Molecular markers of implantation: clinical implications.

The endometrium has been conventionally studied using histologic criteria. Our understanding of endometrial physiology has been advanced tremendously by research into the molecules that mediate its development and function. These molecules demonstrate a dynamic expression pattern through the menstrual cycle and have been implicated in endometrial growth, differentiation, and receptivity. These molecules include secreted proteins (endometrial bleeding-associated factor, glycodelin-A, insulin-like growth factor binding protein-1), cell-surface receptors (integrins), and nuclear transcription factors (HOXA10 and HOXA11). The homeobox genes Hoxa10 and Hoxa11 are necessary for implantation because mice with mutations in these genes exhibit a failure of implantation. HOXA10 and HOXA11 have been shown to be important for implantation in humans as well. Knowledge of endometrial molecular dynamics may now be used to enhance our ability to diagnose implantation defects. It may soon be possible to treat individual molecular defects by protein supplementation or gene therapy.