The fertilized ovum undergoes several rounds of cell division as described in Figure1 and reaches the uterus as a blastocyst, still surrounded by the zona pellucida and little changed in size from the unfertilized ovum. The blastocyst consists of a layer of trophoblasts and an inner cell mass, both of which surround a cavity, the blastocoele (Figure 2A). The blastocyst remains near but not attached to the uterine lining for a day or two, being nourished by the secretions of the endometrial glands. Near the end of this period, the endometrial glands secrete an enzyme which dissolves the zona pellucida in a process referred to as “hatching” (not shown). Shortly thereafter, the trophoblastic cells differentiate into an outer layer, the syncytiotrophoblast, and an inner layer, the cytotrophoblastic cells. The development of the embryo to this point and the preparation of the uterine lining for its reception are closely synchronized events. Delay in the embryo’s development is likely to result in the failure of the potential pregnancy. For this reason, this pre-implantation stage is one of a high rate of fetal loss.
Fig1. Overview of ovulation, fertilization, implantation. Fertilization, which takes place within 24 hours of ovulation, is designated as Day 0. The first cleavage is accomplished on day 2 and is followed by more rapid divisions, resulting, on day 4, in a compact ball of 16–32 cells called the morula. Continued division without an increase in size leads to the blastocyst which arrives in the uterus consisting of 70–100 cells on day 5 following fertilization. The process of implantation takes place on days 7–9 and is shown in Figure2.
Fig2. Implantation. Implantation of the blastocyst takes place on days 7–10 following fertilization of the ovum. A. The blastocyst (Figure 1, day 5) consists of a layer of trophoblastic cells, which will develop into the fetal portion of the placenta, an inner cell mass which will develop into the embryo, and a cavity, the blastocoel, which will become the yolk sac. B. The trophoblastic cells of the blastocyst attach to the epithelial cells of the endometrium and some of them form a syncytium (a large multinucleate cell resulting from fusion of many cells). This portion of the structure is the syncytiotrophoblast, which begins to invade the uterine lining. C. The blastocyst continues to move into the stroma of the endometrium and the amniotic cavity appears. D. Uterine tissue grows over the blastocyst and irregular blood sinusoids appear in the syncytiotrophoblast.
During the implantation window (days 20–24 of the menstrual cycle) implantation sites known as pinopods develop in the endometrial epithelium. The cells at these sites express chemokines (molecules that attract cells) and cell adhesion molecules such as mucins, integrins, and troponins. At one of these sites, the syncytiotrophoblastic cells invade the endometrium by secreting their own cell adhesion molecules as well as enzymes that break down stromal cells (Figure 2B). In the deciduoma response, the stromal cells begin to grow over the invading conceptus (Figure 2C) until implantation is complete on about day 10 following fertilization (Figure 2D). By this time sinusoids derived from endometrial spiral arteries and containing maternal blood have appeared in the syncytiotrophoblast, an initial step in establishment of the maternal–fetal blood circulatory system.
