset of women with PCOS and endometriosis provides further evidence for selective defects in endometrial receptivity in certain groups of women with infertility. The L-Selectin ligand is significantly reduced in some women with PCOS and endometriosis at the time of implantation. Further studies will be required to investigate the mechanism for this decrease, but evidence points to a reduction in the N-acetylglucosamine-6-O-sulfotransferase activity. Screening for such defects may be important prior to IVF or other infertility treatments.