Читать книгу Genetic Disorders and the Fetus - Группа авторов - Страница 144

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). In addition, microparticles, such as microvesicles (0.1–2 μm) and exosomes (30–100 nm), are released by the placental syncytium into maternal decidua and blood and may play a role in early maternal immune suppression and vascular remodeling.^8–11 These microparticles provide a rich source of placental derived material detectable in maternal blood early in pregnancy that has the potential to be used in monitoring the pregnancy.

Failure of implantation and invasion can lead to early miscarriage. The majority of miscarriages occurring in the first trimester of pregnancy are associated with chromosome abnormalities, with trisomy, triploidy, and 45,X accounting for the vast majority of these.^{12, 13} The reasons for implantation failure in chromosomally abnormal cases are likely complex, involving dysregulation of multiple important genes that then impede trophoblast growth and invasion. Trisomy for chromosomes 1, 11, and 19 are rarely observed even in early miscarriages, and presumably do not survive to clinical detection of pregnancy. Chromosome 19 not only has the highest gene density of any chromosome, but is sometimes referred to as the “placenta chromosome” because of the numerous placenta‐specific genes located on it, including the highly expressed pregnancy‐specific glycoprotein cluster (PSG),¹⁴ and the maternally imprinted chromosome 19 miRNA cluster (C19MC), the largest microRNA cluster in humans.¹⁵ Failure of implantation among genetically normal conceptuses can be due to a nonreceptive maternal environment resulting from disturbances in maternal hormone levels, immune health, anatomical interference, or a variety of maternal health conditions.¹⁶