Placenta Development & Pathologies

The placenta is a mulit-functional organ that ensures nutrient and gas exchange between maternal and offspring circulation. In Weeks 2-8, we'll cover trophoblast differentiation: during implantation, the trophoblast gives rise to the cytotrophoblast and synctiotrophoblast; these layers are pivotal in establishing the fetal side of the placenta. In week 2, the extra-embryonic mesodermal layers arise. The first trimester is relatively hypoxic; though the synctiotrophoblast makes contact with maternal sinusoids, it also plugs maternal vessels to protect the embryo from high levels of oxygen in maternal blood, which is thought to be toxic to early developmental processes. Final stages of implantation; a fibrin coagulum seals endometrium at implantation site. The outermost multi-nucleated synctiotrophoblast, which features spaces, called lacunae. Cytotrophoblast is deep to synctiotrophoblast; it comprises a single cell layer. Recall that the cytotrophoblast and synctiotrophoblast are derived from the trophoblast layer of the blastocyst (more specifically, the trophoblast gave rise to cytotrophoblast cells, some of which then differentiated to form the synctiotrophoblast). Bilaminar embryonic disc:

• The epiblast, which has ectodermal origins, and comprises columnar cells.
• The hypoblast, which comprises cuboidal cells; because of its endodermal origins, it is also referred to as the primitive endoderm.

Cells from the hypoblast migrate to form the exocoelomic membrane (aka, Heuser's membrane), which encloses the exocoelomic cavity (aka, primary yolk sac). Synctiotrophoblast lacunae make contact with maternal sinusoids. Extraembryonic mesoderm separates the exocoelomic membrane and cytotrophoblast.

• It is thought that this mesodermal tissue originates from the hypoblast, and, perhaps, the trophoblast.
• The extraembryonic mesoderm closest to the cytotrophoblast comprises the somatic mesoderm.
• The extraembryonic mesoderm surrounding the exocoelomic membrane is the splanchic mesoderm.
• Spaces form within the mesoderm; these spaces become continuous to form a true separation between the splanchnic and somatic mesodermal layers.

The endometrium is healed and the fibrin coagulum is gone. Synctiotrophoblast is greatly expanded into the uterine wall and formed extensive connections with the maternal blood supply. The cytotrophoblast begins to transform: it gives rise to primary villi, which extend into the synctiotrophoblast. As we'll see, these villi become the functional sites of gas exchange between the mother and fetus. Extraembryonic mesoderm:

• The outer somatic layer of extraembryonic mesoderm is adjacent to the cytotrophoblast.
• The inner splanchnic layer surrounds the embryo proper.
• The space between them is the chorionic cavity.
• Mesodermal connecting stalk joins the two mesodermal layers and suspends the embryo within the chorionic cavity.

This connection will later become the umbilical cord, which carries the umbilical vessels. Bilaminar embryo:

• Epiblast surrounds the amniotic cavity.
• Primary yolk sac has regressed; the secondary yolk sac now faces the hypoblast.

