Integrin cell adhesion molecules in endometrium of fertile and infertile women throughout menstrual cycle

Integrins (ITGs) are ubiquitous cell adhesion molecules that undergo dynamic alterations during the normal menstrual cycle in human endometrium. The distribution of four different subunits, viz. alpha 4, alpha 6, beta 3 and beta 4 in human endometrial tissue at different stages of the menstrual cycle was studied using immunohistochemical, enzyme immunoassay and SDS-PAGE/Western blot techniques. The specificity of each mAb to their respective ligands viz., laminin (Ln), fibronectin (Fn) and vitronectin (Vn) was done by cell adhesion assays. Both alpha 6 and beta 4 subunits (Ln receptors) expressed primarily on the glandular epithelium, while glandular, stromal and luminal cells expressed predominantly alpha 4 (Fn receptor) and beta 3 (Vn receptor). The appearance of alpha 4 and beta 3 ITG subunits was found to be cell and cycle specific. The levels of both alpha 6 and beta 4 increased throughout the menstrual cycle, while beta 3 subunit appeared abruptly on cycle day 19/20. The immunostaining for alpha 4 and beta 3 was absent in 90% of infertile women. The timing of expression of alpha 4 and beta 3, the two cycle--dependent ITGs framed the putative window of implantation and suggests a role in the diagnosis of infertility. In conclusion, the absence of alpha 4 and beta 3 ITG expression in the endometrium of infertility subjects during mid luteal phase may be associated with defects in uterine function. The defective uterine receptivity may be an unrecognised cause of infertility in these group of women.