**1.2. Placenta development**

Placenta development is a continuous process that starts during early embryological stages, even before gastrulation occurs. Four to five days after fecundation, the morula (solid mass of cells called blastomers) has reached the uterus. The appearance of a fluid-filled inner cavity marks the transition from morula to blastocyst and is accompanied by cellular differentiation: the surface cells become the trophoblast (giving rise to extraembryonic structures, including the placenta and the umbilical cord) and the inner cell mass gives rise to the embryo [3]. Just before the implantation into the endometrium, the internal cell mass or embryoblast, goes through important changes such as cellular reorganization that gives place to a top layer, the epiblast and a bottom layer named hypoblast or primitive endoderm. Some extraembryonic tissues such as the amnion derive from the epiblasts that delimit the amniotic cavity that hosts the embryo during pregnancy. Because of the increase in production of amniotic liquid during gestation, the amnion will expand, and merge with the trophoblast to give rise to the amnionchorionic membrane. Another of the earliest differentiation events in human embryogenesis takes place in the trophoblast with the development of the external syncytiotrophoblast

**Figure 1.** First stage in the interaction between fetal and maternal blood circulation. The syncytiotrophoblast erodes maternal vessels.

and the internal cytotrophoblast. The cytotrofoblast is constituted by highly proliferative mononucleated cells. Syncytiotrophoblast is formed by fusion of cytotrophoblastic cells and has high invasive capacity. This syncytium is responsible for the implantation or anchorage of the blastocyst within the uterine walls.

The lytic activity of the syncytiotrophoblast, which is responsible for the degradation of the matrix of the endometrium, reaches the uterine capillaries, eroding them. As a result of vascular damage, maternal blood comes out to the syncytiotrophoblast where it forms lacunae; this lacunar stage is the first one toward a fetomaternal circulation. At the same time, the epithelial-like cells of the cytotrofoblast, which have continued proliferating, form accumulations that project toward the syncytiotrophoblast forming the chorionic villi that penetrate the decidua basalis [4]. These finger-like structures (cytotrophoblast covered with syncytiotrophoblast) are invaded by an extraembryonic mesoderm that, in the fourth week after fertilization, gives rise to blood vessels within each villi which makes possible the establishment of the interaction between the fetal circulation, in these embryo vessels, and the maternal blood contained in the trophoblastic lacunae (**Figure 1**). The different layers of the trophoblast (the cytotrophoblast and the syncytiotrophoblast), the basal membranes of the fetal vessels, and the vascular endothelium of these vessels constitute the placenta barrier that regulates the metabolite exchange between both circulations (fetal and maternal). It has been estimated that this exchange surface is about 5 m<sup>2</sup> at week 28 of gestation and reaches 10–11 m<sup>2</sup> at term [5]. Moreover, this barrier undergoes a progressive thinning throughout pregnancy going from 10 microns at the beginning to 1 or 2 microns at the end of the gestation [6]. The umbilical cord connects placenta to the fetus. It is a narrow tube that contains two arteries and one vein to transport metabolites between mother and fetus.