By the end of week three, dramatic transformations re-organize these tissues. Cells of the cytotrophoblast layer migrated to form the outer cytotrophoblast shell. Synctiotrophoblast lacunae are filled with blood from the maternal sinusoids; notice that cytotrophoblast cells surround them. Somatic extraembryonic mesoderm has infiltrated the cytotrophoblastic primary villi, and begins to develop embryonic vasculature, giving rise to Tertiary Villi. Thus, the blood-filled lacunae now fill the intervillous spaces (spaces between the tertiary villi). Somatic mesoderm gives rise to the chorionic plate, which surrounds the chorionic cavity. Be aware that we've skipped some transitional events that occurred earlier during week 3 (for example, the transition from primary to secondary and secondary to tertiary villi). During weeks 4-8, the overall organization of embryonic tissues remains as it is at the end of week 3. However, extensive vascular remodeling lays the groundwork for the mature placenta. Chorionic plate gives rise to the mesodermal cores and blood vessels of the tertiary villi. Cytotrophoblast covers the mesodermal core of the tertiary villi, and, also, forms the outer cytotrophoblast shell; cellular columns connect outer shell and tertiary villi. Synctiotrophoblast lines the cytotrophoblast of the villi. Intervillous spaces are continuous with maternal blood vessels, and lined by synctiotrophoblast. As we learn elsewhere, these villi are the sites of gas, nutrient, and waste exchange between the maternal and fetal environments. The human placenta is hemochorial, which means it allows direct contact between uterine blood and fetal tissues. As we'll see, chorionic villi are the functional units of the placenta; the chorionic villi are the sites of exchange between the uterus and fetus. Fetal growth is dependent upon sufficient oxygen, nutrients, and other substances provided in the uterine blood, and insufficient vascular remodeling has major clinical consequences, including fetal growth restriction, eclampsia, and even spontaneous abortion. The placenta is derived from both uterine and embryonic tissues. We'll begin at approximately week 9, when differential growth and regression of the chorionic villi initiates formation of the mature placenta. Within the uterine cavity we show the embryo. The embryo is suspended within the amniotic cavity, which is bound by the amniotic membrane. The chorion plate grows thick with villi at the embryonic pole; this area is called the chorion frondosum. The thinner area of the chorion plate is called the chorion laeve; this is where the villi regress. The chorionic cavity surrounds the amniotic cavity and embryo. The endometrium is now called the decidua. The regions of the decidua are named according to their location in reference to the embryo: The decidua basalis is adjacent to the chorion frondosum. The decidua capsularis encapsulates the embryo. The decidua parietalis is on the opposite side of the embryo. By week 20, expansion of the embryo pushes these layers against each other; they fuse and form the mature placenta. To show this, we again outline the myometrium and show that a mucus plug blocks the cervical opening. We show the growing fetus in the amniotic cavity, bound by the amniotic membrane. At the aembryonic pole, the chorion laeve is greatly reduced, and fused with the amniotic membrane; at the embryonic pole, it is thick with chorionic villi. At the embryonic pole, the decidua basalis joins the chorion frondosum to form the placenta. At the opposite side, the decidua capsularis has regressed the decidua parietalis fuses with the chorion leave. The chorionic cavity has been obliterated, and that the uterine cavity is greatly reduced due to the growth of the fetus. The placenta is a temporary, multi-function organ, and that fetal growth is driven by dynamic interactions between the parent and fetus. In healthy pregnancies, both fetal and parental needs are met by physiological processes that operate for mutual benefit. However, when parental health is poor, physiological compromises are made that put the parent and/or fetus at greater risk. Let's see how the placenta serves as an interface between uterine and fetal environments. On the fetal side, we show the amniotic membrane, which gives the surface a smooth, shiny appearance; show that the umbilical cord carries the umbilical arteries and vein from the placenta to the fetus. The chorionic plate gives rise to chorionic villi; blood vessels travel within the chorionic plate to reach the villi. On the uterine side we show the decidual, aka, basal plate: the decidua forms septa, which demarcate cotyledons; cotyledons give the uterine surface of the placenta a bumpy appearance. "Anchoring villus" makes contact with the decidua; "floating" villi do not make contact. The intervillous space lies between the chorion and decidual plate; uterine vasculature passes through the decidua and opens to the intervillous space. Notice the cork-screw appearance of a spiral artery of the uterus. Recall that the intervillous spaces are derived from connections formed between the synctiotrophoblast and uterine sinusoids during early embryonic development (see our notes for review of early placental development). Materials are transferred across the villous surface: nutrients and oxygen leave the uterine blood, enter the intervillous space, cross the villous surface, and then enter the fetal vessels; Wastes and other materials exit the fetal blood, cross the villous surface, enter the intervillous space, and enter the uterine veins. With the basic anatomical context and pathways established, let's consider some key roles of the placenta. Exchange of materials occurs in both directions across the placenta: From the uterine side, oxygen, nutrients, hormones, antibodies, and some drugs enter the fetal circulation. From the fetal side, carbon dioxide and other metabolic wastes, hormones, and red blood cell antigens enter the parental circulation. The placenta produces hormones that are necessary for the maintenance of pregnancy, including human chorionic growth hormone, estrogen, and progesterone. The placenta also produces placental lactogen and growth hormone, which induce parental insulin resistance later in pregnancy; this ensures that parental nutrients are readily available for fetal growth. The placenta also prohibits passage of many pathogens from the mother to the fetus. However, there are several important exceptions to this rule, which are captured in the TORCHeS mnemonic: Toxoplasmosis, Others, Rubella, Cytomegalovirus, and Herpes simplex can all traverse the placenta. The Zika virus is another important exception: fetal infection can result in serious birth defects, including microcephaly. Lastly, as a clinical correlation, let's show two important placental disorders that can result in hemorrhaging. First, we show placenta previa, in which the placenta sits low in the uterus, covering the opening of the cervix; this positioning may self-correct over the course of a pregnancy. We also show an abnormally invasive placenta; this condition occurs along a spectrum, from strong adherence of the placenta to the uterine wall to invasion through the uterine wall and attachment to nearby structures, such as the urinary bladder. Prior cesarean section is a key risk factor, because the uterine scar provides a surface for placental invasion.