While the embryonic epiblast is undergoing cell movements reminiscent of those seen in reptilian or avian gastrulation, the extraembryonic cells are forming the placenta, a distinctly mammalian set of tissues that enable the embryo to survive within the maternal uterus. Although the initial trophoblast cells of mice and humans divide like most other cells of the body, they give rise to a population of cells in which nuclear division occurs in the absence of cytokinesis. The original trophoblast cells constitute a layer called the cytotrophoblast, whereas the multinucleated cell type forms the syncytiotrophoblast. The cytotrophoblast initially adheres to the endometrium through a series of adhesion molecules, as we saw above. Moreover, cytotrophoblasts contain proteolytic enzymes that enable them to enter the uterine wall and remodel the uterine blood vessels so that the maternal blood bathes fetal blood vessels. The syncytiotrophoblast tissue is thought to further the progression of the embryo into the uterine wall by digesting uterine tissue. The cytotrophoblast secretes paracrine factors that attract maternal blood vessels and gradually displace their vascular tissue such that the vessels become lined with trophoblast cells (Fisher et al. 1989; Knöfler 2010). Shortly thereafter, mesodermal tissue extends outward from the gastrulating embryo (see textbook Figure 12.19C). Studies of human and rhesus monkey embryos have suggested that the yolk sac as well as primitive streak-derived cells contribute this extraembryonic mesoderm (Bianchi et al. 1993).
The extraembryonic mesoderm joins the trophoblastic extensions and gives rise to the blood vessels that carry nutrients from the mother to the embryo. The narrow connecting stalk of extraembryonic mesoderm that links the embryo to the trophoblast eventually forms the vessels of the umbilical cord. The fully developed extraembryonic organ, consisting of trophoblast tissue and blood vessel-containing mesoderm, is the chorion, and it fuses with the uterine wall decidua to create the placenta. Thus the placenta is an organ derived from two genetically different organisms.
The chorion may be very closely apposed to maternal tissues while still being readily separable from them (as in the contact placenta of the pig), or it may be so intimately integrated with maternal tissues that the two cannot be separated without damage to both the mother and the developing fetus (as in the deciduous placenta of most mammals, including humans). Beyond their role in nourishing the embryo, placentas are endocrine and immunological organs. They produce hormones (such as progesterone) that enable the uterus to retain the pregnancy and accelerate mammary gland development. Recent studies also suggest that the placenta generates several mechanisms that block the mother’s immune system from attacking foreign substances produced by the embryo or fetus (Warning et al. 2011; Rowe et al. 2012).
Figure 1, Part A shows the relationships between the embryonic and extraembryonic tissues of a 6.5-week human embryo. The embryo is seen encased in the amnion and is further shielded by the chorion. The blood vessels extending to and from the chorion are readily observable, as are the villi that project from the outer surface of the chorion. These villi contain the blood vessels and allow the chorion to have a large area exposed to the maternal blood. Although fetal and maternal circulatory systems normally never merge, diffusion of soluble substances can occur through the villi (Figure 1, Part B). In this manner, the mother provides the fetus with nutrients and oxygen, and the fetus sends its waste products (mainly carbon dioxide and urea) into the maternal circulation. The maternal and fetal blood cells usually do not mix, although a small number of fetal red blood cells are seen in the maternal blood circulation.
1. There are numerous types of placentas, and the extraembryonic membranes form differently in different orders of mammals (see Cruz and Pedersen 1991). Although mice and humans gastrulate and implant in a similar fashion, their extraembryonic structures are distinctive. It is very risky to extrapolate developmental phenomena from one group of mammals to another. Even Leonardo da Vinci got caught (Renfree 1982). His remarkable drawing of the human fetus inside the placenta is stunning art but poor science: the placenta is that of a cow.
Bianchi, D. W., L. E. Wilkins-Haug, A. C. Enders and E. D. Hay. 1993. Origin of extraembryonic mesoderm in experimental animals: Relevance to chorionic mosaicism in humans. Am. J. Med. Genet. 46: 542–550.
Cruz, Y. P. and R. A. Pedersen. 1991. Origin of embryonic and extraembryonic cell lineages in mammalian embryos. In Animal Applications of Research in Mammalian Development. Cold Spring Harbor Press, Cold Spring Harbor, NY, pp. 147–204.
Fisher, S. J., T.-Y. Cui, L. Zhang, L. Hartman, K. Grahl, Z. Guo-Yang, J. Tarpey and C. H. Damsky. 1989. Adhesive and degradative properties of the human placental cytotrophoblast cells in vitro. J. Cell Biol. 109: 891–902.
Knöfler, M. 2010. Critical growth factors and signalling pathways controlling human trophoblast invasion. Int. J. Dev. Biol. 54: 269–280.
Renfree, M. B. 1982. Implantation and placentation. In C. R. Austin and R. V. Short (eds.), Embryonic and Fetal Development. Cambridge University Press, Cambridge, pp. 26–69.
Rowe, J. H., J. M. Ertelt, L. Xin and S. S. Way. 2012. Pregnancy imprints regulatory memory that sustains anergy to fetal antigen. Nature 490: 102–106.
Warning, J. C., S. A. McCracken and J. M. Morris. 2011. A balancing act: Mechanisms by which the fetus avoids rejection by the maternal immune system. Reproduction 141: 715–724.