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4 Molecular Aspects of Placental Development
Wendy P. Robinson1,2 and Deborah E. McFadden1,2
1BC Children's Hospital Research Institute, Vancouver, BC, Canada
2University of British Columbia, Vancouver, BC, Canada
Overview
The placenta is a fetal organ that is discarded after birth, but is essential to ensuring normal development in utero. It regulates fetal growth, protects the fetus from infection and other adverse exposures, as well as generally programming the fetus for good health after birth. Screening for placental disease is an important component to the assessment of the fetus in pregnancy. Reduced placental efficiency can lead to fetal growth restriction (FGR) and/or maternal preeclampsia (PE). This can be caused by genetic changes within the placenta or by environmental influences, such as maternal stress or drug exposure. In this chapter, causes of placental disease and the role of the placenta in diagnosis of fetal health will be reviewed with a focus on genetic associations.
Placental structure
Evaluating the placenta requires an understanding of its unique structure and development. The chorionic villi that compose the placenta are organized into 50–70 distinct tree‐like structures that grow in a clonal manner outwards from the chorionic plate into the basal plate (which interface with the maternal decidua).1 These villi are bathed in maternal blood, from which they sponge up nutrients important for fetal growth. The maternal blood is in direct contact with the outer trophoblast bilayer of the chorionic villi. This bilayer is made up of a multinucleated syncytium derived by fusion of the cytotrophoblast cells that form a single‐cell layer below the syncytium. In addition, some cytotrophoblasts form columns that migrate into and anchor the placenta to the uterine wall. Invasive cells that detach from these columns are termed extravillous trophoblasts (EVTs) and include the interstitial cytotrophoblasts (iCTBs) found in the decidual stroma and those that remodel maternal blood vessels, termed endovascular cytotrophoblasts (eCTBs).1 The inner core of the villi is the chorionic mesenchyme, which includes structural components, and a mix of cells including fetal blood vessels, fibroblasts, pericytes, and Hofbauer cells (placental macrophages). These extraembryonic cells derive from the epiblast of the blastocyst, from which the fetus is also derived.
Placental size is strongly correlated with fetal size; however, there is considerable variation in placental size for any given birthweight.2 The efficiency of the placenta depends on the surface area for exchange, thickness, and density of transporter proteins,3 and birthweight is highly associated with placental weight.4 Interestingly, mean placental size can vary between populations and even within a population over time because of changes in maternal nutrition or other environmental conditions.5
Placental development and function
The placenta is responsible for many functions, which change as pregnancy proceeds.1 In early gestation, the primary roles of the placenta include invasion into the maternal endometrium, remodeling of maternal vasculature, and secretion of hormones important to maintain pregnancy. The placenta subsequently regulates blood flow and nutrient delivery to the fetus, buffers the fetus from adverse environmental effects, and generally performs the functions of multiple organs (lung, brain, kidney, immune system, etc.).
Implantation
During the invasion process, the early trophoblasts produce molecules to help them attach to and invade the uterine wall (e.g. integrins), prevent menstruation (e.g. human chorionic gonadotropin (hCG)), destroy the uterine matrix (e.g. matrix metalloproteinases), and suppress the maternal immune system (e.g. corticotropin‐releasing hormone (CRH)).6, 7 hCG (encoded by CGA and CGB) is one of the earliest hormones expressed from syncytiotrophoblast and stimulates many other processes. Multiple growth factors are important in regulating trophoblast proliferation, including placental growth factor (PlGF), epidermal growth factor (EGF), and transforming growth factor β (TGF‐β).