A Review of Endometrium and Implantation

Steven L. Young, MD, PhD, FACOG

Embryo implantation is one of the most complex, yet critical steps in pregnancy establishment. Achieving a better understanding of this process will result in marked improvements in the care of infertile patients and aid the development of novel contraceptives. Significant progress has been slow to occur, however, due to ethical constraints in humans and profound differences in implantation anatomy and physiology between many model organisms and humans. This enigmatic process is slowly giving way to improved scientific technology and in this issue of Seminars in Reproductive Medicine, an international group of endometrial experts reviews the state of the art and emerging concepts on the role of endometrium during human embryo implantation.

Implantation is the result of a tightly orchestrated communication between embryo and mother, resulting in the invasion of dynamically differentiating maternal endometrium by rapidly dividing and differentiating embryonic trophoblast. One of the forms of endometrial-trophoblast communication is via endometrial secretions, an area not well studied in humans. Gnainsky et al highlight the role of reproductive steroids and cytokines in this highly dynamic process and emphasize the role of synchrony between endometrial and embryonic processes, while Spencer focuses attention on the role of endometrial secretions, known to be critical mediators of implantation in other placental mammals.

The endometrium is a complex and dynamic tissue, even in the absence of pregnancy. It is composed of multiple cell types, including glandular and luminal epithelium, stroma, endothelium, and multiple immunocytes. Endometrium is unique among tissues in that it undergoes proliferation, neovascularization, differentiation, large changes in resident immunocyte number and type, apoptosis, tissue shedding, bleeding, and subsequent healing and regrowth as a normal physiological process. Another unusual, but critical aspect of endometrial function is immunological tolerance of the semiallogeneic embryo as it invades and directly contacts the maternal circulation. Teles and Zenclussen review implantation in the human and mouse with special attention to the role of cellular immunity. Lessey and Young highlight the parallels between cyclic changes in human endometrium and the physiology of acute inflammation, while Haller-Kikkatalo et al examine the role of autoimmunity in the implantation process and discuss why antiendometrial antibodies are not a common cause reproductive dysfunction.

The complexity of the dynamic interaction between maternal endometrium and embryonic trophoblast is made harder to study by the marked differences in implantation anatomy and physiology between most laboratory animal models and humans. However, many old world, nonhuman primates have endometrial cycles and implantation physiology that is highly similar to humans. Thus, nonhuman, old world primates provide the most relevant animal models for study of embryo implantation and Slayden reviews current knowledge about endometrial function in the macaque.

Though a basic understanding of a process fundamental to the creation of a human being is fascinating and a worthwhile area of study in its own right, the application of this knowledge is of greater importance to our patients. To this end, Evans-Hoeker and Young review the impact of intrauterine adhesions on endometrial function and Dior et al discuss recent data that suggest miRNA as a critical mediator of endometrial function and an attractive target for future therapies. Finally, Blesa, Ruiz-Alonso, and Simón review a cutting-edge clinical application of previously identified molecular markers with the potential to significantly enhance the care of infertile couples.