Human Implantation: A Tale of Mutual Maternal and Fetal Attraction1

Abstract

Implantation in humans has been conceptualized largely on the basis of mouse models [1]. It is viewed as a stepwise process involving apposition and adherence of a blastocyst to the endometrium, followed by breaching of the luminal epithelium and, finally, invasion of maternal tissues. This process seems analogous to an invading cancer, with the embryo driving the destruction of endometrial epithelial cells, the enzymatic digestion of stromal matrix, and finally, the invasion of the maternal decidua and inner myometrium (Fig. 1a). Within this context, the role of the maternal decidua is to both tolerate and control the invading semiallogeneic fetal trophoblast. Excessive trophoblast invasion of the uterus presents clinically as placenta accreta or choriocarcinoma, conditions associated with considerable maternal morbidity and, occasionally, death. Conversely, inadequate or deregulated invasion of trophoblast compromises the survival of the fetus and causes a spectrum of pregnancy complications, including miscarriage, intrauterine growth restriction, preeclampsia, and stillbirth. Hence, both excessive and inadequate implantation can have disastrous consequences.